Figure 1.
Causal relationship between intellectual property management and the regional economic development (This graph was drawn by the author).
Citation: Georgia Theocharopoulou. The ubiquitous role of mitochondria in Parkinson and other neurodegenerative diseases[J]. AIMS Neuroscience, 2020, 7(1): 43-65. doi: 10.3934/Neuroscience.2020004
| [1] | Xinli Hu, Wenjie Qin, Marco Tosato . Complexity dynamics and simulations in a discrete switching ecosystem induced by an intermittent threshold control strategy. Mathematical Biosciences and Engineering, 2020, 17(3): 2164-2178. doi: 10.3934/mbe.2020115 |
| [2] | Yue Liu, Liming Chen, Han Luo, Yuzhao Liu, Yixian Wen . The impact of intellectual property rights protection on green innovation: A quasi-natural experiment based on the pilot policy of the Chinese intellectual property court. Mathematical Biosciences and Engineering, 2024, 21(2): 2587-2607. doi: 10.3934/mbe.2024114 |
| [3] | Liping Wu, Zhongyi Xiang . A study of integrated pest management models with instantaneous and non-instantaneous impulse effects. Mathematical Biosciences and Engineering, 2024, 21(2): 3063-3094. doi: 10.3934/mbe.2024136 |
| [4] | Hao Zhou, Xia Wang, Sanyi Tang . Global dynamics of non-smooth Filippov pest-natural enemy system with constant releasing rate. Mathematical Biosciences and Engineering, 2019, 16(6): 7327-7361. doi: 10.3934/mbe.2019366 |
| [5] | Hebing Zhang, Xiaojing Zheng . Invariable distribution of co-evolutionary complex adaptive systems with agent's behavior and local topological configuration. Mathematical Biosciences and Engineering, 2024, 21(2): 3229-3261. doi: 10.3934/mbe.2024143 |
| [6] | Fei Wang, Benhai Guo, Zixing Wang, Yuxin Wu . The impact of digital economy on the export competitiveness of China's manufacturing industry. Mathematical Biosciences and Engineering, 2023, 20(4): 7253-7272. doi: 10.3934/mbe.2023314 |
| [7] | Jie Bai, Xiunan Wang, Jin Wang . An epidemic-economic model for COVID-19. Mathematical Biosciences and Engineering, 2022, 19(9): 9658-9696. doi: 10.3934/mbe.2022449 |
| [8] | Baolin Kang, Xiang Hou, Bing Liu . Threshold control strategy for a Filippov model with group defense of pests and a constant-rate release of natural enemies. Mathematical Biosciences and Engineering, 2023, 20(7): 12076-12092. doi: 10.3934/mbe.2023537 |
| [9] | Yue Song, Yi Zhang, Song Yang, Na Li . Investigation on stability and controller design for singular bio-economic systems with stochastic fluctuations. Mathematical Biosciences and Engineering, 2021, 18(3): 2991-3005. doi: 10.3934/mbe.2021150 |
| [10] | Yue Liu, Chunying Ma, Zhehao Huang . Can the digital economy improve green total factor productivity? An empirical study based on Chinese urban data. Mathematical Biosciences and Engineering, 2023, 20(4): 6866-6893. doi: 10.3934/mbe.2023296 |
Intellectual property rights can greatly promote regional economic growth have been accepted by us. China has formulated a strategy of building an innovative nation to stimulate economic development. In the new era, in order to achieve a major breakthrough in national economy and promote regional economic growth, it is of great importance to tremendously promote technological progress and industrial upgrading by relying on intellectual property management. From the perspective of policy and specific analysis of the political system, we focus on researching the growth of regional economy of intellectual property investment, technology, market, enterprise and production organization, the influence of output analysis from innovation to the intellectual property rights and translated into innovative products and form innovation in market profits, thus promotes the benign cycle of regional economic growth. The central government, local governments and enterprises all consider independent innovation and intellectual property management as a breakthrough for transformation and upgrading. The improvement of intellectual property management has thus become an important means to develop regional economy. How to improve intellectual property management, the important factors involved in the process of intellectual property management on promoting economic growth and how intellectual property management promotes economic growth have become a concern of managers in various fields. Intellectual property management system is a complex processes to promote economic growth. By revealing the driving force and path of the function of the elements of intellectual property management, enterprises and governments can better improve intellectual property management, promote the output of high-value patents and the transformation and upgrading of industrial structure, so as to enhance the driving force of regional economic growth.
In recent years, there have been several outstanding studies in intellectual property management, such as focusing on intellectual property management system research and intellectual property management ability research. In the research of intellectual property management system, domestic and foreign scholars focus on the operation, collaboration and evolution of the system. In the early research, such research focuses on the research of intellectual property strategy. To study the composition of intellectual property strategic system, from the perspective of intellectual property operation [1], intellectual property strategic resources [2], the process [3] and content of strategic management [4], and emphasize the importance of strategic management thinking in the early stage of intellectual property. In terms of intellectual property management ability, domestic and foreign scholars focus on the composition of ability elements, ability performance, the evolution of ability and the relationship with the growth of enterprises, which fully proves the relationship between the driving force of intellectual property in economic development and economic growth.
Here are many factors to promote economic growth. It has been agreed by many scholars that effective intellectual property management can greatly promote economic growth. Such as foreign scholars Idris, Grossmann V, Steger T M. et al., thought intellectual property had a positive effect on economic growth. Many scholars analyzed the impact of intellectual property on the economy from the perspective of process, and verify this view by analyzing the impact of intellectual property management process on enterprises. By influencing the business process of enterprise knowledge innovation, labor quality and technology level, thus affecting the production function of the enterprise. Through the influence of micro mechanism, the new drive economic development mode transformationcite [5].This is from the micro level of analysis, combined with the changes in the factors of enterprise wealth creation, to analyze the dynamic relationship between the two. Taking the transformation and upgrading of industrial structure as a mediating variable, this paper empirically studies that intellectual property management can indirectly promote industrial green growth. This study uses the Malmquist-Luenberger index model to measure industrial green total factor productivity. This model can systematically analyze intellectual property management, industrial upgrading and economic growth under the same frameworkcite [6]. The above studies show that the elements of knowledge or intellectual property management have an impact on the operation mode and production efficiency of the micro subject through the role of the micro subject, and thus have an impact and effect on the economy. In this process, there are power balance and contest, resource allocation and integration, organizational structure adjustment, the use of new technology, and so on. This process is the focus of this study.
The core of intellectual property management performance evaluation is the design of index system, which comprehensively reflects the level of intellectual property development, coordination, operation and protection. It is significantly correlated with regional economic level, scientific research ability and intellectual property market competition [7]. Intellectual property rights protection is a hot issue related to performance. It is generally believed that the impact of intellectual property rights protection on regional economic growth depends on the technological level of a region and the world's cutting-edge technology. The intellectual property rights protection is positively correlated with regional economic growth when there is a small gap between a region's technological level and cutting-edge technology; otherwise, there is a negative correlation between the two [8]. The FDI intensity has a significant effect on international technology transfer mode [9]. There is a significant positive correlation between intellectual property resources and assets on regional economy, and intellectual property resources can significantly improve regional competitiveness. However, the spatial spillover effect of intellectual property resources is significantly negative, and the increase of intellectual property rights in some provinces has a significant inhibitory effect on the regional competitiveness of surrounding provinces, because spatial spillover effect inhibits the development of surrounding provinces to a certain extent, increase operating costs and hinder the promotion of their regional competitiveness [10], Intellectual property strategy has a significant positive effect on technological innovation performance [11].
In the above studies, the factors related to intellectual property, such as management, resources, assets or a process or link of intellectual property management, or the role of intellectual property protection in economy or performance, are generally studied with technology as an intermediary factor, indicating that technology, as an endogenous factor of economic growth, can effectively drive the positive effect of other factor endowments on economic growth. Furthermore, the impact of intellectual property on enterprises, regional economy or competitiveness is mainly derived from technological innovation, industrial structure upgrading and economic transformation, whether in terms of resource or management. Draw lessons from the ideas of the above scholars, this study is based on the perspective of intellectual property management, under the guidance of intellectual property strategy, with intellectual property input, application, output as a research path.From the macro government support for intellectual property and financial investment, government-industry cooperation and financial support are put into the research system.From the micro enterprise, intellectual property creation and output process is included in the system. In the intermediate link, the technology market and other trading factors are considered into the research system, then has built a research framework.
It is not a simple process for intellectual property management to promote regional economy, wherein technological innovation serves as a bridge between the two and plays an intermediary role in their relationship. It is a complicated economic operation process from intellectual property management, value realization to the promotion of regional economic growth, in which the transformation of knowledge innovation into intellectual property, the role of intellectual property on technological innovation, the transformation of technological innovation into products, and the ultimate realization of value increment are involved. This process is a unified organic whole, which facilitates the positive effect of intellectual property on economic growth. This is also a complex knowledge transformation process, in which various elements and subjects develop in a coordinated manner. This complex system can be divided into several subsystems, including knowledge innovation system, intellectual property development and management, operation management and intellectual property protection of intellectual property rights management subsystem, technology innovation system, value-added and implementation system. Each subject and element coordinate and support each other, forming a complete seamless docking system. In the process of system operation, the main body and elements are mutually coordinated and supported. In this complex system, the goals and directions of different subjects are inconsistent, so are the roles and responsibilities they assume in the subsystems. In addition, the composition of the relationship between various elements depends on the attitudes and abilities of different subjects, and the integration of elements depends on the coordination and operation abilities of the subjects, as there are both synchronous and transitive relationships between subsystems. In such a complex relationship, the interrelationship among these elements cannot be completely understood only by subjective understanding or analysis. Instead, tools and methods are required to get insights into the docking relationship between subjects. System Dynamics (SD) is a tool that helps us to systematically understand the feedback relationship among factors, analyze the interrelation and constraint relationship among factors, and discover the causality of interaction and influence. By studying the structure of the system and analyzing the force and resistance based on the close dependence between the system behavior and the internal mechanism, the root causes of the problems can be identified from the internal structure of the system, thus achieving the purpose of understanding the function of the system. System dynamics is used to analyze the driving effect of intellectual property on regional economy, mainly for the following reasons: 1) The realization of regional economic growth by intellectual property management is a complex dynamic system. The regional economic growth depends on the cooperation and resource allocation of the main body. Under such soft constraints, different management modes or changing cooperation modes will produce different effects and results. 2) The effect of intellectual property management on regional economic growth has a causal feedback relationship with path, and such relationship is interlinked with a complex structure. 3) It is a long process from input of intellectual property to its effect on regional economic growth. There is a time difference in this process, which depends on the chain process from intellectual property, technological innovation, innovation output and value realization. 4) The results are directly affected from intellectual property management, technological innovation and value realization where there are a large number of variables and high-order nonlinear systems. 5) A thorough understanding of the process and factors of complex process and chain results and the structural reasons behind them can explain why the government's decision-making behavior is related to the behavior and ideology of the subject.
The introduction of several intellectual property policies can promote the top-down attention to intellectual property strategy and the formulation of strategy. In recent years, the investment strategy in the intellectual property pledge financing has made particularly remarkable achievements in transforming the intellectual property development of knowledge and intellectual property into innovative assets. Regional economic development can promote the increase of financial funds in the field of intellectual property, the government attaches more attention to the development of intellectual property, actively build an intellectual property trading market, promote the transfer and transformation of intellectual property, so as to promote enterprises to obtain innovation profits. From the perspective of enterprises, the increase of strategic and capital investment significantly improves the innovation ability of enterprises, thus promoting the transformation of intellectual property rights and forming innovation benefits. The above constitute three closed causal rings that can explain the internal reasons and dynamic direction between intellectual property rights and economic development, which is the most powerful tool for systematic thinking. These relational rings are linked by multiple open feedback chains, forming three causal feedback loops. Fully considering the process of transforming intellectual property rights into economic growth and its hidden reasons, system dynamics is able to describe the results and causes of its dynamic changes, so as to provide reliable reference and basis for the government to improve intellectual property rights management and optimize operation mechanism.
The large-scale system for intellectual property to promote regional economic growth can be divided into three subsystems. The boundary of the system can be accurately determined, and variables closely related to modeling purpose can be integrated into the system. This complete system involves the application of intellectual property rights, the formation of technological innovation capabilities, the generation of innovative products, the realization of value added and the acquisition of innovative benefits, so as to promote regional economic growth. In this process, the system boundary is the whole process of generating and using intellectual property and promoting economic growth. This process is seamless that does not include the process of how invisible knowledge and explicit knowledge are used to form intellectual property rights, nor does it include the social impact and environmental protection of regional economy in the past, which are not discussed in this study.
The driving process of intellectual property management for economic growth involves multiple interrelated and interdependent subjects. In this process, subjects not only identify with each other in behavior, but also get familiar with each other's goals. There is also an economic game, in which the restructuring and distribution of interests are completed, which requires a contract to bind each other. The process of reaching agreement between the two parties implies that the main elements are required to achieve a certain goal, but the balance is temporary. Due to the change of external conditions or the principal under the premise of unclear responsibilities and obligations of both sides, there will be a lot of uncertain risks, which prevents the goal from being achieved to a certain extent and results in losses or even legal disputes and liabilities. The intellectual property management involves three main bodies, namely enterprise, government and school. From the perspective of enterprises, it involves its internal professional intellectual property management personnel, personnel from intellectual property administrative departments or intellectual property management centers of development zones and industrial agglomeration zones, supervisors of intellectual property offices in cities divided into districts and supervisors of administrative units. In the stage of technological innovation, the integration of industries, universities and research institutions mainly involves subjects such as universities, research institutions, enterprises and governments and activities such as technological application, communication, dissemination, transfer or commercialization. In addition to government and enterprises, it also involves financial institutions. In the stage of value realization, manufacturers will trade innovative products on the market, which will also involve enterprises, government and market players. The enterprises provide innovative products, and the demanders pay for them. The demanders can be enterprises or government. This transaction process is realized through the market, and market players are also the main participants.
From the perspective of system, intellectual property management and regional economic growth are affected by both internal and external factors, which can promote or hinder system operation. For example, capital investment and policies related to intellectual property will promote the transformation of intellectual property and regional economic growth. In addition, there are some negative factors, such as intellectual property theft and unfair market competition, which are all negative forces in the operation of this system.
(1) Implementation of intellectual property strategy. Since the implementation of the Outline of the National Intellectual Property Strategy in 2008 [12], remarkable achievements have been made in intellectual property management nationwide. The ownership of intellectual property has grown rapidly, and the quality of intellectual property has been greatly improved. Some high-value patents have gradually emerged. The awareness of intellectual property protection has been enhanced, business environment has been greatly improved, and the overall awareness of intellectual property rights has been significantly enhanced. The fundamental environment for intellectual property rights has been gradually consolidated. At the same time, the international exchange activities of intellectual property rights have been further standardized, the exchange and cooperation mechanism has been further improved, and the international influence has been significantly increased.
(2) Policy support. China's economic development requires the transformation of kinetic energy and the adjustment of industrial structure. The adjustment of industrial structure requires innovation and industrial integration to promote the emergence of new industries. The original institutional basis cannot no longer adapt to new industrial development and industrial structure adjustment. Produce mutations and structural upgrades [13]. The institutional basis includes various policies formulated by the government to realize economic and administrative functions, such as policies to stimulate market competition, government innovation support policies, financial policies, intellectual property protection policies, etc [14]. Government subsidies can effectively stimulate innovation in strategic emerging industries, and bring additional effects of guiding enterprises to tackle technical problems and encouraging external investors for enterprises' R & D. The government subsidy has the signal effect, which transmits the strategic direction of the national key development industries and the tendency of future policy changes to the market, thus changing R & D expenditure decision of enterprises and the investment behavior of external investors and further effectively guiding and promoting enterprises' own capital and diversified social capital to follow up R & D investment.
(3) Construction of the industry-university-research cooperation network. A variety of new organizations will emerge, forming a criss-crossing network in the process of industry-university-research cooperation, in order to achieve different purposes and adapt to the competitive environment. Such networks make up a dynamic process of self-organization and self-adaptation, and the pursuit of interests, resources or values by different subjects will make the networks change constantly. Cooperation network can help enterprises to utilize external resources and strengthen the core technologies for common benefits among all the network members [15]. The cooperation networks evolve dynamically to meet changes in user needs, technological environments, or national policies. The changing process of innovation network is accompanied by the dissemination of knowledge, the flow of personnel, resource re-allocation, choice of new coupling relationship in the cooperation between government, enterprises and academia, and the realization of organizational evolution by interacting with the environment. As cooperation gradually deepens and matures, network structure is relatively stable, synergistic effect will play a "multiple complementary" advantage to achieve multiplier effect.
(1) Intellectual property financing risks. The development of intellectual property requires a lot of funds to support technological innovation. However, due to the asymmetry of contract interests, enterprises lack corresponding financial support in the process of intellectual property creation. Financing has become the biggest obstacle in the creation of intellectual property, and the use of intellectual property pledge financing is an important means to obtain funds. The pledge of intellectual property involves many risks, such as complexity, value fluctuation and difficulty in disposal, which is undoubtedly a great challenge for the government and enterprises.
(2) Risks of intellectual property strategic selection. The highly uncertain market environment will have a huge impact on enterprises' R & D. The true value of intellectual property lies in that enterprises use it as a marketing strategy for value appreciation [16], research, development and growth [17]. In the era of knowledge economy, with the increase of environmental uncertainty, the acceleration of technology and product upgrading, and the increasing mobility of scientific and technological personnel, traditional intellectual property strategy on the basis of property control is difficult to maintain the original competitive advantage. Enterprises have a low ability to achieve comprehensive control of intellectual property. Therefore, in an uncertain environment, the formulation of intellectual property strategy is also faced with risks and uncertainties. Choosing the appropriate strategy is an important issue facing enterprises.
(3) Non-standardization and standardization of intellectual property management. To implement the strategy of intellectual property rights, intellectual property management has been significantly improved. However, people in different regions have different degrees of understanding of the importance of intellectual property management, and have different investments in intellectual property management, including systems, regulations and security systems. There is a lack of perfect intellectual property application system and norms. Even in companies with planned and systematic protection of intellectual property, intellectual property management departments fall into an awkward dilemma, usually upset with how to integrate corporate management as an indispensable link. And they are often regarded as looking for trouble and making trouble for other departments. Therefore, they cannot get effective support and cooperation in their work, which directly affects the efficiency and effect of intellectual property management.
(4) Spillover of knowledge. The "competition and cooperation relationship" among enterprises is widespread. In the process of project cooperation or implementation, enterprises' advantageous technologies and key skills will inevitably leak out, resulting in the leakage of intellectual property and the imbalance of intellectual property resource allocation. In addition, the proximity of geographical space, the frequent exchange and flow of scientific and technological personnel, and the exchange of scientific and technological information are all positive externalities. Without reasonable compensation, the enthusiasm and efficiency of enterprise cooperation will be affected.
Intellectual property management involves input, application, transformation and protection of intellectual property, where multiple subjects play roles in different processes. From the macro level, the input of intellectual property depends on the economic foundation and development status of local governments. The financial expenditure of economically developed regions requires more resources for the input of intellectual property. Therefore, the increased input of intellectual property will positively affect the output of intellectual property. From the micro level, enterprise's emphasis on intellectual property will be an important basis for their intellectual property strategy. No matter from investment, operation and conversion, manpower, materials, resources and financial resources should be arranged strictly according to the strategy. In order to encourage the development of intellectual property rights, intellectual property will be used to produce new products, promote technological innovation, seek innovation products and then traded on the market for innovative benefits. In the process of R & D investment, the coordination between enterprises, universities and government is promoted, and knowledge is transformed and enhanced in the coordination process, resulting in knowledge exchange. Enterprises pay attention to the research and development of key technologies for enterprise development and promote the increase of the ownership of core technology patents, which is how intellectual property rights are produced. In order to gain advantages, enterprises vigorously promote the industrialization of patented technology. By making profits in the market, the market value of intellectual property is realized. This is a Mosaic and interaction process between intellectual property management and enterprise technology innovation to realize the value of the process. The management process of intellectual property and the technological innovation of enterprises are a parallel and constantly interwoven process, and it is also how intellectual property promotes the technological innovation of enterprises. The influence of intellectual property management on technological innovation is also reflected in the following aspects: First, intellectual property management can promote technological innovation. To a certain extent, intellectual property management can provide guidance for technological innovation, lead enterprises to develop towards the expected direction, promote enterprises to allocate resources reasonably, and improve the efficiency of technological innovation. Second, intellectual property management is involved in the entire process of enterprise technology innovation and can integrate and motivate all kinds of innovative thinking. Technological innovation is the basis and premise of intellectual property management and intellectual property management is the extension and development of technological innovation, which complement each other. In addition, intellectual property management can also protect the technological innovation of enterprises to a certain extent, and intellectual property is the basis of continuous innovation.
Based on the above analysis, the following causal loop is formed:
Regional economic output value–government financial input–intellectual property management input–knowledge achievement stock–technology market transaction amount–transformation rate of scientific and technological achievements–new product sales revenue–innovation revenue–industrial output value–GDP growth rate–regional total output value.
The loop mainly reflects the importance of local government to intellectual property management, the level of intellectual property management and the impact of regional intellectual property on regional enterprises' technological innovation and regional gross output value.
Enterprises are constantly seeking technological innovation in the competition. First, the effective allocation and reasonable adaptation of innovative resources can promote the continuous diffusion of innovative technologies, and then realize the research and development of innovative products. The benefits of innovation have already been reflected in market transactions. In the industrial chain, upstream and downstream enterprises can imitate, track and cooperate with innovative technologies and products to avoid being eliminated, which promotes a series of enterprises to continuously innovate technologies. In this process, it will be restricted by market factors. The higher the degree of marketization, the more attention will be paid to market signals and price evolution, and the more fierce competition among enterprises. In the fierce market competition mechanism, in order to survive and develop, enterprises continue to invest capital and manpower, innovation technology, in order to maintain industrial competitive advantages and industrial chain competitive position. In the process of continuous technological innovation, new products, new services and new processes are introduced and traded in the market so as to obtain high monopoly profits of new technologies. From the market perspective, industrial chain enterprises are constantly innovating, and some enterprises have made major breakthroughs in technological innovation with the technological innovation cooperation between upstream and downstream enterprises as a driving force. Some enterprises have even left the industrial chain to form new competitive technologies and products. In pursuing of technological innovation system, In the pursuit of technological innovation system, the innovation ability of the whole industry and enterprises rises to a new height, which promotes the industrial upgrading and improves the innovation ability and performance of the whole region. Based on the above analysis, the following causal loop is formed:
Ⅰ. (technological innovation driving force–industry-university-research cooperation (effectiveness of industry-university-research cooperation and degree of collaboration with small and medium-sized enterprises)–innovation risk–R & D input–sales revenue of new product invested by enterprise innovation factors–revenue of enterprise T–innovation revenue).
This loop mainly reflects the strength of technological innovation motivation of universities, scientific research institutions and enterprises, which are the main innovation subjects of industry, university and research, and the influence of enterprises' ability to carry out technological innovation activities on the regional total output value.
Ⅱ. (intellectual property strategy–policy support–intellectual property pledge financing capacity–market purchasing power–new product market demand–innovation impetus–enterprise innovation factor input–new product–new product sales revenue–innovation income).
The loop mainly reflects the degree to which the government attaches importance to intellectual property management and the ability to obtain innovation benefits considering market factors, such as policy support, intellectual property pledge financing etc. Considering the market environment, the influence of technological innovation level on regional total output value is also considered. The objective is to emphasize the importance of implementation of intellectual property strategy and government policy support.
Analyzing the above driving mechanism, we can conclude that the system of intellectual property rights for the regional economic growth consists of three subsystems: intellectual property management system, technology innovation driving system and government policy supporting driving system. The intellectual property management system consists of two parts. One is regional intellectual property management system, which leads the development of regional intellectual property, including intellectual property system, culture, intellectual property strategy, etc. The government, enterprises, research institutes and intermediary organizations are main bodies of this system. The other is enterprises' intellectual property management system, namely internal intellectual property management mechanism, self-organization system and intellectual property strategy. The technology innovation system includes both the large system of government, industry, university and research, and enterprise technology innovation system. The large system and the micro main body system interweave with each other, forming a close technical innovation cooperation network, and acting on the regional economic system at the same time. Therefore, these three systems are all open systems that interact with each other. Each subsystem is closely connected, driven and connected with each other. There is also a close coordination and cooperative operation relationship between systems, thus forming a powerful cooperative dynamic network system. The system power network is a dynamic system. The change may be caused by changes in the direction and number of internal elements, or by changes in the external environment. The stability of the drive system is a close coupling between subsystems. The coupling mechanism between the two depends on the cooperation intention and the interest relationship between the subjects, and also on rational resource allocation and sound system culture.
Based on the above analysis, a causal diagram was established, as shown in Figure 1.
Using the system dynamics theory, the driving process of intellectual property management for regional economic growth was analyzed. Firstly, the system boundary was determined, and the driving force and resistance factors of intellectual property for economic growth were analyzed. From the perspective of intellectual property management process, the driving force and resistance factors restrict and function each other, forming an integrated system. This system is composed of three subsystems, which interact and restrict each other. Under the interaction of these three subsystems, intellectual property and economic growth simultaneously evolve. Using the research results of subsystem analysis, the following problems can be solved:
(1) Address the black box issues from intellectual property rights to regional economic growth. The whole system is divided into three closely connected subsystems. On the one hand, according to analysis, the whole process involves intellectual property rights, technological innovation and regional economic growth. On the other hand, it is based on the view that the macro environment acts on the micro subject level, the transformation of innovation benefits from technological innovation to new products is realized. In the long run, the government plays a leading and supporting role in the regional economic growth. Whether from the financial input, the construction of trading institutions or policy support, it plays a crucial role in the whole system.
(2) From the perspective of the whole system, enterprises' technological innovation plays an intermediary and realization role in intellectual property rights and regional economic growth. After all, intellectual property management ability is improved by transforming intellectual property into new products for innovative benefits and thus regional economic growth. In this link, the cooperation between enterprises, universities and research institutes, technology transfer and intellectual property atmosphere have a direct impact on enterprises. In addition, external market competition and market mechanism play a stimulating role on enterprises, stimulating them to continuously seek innovation in the competition.
(3) The three subsystems are interrelated and interdependent. It can be seen from the diagram of system dynamics that enterprises' technology innovation system is the link connecting the other two subsystems, and is also the key subject to achieve the goal. The other two subsystems analyze the effect of intellectual property rights on regional economic growth from different perspectives. Firstly, the government allocates and integrates resources from the perspective of human resources and property. In addition, in terms of government management, effective institutional arrangements should be made to stimulate the innovation potential of action subjects, accelerate the transfer and application of scientific and technological achievements, and promote technological progress and economic growth. The government should also introduce relevant science and technology policies as leverage to form effective coordination among science and technology departments, enterprises, universities, intermediary agencies and platform operators and establish online and offline technology market trading platforms. The government is also advised to provide a variety of technology docking activities to build a service platform for efficient technology and capital docking, a supporting platform for promoting the industrialization of scientific and technological achievements and a comprehensive service platform for promoting the transfer and transformation of technological achievements.
(4) Further, according to the above analysis of causality and circuit, build system dynamics model, establish equations, intellectual property to promote regional economic growth simulation and simulation, realize intellectual property to drive the key factors, dynamics between the key factors, determine the causal relationship between the key factors, grasp the causal degeneration, to control the operation results of intellectual property, promote regional economic development.
This work was supported by the National Social Science Foundation of China.16BZZ074.
The authors declare that they have no conflicts of interest to report regarding the present study.
| [1] | Gonatas N, Shy G (1965) Childhood myopathies with abnormal mitochondria. Proceedings of the Vth International Congress of Neuropathology 100: 606-612. |
| [2] |
Baron M, Kudin AP, Kunz WS (2007) Mitochondrial dysfunction in neurodegenerative disorders. Biochem Soc Trans 35: 1228-1231. doi: 10.1042/BST0351228
|
| [3] |
DiMauro S (2011) A history of mitochondrial diseases. J Inherit Metab Dis 34: 261-276. doi: 10.1007/s10545-010-9082-x
|
| [4] |
Mattson MP, Gleichmann M, Cheng A (2008) Mitochondria in neuroplasticity and neurological disorders. Neuron 60: 748-766. doi: 10.1016/j.neuron.2008.10.010
|
| [5] |
Federico A, Cardaioli E, Da Pozzo P, et al. (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 322: 254-262. doi: 10.1016/j.jns.2012.05.030
|
| [6] |
De Vos KJ, Grierson AJ, Ackerley S, et al. (2008) Role of axonal transport in neurodegenerative diseases. Annu Rev Neurosci 31: 151-173. doi: 10.1146/annurev.neuro.31.061307.090711
|
| [7] |
Chen H, Chan DC (2009) Mitochondrial dynamics–fusion, fission, movement, and mitophagy–in neurodegenerative diseases. Hum Mol Genet 18: R169-R176. doi: 10.1093/hmg/ddp326
|
| [8] |
Wang X, Su B, Zheng L, et al. (2009) The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease. J Neurochem 109: 153-159. doi: 10.1111/j.1471-4159.2009.05867.x
|
| [9] |
Büeler H (2009) Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson's disease. Exp Neurol 218: 235-246. doi: 10.1016/j.expneurol.2009.03.006
|
| [10] |
Park JS, Davis RL, Sue CM (2018) Mitochondrial dysfunction in Parkinson's disease: new mechanistic insights and therapeutic perspectives. Curr Neurol Neurosci Rep 18: 21. doi: 10.1007/s11910-018-0829-3
|
| [11] | Alexiou A, Vlamos P, Volikas K (2010) A Theoretical Artificial Approach on Reducing Mitochondrial Abnormalities in Alzheimer Disease. Proceedings of the 10th IEEE International Conference on Information Technology and Applications in Biomedicin IEEE, 1-4. |
| [12] |
Benard G, Karbowski M (2009) Mitochondrial fusion and division: regulation and role in cell viability. Semin Cell Dev Biol 20: 365-374. doi: 10.1016/j.semcdb.2008.12.012
|
| [13] |
Zorov DB, Vorobjev IA, Popkov VA, et al. (2019) Lessons from the Discovery of Mitochondrial Fragmentation (Fission): A Review and Update. Cells 8: 175. doi: 10.3390/cells8020175
|
| [14] |
Sheng ZH (2017) The interplay of axonal energy homeostasis and mitochondrial trafficking and anchoring. Trends Cell Biol 27: 403-416. doi: 10.1016/j.tcb.2017.01.005
|
| [15] |
Lin MY, Sheng ZH (2015) Regulation of mitochondrial transport in neurons. Expe Cell Res 334: 35-44. doi: 10.1016/j.yexcr.2015.01.004
|
| [16] |
Mishra P, Chan DC (2016) Metabolic regulation of mitochondrial dynamics. J Cell Biol 212: 379-387. doi: 10.1083/jcb.201511036
|
| [17] |
Dickey AS, Strack S (2011) PKA/AKAP1 and PP2A/Bβ2 regulate neuronal morphogenesis via Drp1 phosphorylation and mitochondrial bioenergetics. J Neurosci 31: 15716-15726. doi: 10.1523/JNEUROSCI.3159-11.2011
|
| [18] |
Kuznetsov AV, Hermann M, Saks V, et al. (2009) The cell-type specificity of mitochondrial dynamics. Int J Biochem Cell B 41: 1928-1939. doi: 10.1016/j.biocel.2009.03.007
|
| [19] |
Palmer CS, Osellame LD, Stojanovski D, et al. (2011) The regulation of mitochondrial morphology: intricate mechanisms and dynamic machinery. Cell Signal 23: 1534-1545. doi: 10.1016/j.cellsig.2011.05.021
|
| [20] |
Chen H, McCaffery JM, Chan DC (2007) Mitochondrial Fusion Protects against Neurodegeneration in the Cerebellum. Cell 130: 548-562. doi: 10.1016/j.cell.2007.06.026
|
| [21] |
Twig G, Elorza A, Molina AJ, et al. (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27: 433-446. doi: 10.1038/sj.emboj.7601963
|
| [22] |
Meeusen S, DeVay R, Block J, et al. (2006) Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1. Cell 127: 383-395. doi: 10.1016/j.cell.2006.09.021
|
| [23] |
Liesa M, Palacín M, Zorzano A (2009) Mitochondrial dynamics in mammalian health and disease. Physiol Rev 89: 799-845. doi: 10.1152/physrev.00030.2008
|
| [24] |
Alexander C, Votruba M, Pesch U, et al. (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet 26: 211-215. doi: 10.1038/79944
|
| [25] |
Detmer S, Chan D (2007) Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 8: 870-879. doi: 10.1038/nrm2275
|
| [26] | Ono T, Isobe K, Nakada K, et al. (2001) Human cells are protected from mitochondrial dysfunction by complementation of DNA products in fused mitochondria. Exp Neurol 28: 272-275. |
| [27] |
Delettre C, Lenaers G, Griffoin JM, et al. (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 26: 207-210. doi: 10.1038/79936
|
| [28] |
Hudson G, Amati-Bonneau P, Blakely EL, et al. (2008) Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain 131: 329-337. doi: 10.1093/brain/awm272
|
| [29] |
Uo T, Dworzak J, Kinoshita C, et al. (2009) Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neurons. Exp Neurol 218: 274-285. doi: 10.1016/j.expneurol.2009.05.010
|
| [30] |
Ishihara N, Nomura M, Jofuku A, et al. (2009) Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat Cell Biol 11: 958-966. doi: 10.1038/ncb1907
|
| [31] |
Darshi M, Mendiola VL, Mackey MR, et al. (2011) ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function. J Biol Chem 286: 2918-2932. doi: 10.1074/jbc.M110.171975
|
| [32] |
Koch A, Yoon Y, Bonekamp NA, et al. (2005) A Role for Fis1 in Both Mitochondrial and Peroxisomal Fission in Mammalian Cells. Mol Biol Cell 16: 5077-5086. doi: 10.1091/mbc.e05-02-0159
|
| [33] |
Serasinghe M, Yoon Y (2008) The mitochondrial outer membrane protein hFis1 regulates mitochondrial morphology and fission through self-interaction. Exp Cell Res 314: 3494-3507. doi: 10.1016/j.yexcr.2008.09.009
|
| [34] |
Otera H, Wang C, Cleland MM, et al. (2010) Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J Cell Biol 191: 1141-1158. doi: 10.1083/jcb.201007152
|
| [35] |
Knott AB, Perkins G, Schwarzenbacher R, et al. (2008) Mitochondrial fragmentation in neurodegeneration. Nat Rev Neurosci 9: 505-518. doi: 10.1038/nrn2417
|
| [36] |
Niemann A, Ruegg M, Padula VL, et al. (2005) Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot-Marie-Tooth disease. J Cell Biol 170: 1067-1078. doi: 10.1083/jcb.200507087
|
| [37] |
Wagner KM, Rüegg M, Niemann A, et al. (2009) Targeting and function of the mitochondrial fission factor GDAP1 are dependent on its tail-anchor. PloS One 4: e5160. doi: 10.1371/journal.pone.0005160
|
| [38] |
Chen H, Detmer SA, Ewald AJ, et al. (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160: 189-200. doi: 10.1083/jcb.200211046
|
| [39] |
Wakabayashi J, Zhang Z, Wakabayashi N, et al. (2009) The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J Cell Biol 186: 805-816. doi: 10.1083/jcb.200903065
|
| [40] |
Chu CT (2019) Mechanisms of selective autophagy and mitophagy: Implications for neurodegenerative diseases. Neurobiol Dis 122: 23-34. doi: 10.1016/j.nbd.2018.07.015
|
| [41] |
Kageyama Y, Zhang Z, Roda R, et al. (2012) Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J Cell Biol 197: 535-551. doi: 10.1083/jcb.201110034
|
| [42] |
Lutz AK, Exner N, Fett ME, et al. (2009) Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem 284: 22938-22951. doi: 10.1074/jbc.M109.035774
|
| [43] |
Matsuda N, Sato S, Shiba K, et al. (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189: 211-221. doi: 10.1083/jcb.200910140
|
| [44] |
Narendra DP, Jin SM, Tanaka A, et al. (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8: e1000298. doi: 10.1371/journal.pbio.1000298
|
| [45] |
Zhu J, Dagda RK, CHu CT (2011) Monitoring mitophagy in neuronal cell cultures. Methods Mol Biol 793: 325-339. doi: 10.1007/978-1-61779-328-8_21
|
| [46] |
Knott AB, Bossy-Wetzel E (2009) Impairing the Mitochondrial Fission and Fusion Balance: A New Mechanism of Neurodegeneration. Ann N Y Acad Sci 1147: 283-292. doi: 10.1196/annals.1427.030
|
| [47] |
Martin LJ (2010) Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases. Pharmaceuticals 3: 839-915. doi: 10.3390/ph3040839
|
| [48] |
Corrado M, Scorrano L, Campello S (2012) Mitochondrial Dynamics in Cancer and Neurodegenerative and Neuroinflammatory Disease. Int J Cell Biol 2012. doi: 10.1155/2012/729290
|
| [49] |
Su B, Wang X, Zheng L, et al. (2010) Abnormal mitochondrial dynamics and neurodegenerative diseases. Biochim Biophys Acta 1802: 135-142. doi: 10.1016/j.bbadis.2009.09.013
|
| [50] |
Dauer W, Przedborski S (2003) Parkinson's disease: mechanisms and models. Neuron 39: 889-909. doi: 10.1016/S0896-6273(03)00568-3
|
| [51] |
Chang D, Nalls MA, Hallgrmsdóttir IB, et al. (2017) A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci. Nat Genet 49: 1511. doi: 10.1038/ng.3955
|
| [52] |
Olanow C, Tatton W (1999) Etiology and pathogenesis of Parkinson's disease. Annu Rev Neurosci 22: 123-144. doi: 10.1146/annurev.neuro.22.1.123
|
| [53] |
Koh H, Chung J (2010) PINK1 and Parkin to control mitochondria remodeling. Anat Cell Biol 43: 179-184. doi: 10.5115/acb.2010.43.3.179
|
| [54] |
Narendra D, Tanaka A, Suen DF, et al. (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183: 795-803. doi: 10.1083/jcb.200809125
|
| [55] |
Billingsley KJ, Barbosa IA, Bandrés-Ciga S, et al. (2019) Mitochondria function associated genes contribute to Parkinson's Disease risk and later age at onset. NPJ Parkinson's Dis 5: 8. doi: 10.1038/s41531-019-0080-x
|
| [56] |
Panayiotou C, Solaroli N, Johansson M, et al. (2010) Evidence of an intact N-terminal translocation sequence of human mitochondrial adenylate kinase 4. Int J Biochem Cell Biol 42: 62-69. doi: 10.1016/j.biocel.2009.09.007
|
| [57] |
Sai Y, Zou Z, Peng K, et al. (2012) The Parkinson's disease-related genes act in mitochondrial homeostasis. Neurosci Biobehav Rev 36: 2034-2043. doi: 10.1016/j.neubiorev.2012.06.007
|
| [58] |
Perier C, Vila M (2012) Mitochondrial biology and Parkinson's disease. Cold Spring Harb Perspect Med 2: a009332. doi: 10.1101/cshperspect.a009332
|
| [59] |
Comellas G, Lemkau LR, Nieuwkoop AJ, et al. (2011) Structured regions of α-synuclein fibrils include the early-onset Parkinson's disease mutation sites. J Mol Biol 411: 881-895. doi: 10.1016/j.jmb.2011.06.026
|
| [60] |
Ulmer TS, Bax A (2005) Comparison of structure and dynamics of micelle-bound human α-synuclein and Parkinson disease variants. J Biol Chem 280: 43179-43187. doi: 10.1074/jbc.M507624200
|
| [61] |
Nakamura K, Nemani VM, Azarbal F, et al. (2011) Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein α-synuclein. J Biol Chem 286: 20710-20726. doi: 10.1074/jbc.M110.213538
|
| [62] |
Mori H, Kondo T, Yokochi M, et al. (1998) Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q. Neurology 51: 890-892. doi: 10.1212/WNL.51.3.890
|
| [63] |
Mizuno Y, Hattori N, Yoshino H, et al. (2006) Progress in familial Parkinson's disease. Parkinson's Disease and Related Disorders Springer, 191-204. doi: 10.1007/978-3-211-45295-0_30
|
| [64] |
Lodi R, Tonon C, Valentino M, et al. (2004) Deficit of in vivo mitochondrial ATP production in OPA1-related dominant optic atrophy. Ann Neurol 56: 719-723. doi: 10.1002/ana.20278
|
| [65] |
Mayorov V, Lowrey A, Biousse V, et al. (2008) Mitochondrial oxidative phosphorylation in autosomal dominant optic atrophy. BMC Biochem 9: 22. doi: 10.1186/1471-2091-9-22
|
| [66] |
Zanna C, Ghelli A, Porcelli AM, et al. (2008) OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain 131: 352-367. doi: 10.1093/brain/awm335
|
| [67] | Krajewski K, Lewis R, Fuerst D, et al. (2000) Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A. Brain 44: 1299-1304. |
| [68] |
Berger P, Young P, Suter U (2002) Molecular cell biology of Charcot-Marie-Tooth disease. Neurogenetics 4: 1-15. doi: 10.1007/s10048-002-0130-z
|
| [69] |
Baloh R, Schmidt R, Pestronk A, et al. (2007) Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. J Neurosci 27: 422-430. doi: 10.1523/JNEUROSCI.4798-06.2007
|
| [70] |
Züchner S, Vance J (2006) Molecular genetics of autosomal-dominant axonal Charcot-Marie-Tooth disease. Neuromolecular Med 8: 63-74. doi: 10.1385/NMM:8:1-2:63
|
| [71] | Sme F (2010) MFN2 mutations cause severe phenotypes in most patients with CMT2A. Neurology 125: 245-256. |
| [72] |
Cerveny K, Tamura Y (2007) Regulation of mitochondrial fusion and division. Trends Cell Biol 17: 563-569. doi: 10.1016/j.tcb.2007.08.006
|
| [73] |
Poole AC, Thomas RE, Andrews LA, et al. (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 105: 1638-1643. doi: 10.1073/pnas.0709336105
|
| [74] |
Yang Y, Ouyang Y, Yang L, et al. (2008) Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci U S A 105: 7070-7075. doi: 10.1073/pnas.0711845105
|
| [75] |
Valente EM, Abou-Sleiman PM, Caputo V, et al. (2004) Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304: 1158-1160. doi: 10.1126/science.1096284
|
| [76] |
Rothfuss O, Fischer H, Hasegawa T, et al. (2009) Parkin protects mitochondrial genome integrity and supports mitochondrial DNA repair. Hum Mol Genet 18: 3832-3850. doi: 10.1093/hmg/ddp327
|
| [77] |
Mortiboys H, Thomas KJ, Koopman WJ, et al. (2008) Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Ann Neurol 64: 555-565. doi: 10.1002/ana.21492
|
| [78] |
Büttner S, Bitto A, Ring J, et al. (2008) Functional mitochondria are required for α-synuclein toxicity in aging yeast. J Biol Chem 283: 7554-7560. doi: 10.1074/jbc.M708477200
|
| [79] |
Banerjee K, Sinha M, Pham CLL, et al. (2010) α-Synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: Implications in Parkinson's disease. FEBS Lett 584: 1571-1576. doi: 10.1016/j.febslet.2010.03.012
|
| [80] |
Yao C, El Khoury R, Wang W, et al. (2010) LRRK2-mediated neurodegeneration and dysfunction of dopaminergic neurons in a Caenorhabditis elegans model of Parkinson's disease. Neurobiol Dis 40: 73-81. doi: 10.1016/j.nbd.2010.04.002
|
| [81] |
Wang X, Yan MH, Fujioka H, et al. (2012) LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1. Hum Mol Genet 21: 1931-1944. doi: 10.1093/hmg/dds003
|
| [82] |
Pich S, Bach D, Briones P, et al. (2005) The Charcot–Marie–Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet 14: 1405-1415. doi: 10.1093/hmg/ddi149
|
| [83] |
Detmer SA, Chan DC (2007) Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations. J Cell Biol 176: 405-414. doi: 10.1083/jcb.200611080
|
| [84] |
Niemann A, Berger P, Suter U (2006) Pathomechanisms of Mutant Proteins in Charcot-Marie-Tooth Disease. NeuroMolecular Med 8: 217-242. doi: 10.1385/NMM:8:1-2:217
|
| [85] |
Noack R, Frede S, Albrecht P, et al. (2012) Charcot–Marie–Tooth disease CMT4A: GDAP1 increases cellular glutathione and the mitochondrial membrane potential. Hum Mol Genet 21: 150-162. doi: 10.1093/hmg/ddr450
|
| [86] |
Cho D, Nakamura T, Fang J, et al. (2009) S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 324: 102-105. doi: 10.1126/science.1171091
|
| [87] |
Olichon A, Baricault L, Gas N (2003) Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J Biol Chem 278: 7743-7746. doi: 10.1074/jbc.C200677200
|
| [88] |
Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443: 787. doi: 10.1038/nature05292
|
| [89] |
Wang X, Wang W, Li L, et al. (2014) Oxidative stress and mitochondrial dysfunction in Alzheimer's disease. Biochim Biophys Acta 1842: 1240-1247. doi: 10.1016/j.bbadis.2013.10.015
|
| [90] |
Smith MA, Rottkamp CA, Nunomura A, et al. (2000) Oxidative stress in Alzheimer's disease. Biochim Biophys Acta 1502: 139-144. doi: 10.1016/S0925-4439(00)00040-5
|
| [91] |
Hirai K, Aliev G, Nunomura A, et al. (2001) Mitochondrial abnormalities in Alzheimer's disease. J Neurosci 21: 3017-3023. doi: 10.1523/JNEUROSCI.21-09-03017.2001
|
| [92] |
Sun A, Chen Y (1998) Oxidative stress and neurodegenerative disorders. J Biomed Sci 5: 401-414. doi: 10.1007/BF02255928
|
| [93] |
Islam MT (2017) Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 39: 73-82. doi: 10.1080/01616412.2016.1251711
|
| [94] |
Wang X, Su B, Fujioka H, et al. (2008) Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients. Am J Pathol 173: 470-482. doi: 10.2353/ajpath.2008.071208
|
| [95] |
Wang X, Su B, Siedlak SL, et al. (2008) Amyloid-β overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci 105: 19318-19323. doi: 10.1073/pnas.0804871105
|
| [96] |
Martin M, Hurd D, Saxton W (1999) Kinesins in the nervous system. Cell Mol Life Sci 56: 200-216. doi: 10.1007/s000180050422
|
| [97] |
Schnapp BJ, Reese TS (1989) Dynein is the motor for retrograde axonal transport of organelles. Proc Natl Acad Sci U S A 86: 1548-1552. doi: 10.1073/pnas.86.5.1548
|
| [98] | Tabb JS, Molyneaux BJ, Cohen DL, et al. (1998) Transport of ER vesicles on actin filaments in neurons by myosin V. J Cell Sci 111: 3221-3234. |
| [99] |
Ligon LA, Steward O (2000) Role of microtubules and actin filaments in the movement of mitochondria in the axons and dendrites of culture hippocampal neurons. Journal Comp Neur 427: 351-361. doi: 10.1002/1096-9861(20001120)427:3<351::AID-CNE3>3.0.CO;2-R
|
| [100] |
Hirokawa N (1998) Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279: 519-526. doi: 10.1126/science.279.5350.519
|
| [101] |
Gross SP (2004) Hither and yon: A review of bi-directional microtubule-based transport. Phys Biol 1: R1-R11. doi: 10.1088/1478-3967/1/2/R01
|
| [102] |
Ligon LA, Tokito M, Finklestein JM, et al. (2004) A direct interaction between cytoplasmic dynein and kinesin I may coordinate motor activity. J Biol Chem 279: 19201-19208. doi: 10.1074/jbc.M313472200
|
| [103] |
Stowers R, Megeath L, Górska-Andrzejak J, et al. (2002) Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron 36: 1063-1077. doi: 10.1016/S0896-6273(02)01094-2
|
| [104] |
Guo X, Macleod G, Wellington A, et al. (2005) The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron 47: 379-393. doi: 10.1016/j.neuron.2005.06.027
|
| [105] |
Russo G, Louie K, Wellington A, et al. (2009) Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport. J Neurosci 29: 5443-5455. doi: 10.1523/JNEUROSCI.5417-08.2009
|
| [106] |
Koutsopoulos OS, Laine D, Osellame L, et al. (2010) Human miltons associate with mitochondria and induce microtubule-dependent remodeling of mitochondrial networks. Biochim Biophys Acta 1803: 564-574. doi: 10.1016/j.bbamcr.2010.03.006
|
| [107] |
Wang X, Winter D, Ashrafi G, et al. (2011) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147: 893-906. doi: 10.1016/j.cell.2011.10.018
|
| [108] |
Hsieh CH, Shaltouki A, Gonzalez AE, et al. (2016) Functional impairment in miro degradation and mitophagy is a shared feature in familial and sporadic Parkinson's disease. Cell Stem Cell 19: 709-724. doi: 10.1016/j.stem.2016.08.002
|
| [109] |
Baloh RH (2008) Mitochondrial dynamics and peripheral neuropathy. Neuroscientist 14: 12-18. doi: 10.1177/1073858407307354
|
| [110] |
Misko A, Jiang S, Wegorzewska I, et al. (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30: 4232-4240. doi: 10.1523/JNEUROSCI.6248-09.2010
|
| [111] |
Ikenaka K, Katsuno M, Kawai K, et al. (2012) Disruption of axonal transport in motor neuron diseases. Int J Mol Sci 13: 1225-1238. doi: 10.3390/ijms13011225
|
| [112] |
Mandal A, Drerup CM (2019) Axonal transport and mitochondrial function in neurons. Front Cell Neurosci 13: 373. doi: 10.3389/fncel.2019.00373
|
| [113] |
Ader NR (2016) Seeking an in vivo neuronal context for the PINK1/Parkin pathway. J Neurosci 36: 11165-11167. doi: 10.1523/JNEUROSCI.2525-16.2016
|
| [114] |
Metaxakis A, Ploumi C, Tavernarakis N (2018) Autophagy in age-associated neurodegeneration. Cells 7: 37. doi: 10.3390/cells7050037
|
| [115] |
Rintoul GL, Reynolds IJ (2010) Mitochondrial trafficking and morphology in neuronal injury. Biochim Biophys Acta 1802: 143-150. doi: 10.1016/j.bbadis.2009.09.005
|
| [116] |
Chang DT, Reynolds IJ (2006) Mitochondrial trafficking and morphology in healthy and injured neurons. Prog Neurobiol 80: 241-268. doi: 10.1016/j.pneurobio.2006.09.003
|
| [117] |
Weihofen A, Thomas K, Ostaszewski B, et al. (2009) Pink1 forms a multiprotein complex with miro and milton, linking Pink1 function to mitochondrial trafficking. Biochemistry 48: 2045-2052. doi: 10.1021/bi8019178
|
| [118] |
Yang F, Jiang Q, Zhao J, et al. (2005) Parkin stabilizes microtubules through strong binding mediated by three independent domains. J Biol Chem 280: 17154-17162. doi: 10.1074/jbc.M500843200
|
| [119] |
Lee H, Khoshaghideh F, Lee S, et al. (2006) Impairment of microtubule-dependent trafficking by overexpression of α-synuclein. European J Neurosci 24: 3153-3162. doi: 10.1111/j.1460-9568.2006.05210.x
|
| [120] |
Gillardon F (2009) Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability—A point of convergence in Parkinsonian neurodegeneration? J Neurochem 10: 1514-1522. doi: 10.1111/j.1471-4159.2009.06235.x
|
| [121] |
Braak E, Sandmann-Keil D, Rüb U, et al. (2001) α-Synuclein immunopositive Parkinson's disease-related inclusion bodies in lower brain stem nuclei. Acta Neuropathol 101: 195-201. doi: 10.1007/s004010000247
|
| [122] |
Liu S, Sawada T, Lee S, et al. (2012) Parkinson's disease–associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet 8: e1002537. doi: 10.1371/journal.pgen.1002537
|
| [123] |
Chu Y, Morfini GA, Langhamer LB, et al. (2012) Alterations in axonal transport motor proteins in sporadic and experimental Parkinson's disease. Brain 135: 2058-2073. doi: 10.1093/brain/aws133
|
| [124] |
Abeliovich A, Gitler AD (2016) Defects in trafficking bridge Parkinson's disease pathology and genetics. Nature 539: 207. doi: 10.1038/nature20414
|
| [125] |
Züchner S, Mersiyanova I, Muglia M, et al. (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet 36: 449-451. doi: 10.1038/ng1341
|
| [126] |
Patzkó A, Shy ME (2011) Update on Charcot-Marie-Tooth Disease. Curr Neurol Neurosci Rep 11: 78-88. doi: 10.1007/s11910-010-0158-7
|
| [127] |
Shy M (2004) Charcot-Marie-Tooth disease: An update. Curr Opin Neurol 17: 579-585. doi: 10.1097/00019052-200410000-00008
|
| [128] |
Loiseau D, Chevrollier A, Verny C, et al. (2007) Mitochondrial coupling defect in Charcot–Marie–Tooth type 2A disease. Ann Neurol 61: 315-323. doi: 10.1002/ana.21086
|
| [129] |
Stokin G, Lillo C, Falzone T, et al. (2005) Axonopathy and transport deficits early in the pathogenesis of Alzheimer's diseases. Science 307: 1282-1288. doi: 10.1126/science.1105681
|
| [130] |
Wang X, Su B, Lee H (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J Neurosci 29: 9090-9103. doi: 10.1523/JNEUROSCI.1357-09.2009
|
| [131] |
Vickers JC, King AE, Woodhouse A, et al. (2009) Axonopathy and cytoskeletal disruption in degenerative diseases of the central nervous system. Brain Res Bull 80: 217-223. doi: 10.1016/j.brainresbull.2009.08.004
|
| [132] |
De Vos K, Chapman A, Tennant M, et al. (2007) Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum Mol Genet 16: 2720-2728. doi: 10.1093/hmg/ddm226
|
| [133] |
Shi P, Ström A, Gal J, et al. (2010) Effects of ALS-related SOD1 mutants on dynein- and KIF5-mediated retrograde and anterograde axonal transport. Biochim Biophys Acta 1802: 707-716. doi: 10.1016/j.bbadis.2010.05.008
|
| [134] |
Chang D, Rintoul G, Pandipati S, et al. (2006) Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis 22: 388-400. doi: 10.1016/j.nbd.2005.12.007
|
| [135] |
Trushina E, Dyer R, Badger J, et al. (2004) Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol Cell Biol 24: 8195-8209. doi: 10.1128/MCB.24.18.8195-8209.2004
|
| [136] |
Bach D, Pich S, Soriano FX (2003) Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism: a novel regulatory mechanism altered in obesity. J Biol Chem 278: 17190-17197. doi: 10.1074/jbc.M212754200
|
| [137] |
Chen H, Chomyn A, Chan DC (2005) Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 280: 26185-26192. doi: 10.1074/jbc.M503062200
|
| [138] |
Van Laar VS, Berman SB (2013) The interplay of neuronal mitochondrial dynamics and bioenergetics: implications for Parkinson's disease. Neurobiol Dis 51: 43-55. doi: 10.1016/j.nbd.2012.05.015
|
| [139] |
Coskun P, Wyrembak J, Schriner SE, et al. (2012) A mitochondrial etiology of Alzheimer and Parkinson disease. Biochim Biophys Acta 1820: 553-564. doi: 10.1016/j.bbagen.2011.08.008
|
| [140] |
Ryan BJ, Hoek S, Fon EA, et al. (2015) Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem Sci 40: 200-210. doi: 10.1016/j.tibs.2015.02.003
|
| [141] |
Van Laar VS, Berman SB (2009) Mitochondrial dynamics in Parkinson's disease. Exp Neurol 218: 247-256. doi: 10.1016/j.expneurol.2009.03.019
|
| [142] |
Requejo-Aguilar R, Bolaños JP (2016) Mitochondrial control of cell bioenergetics in Parkinson's disease. Free Radic Biol Med 100: 123-137. doi: 10.1016/j.freeradbiomed.2016.04.012
|
| [143] |
Abramov AY, Gegg M, Grunewald A, et al. (2011) Bioenergetic consequences of PINK1 mutations in Parkinson disease. PLoS One 6: e25622. doi: 10.1371/journal.pone.0025622
|
| [144] |
Lansbury PT, Lashuel HA (2006) A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature 443: 774-779. doi: 10.1038/nature05290
|
| [145] |
Jain S, Wood NW, Healy DG (2005) Molecular genetic pathways in Parkinson's disease: A review. Clin Sci 109: 355-364. doi: 10.1042/CS20050106
|
| [146] |
Winklhofer KF, Haass C (2010) Mitochondrial dysfunction in Parkinson's disease. Biochim Biophy Acta 1802: 29-44. doi: 10.1016/j.bbadis.2009.08.013
|
| [147] |
Chen C, Turnbull DM, Reeve AK (2019) Mitochondrial Dysfunction in Parkinson's Disease—Cause or Consequence? Biology 8: 38. doi: 10.3390/biology8020038
|
| [148] |
Diot A, Morten K, Poulton J (2016) Mitophagy plays a central role in mitochondrial ageing. Mamm Genome 27: 381-395. doi: 10.1007/s00335-016-9651-x
|
| [149] |
Noda S, Sato S, Fukuda T, et al. (2019) Loss of Parkin contributes to mitochondrial turnover and dopaminergic neuronal loss in aged mice. Neurobiol Dis 136: 104717. doi: 10.1016/j.nbd.2019.104717
|
| [150] |
Fivenson EM, Lautrup S, Sun N, et al. (2017) Mitophagy in neurodegeneration and aging. Neurochem Int 109: 202-209. doi: 10.1016/j.neuint.2017.02.007
|
| [151] |
Ebrahimi-Fakhari D, Wahlster L, McLean PJ (2012) Protein degradation pathways in Parkinson's disease: curse or blessing. Acta Neuropathol 124: 153-172. doi: 10.1007/s00401-012-1004-6
|
| [152] |
Wang W, Wang X, Fujioka H, et al. (2016) Parkinson's disease–associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes. Nat Med 22: 54. doi: 10.1038/nm.3983
|
| [153] |
Singleton A, Farrer M, Johnson J, et al. (2003) α-Synuclein locus triplication causes Parkinson's disease. Science 302: 841-841. doi: 10.1126/science.1090278
|
| [154] | Regev A, Silverman W, Shapiro E (2001) Representation and simulation of biochemical processes using the π-calculus process algebra. Pac Symp Biocomput 459-470. |
| [155] | Bonzanni N, Feenstra KA, Fokkink W, et al. (2009) What can formal methods bring to systems biology? International Symposium on Formal Methods Springer, 16-22. |
| [156] |
Theocharopoulou G, Giannakis K, Andronikos T (2015) The mechanism of splitting mitochondria in terms of membrane automata. 2015 IEEE International Symposium on Signal Processing and Information Technology (ISSPIT) IEEE, 397-402. doi: 10.1109/ISSPIT.2015.7394367
|
| [157] |
Theocharopoulou G, Vlamos P (2015) Modeling protein misfolding in Charcot–Marie–Tooth disease. GeNeDis 2014 Springer, 91-102. doi: 10.1007/978-3-319-09012-2_7
|
| [158] |
Theocharopoulou G, Bobori C, Vlamos P (2017) Formal models of biological systems. GeNeDis 2016 Springer, 325-338. doi: 10.1007/978-3-319-56246-9_27
|
| [159] |
Corona JC, Duchen MR (2015) Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets? J Bioenerg Biomembr 47: 89-99. doi: 10.1007/s10863-014-9576-6
|
| [160] |
Kitada T, Asakawa S, Hattori N, et al. (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392: 605. doi: 10.1038/33416
|
| [161] |
Healy DG, Falchi M, O'Sullivan SS, et al. (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol 7: 583-590. doi: 10.1016/S1474-4422(08)70117-0
|
| [162] |
Peng JY, Lin CC, Chen YJ, et al. (2011) Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics. PLoS Comput Biol 7: e1002212. doi: 10.1371/journal.pcbi.1002212
|
| [163] |
Tronstad KJ, Nooteboom M, Nilsson LI, et al. (2014) Regulation and quantification of cellular mitochondrial morphology and content. Curr Pharm Des 20: 5634-5652. doi: 10.2174/1381612820666140305230546
|
| [164] |
Zamponi N, Zamponi E, Cannas SA, et al. (2018) Mitochondrial network complexity emerges from fission/fusion dynamics. Sci Rep 8: 363. doi: 10.1038/s41598-017-18351-5
|
| [165] |
Shah SI, Paine JG, Perez C, et al. (2019) Mitochondrial fragmentation and network architecture in degenerative diseases. PloS One 14: e0223014. doi: 10.1371/journal.pone.0223014
|
| [166] |
Toglia P, Demuro A, Mak DOD, et al. (2018) Data-driven modeling of mitochondrial dysfunction in Alzheimer's disease. Cell Calcium 76: 23-35. doi: 10.1016/j.ceca.2018.09.003
|
| [167] |
Dukes AA, Bai Q, Van Laar VS, et al. (2016) Live imaging of mitochondrial dynamics in CNS dopaminergic neurons in vivo demonstrates early reversal of mitochondrial transport following MPP+ exposure. Neurobiol Dis 95: 238-249. doi: 10.1016/j.nbd.2016.07.020
|
| [168] | Alexiou A, Vlamos P (2012) Evidence for early identification of Alzheimer's disease. In arXiv preprint arXiv 1209.4223. |
| [169] |
Lundkvist J, Naslund J (2007) Gamma-secretase: A complex target for Alzheimer's disease. Curr Opin Pharmacol 7: 112-118. doi: 10.1016/j.coph.2006.10.002
|
| [170] |
Evin G, Kenche V (2007) BACE inhibitors as potential therapeutics for Alzheimer's disease. Recent Pat CNS Drug Discov 2: 188-199. doi: 10.2174/157488907782411783
|
| [171] |
Alexiou A, Vlamos P, Rekkas J (2011) Modeling the mitochondrial dysfunction in neurogenerative diseases due to high H+ concentration. Bioinformation 6: 173-175. doi: 10.6026/97320630006173
|
| [172] |
Miller KE, Sheetz MP (2004) Axonal mitochondrial transport and potential are correlated. J Cell Sci 117: 2791-2804. doi: 10.1242/jcs.01130
|
| [173] |
Oliveira JMA (2011) Techniques to investigate neuronal mitochondrial function and its pharmacological modulation. Curr Drug Targets 12: 762-773. doi: 10.2174/138945011795528895
|
| [174] |
Twig G, Hyde B, Shirihai OS (2008) Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta 1777: 1092-1097. doi: 10.1016/j.bbabio.2008.05.001
|
| [175] |
Onyango IG, Dennis J, Khan SM (2016) Mitochondrial dysfunction in Alzheimer's disease and the rationale for bioenergetics based therapies. Aging Dis 7: 201-214. doi: 10.14336/AD.2015.1007
|
| 1. | Haiyue Liu, Cangyu Wang, Qin Zhang, Changyi Zhao, Jie Jiang, The greening effects of regional innovation symbiosis – Evidence from Chinese listed firms, 2022, 0810-5391, 10.1111/acfi.13036 | |
| 2. | Yan Tan, Changyi Zhao, Nan Yang, J. Xu, A. Windapo, M.H.A. Hassan, A. Hajiyev, Research on The Evaluation Model of Symbiosis Degree in High-tech Industrial innovation Ecosystem-An Empirical Study Based on the Panel Data of China from 2012 to 2018, 2023, 409, 2267-1242, 01003, 10.1051/e3sconf/202340901003 | |
| 3. | He Yu, Tian Jiexin, Chen Zhenzhen, Qin Zhaohui, Mihasina Harinaivo Andrianarimanana, Influence of national intellectual property demonstration enterprise policy on urban green innovation: evidence from China, 2023, 1387-585X, 10.1007/s10668-023-03922-6 |
Figures(2) / Tables(2)
Georgia Theocharopoulou. The ubiquitous role of mitochondria in Parkinson and other neurodegenerative diseases[J]. AIMS Neuroscience, 2020, 7(1): 43-65. doi: 10.3934/Neuroscience.2020004
DownLoad:
