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Role of nucleolar dysfunction in neurodegenerative disorders: a game of genes?

1 Institute of Applied Physiology, University of Ulm, Ulm, Germany;
2 Institute of Anatomy and Cell Biology, Department of Medical Biology, University of Heidelberg, Heidelberg, Germany;
3 Dept. of Molecular Biology of the Cell II, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany

Special Issues: Molecular Mechanisms of Neurodegenerative Diseases

Within the cell nucleus the nucleolus is the site of rRNA transcription and ribosome biogenesis and its activity is clearly essential for a correct cell function, however its specific role in neuronal homeostasis remains mainly unknown. Here we review recent evidence that impaired nucleolar activity is a common mechanism in different neurodegenerative disorders. We focus on the specific causes and consequences of impaired nucleolar activity to better understand the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). In particular, we discuss the genetic and epigenetic factors that might regulate nucleolar function in these diseases. In addition, we describe novel animal models enabling the dissection of the context-specific series of events triggered by nucleolar disruption, also known as nucleolar stress. Finally, we suggest how this novel mechanism could help to identify strategies to treat these still incurable disorders.
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Keywords nucleolus; cellular stress; rRNA; neurodegeneration; mouse models; epigenetic regulation

Citation: Rosanna Parlato, Holger Bierhoff. Role of nucleolar dysfunction in neurodegenerative disorders: a game of genes?. AIMS Molecular Science, 2015, 2(3): 211-224. doi: 10.3934/molsci.2015.3.211


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Copyright Info: 2015, Rosanna Parlato, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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