Review Special Issues

Molecular mechanisms in Alzheimer's disease and the impact of physical exercise with advancements in therapeutic approaches

  • Received: 18 December 2020 Accepted: 16 March 2021 Published: 19 March 2021
  • Alzheimer's disease (AD) is one of the most common, severe neurodegenerative brain disorder characterized by the accumulation of amyloid-beta plaques, neurofibrillary tangles in the brain causing neural disintegration, synaptic dysfunction, and neuronal death leading to dementia. Although many US-FDA-approved drugs like Donepezil, Rivastigmine, Galantamine are available in the market, their consumption reduces only the symptoms of the disease but fails in potency to cure the disease. This disease affects many individuals with aging. Combating the disease tends to be very expensive. This review focuses on biochemical mechanisms in the neuron both at normal and AD state with relevance to the tau hypothesis, amyloid hypothesis, the risk factors influencing dementia, oxidative stress, and neuroinflammation altogether integrated with neurodegeneration. A brief survey is carried out on available biomarkers in the diagnosis of the disease, drugs used for the treatment, and the challenges in approaching therapeutic targets in inhibiting the disease pathologies. This review conjointly assesses the demerits with the inefficiency of drugs to reach targets, their side effects, and toxicity. Optimistically, this review directs on the advantageous strategies in using nanotechnology-based drug delivery systems to cross the blood-brain barrier for improving the efficacy of drugs combined with a novel neuronal stem cell therapy approach. Determinately, this review aims at the natural, non-therapeutic healing impact of physical exercise on different model organisms and the effect of safe neuromodulation treatments using repetitive Transcranial Magnetic Stimulation (rTMS), transcranial Electrical Stimulation (tES) in humans to control the disease pathologies prominent in enhancing the synaptic function.

    Citation: Kiran Kumar Siddappaji, Shubha Gopal. Molecular mechanisms in Alzheimer's disease and the impact of physical exercise with advancements in therapeutic approaches[J]. AIMS Neuroscience, 2021, 8(3): 357-389. doi: 10.3934/Neuroscience.2021020

    Related Papers:

  • Alzheimer's disease (AD) is one of the most common, severe neurodegenerative brain disorder characterized by the accumulation of amyloid-beta plaques, neurofibrillary tangles in the brain causing neural disintegration, synaptic dysfunction, and neuronal death leading to dementia. Although many US-FDA-approved drugs like Donepezil, Rivastigmine, Galantamine are available in the market, their consumption reduces only the symptoms of the disease but fails in potency to cure the disease. This disease affects many individuals with aging. Combating the disease tends to be very expensive. This review focuses on biochemical mechanisms in the neuron both at normal and AD state with relevance to the tau hypothesis, amyloid hypothesis, the risk factors influencing dementia, oxidative stress, and neuroinflammation altogether integrated with neurodegeneration. A brief survey is carried out on available biomarkers in the diagnosis of the disease, drugs used for the treatment, and the challenges in approaching therapeutic targets in inhibiting the disease pathologies. This review conjointly assesses the demerits with the inefficiency of drugs to reach targets, their side effects, and toxicity. Optimistically, this review directs on the advantageous strategies in using nanotechnology-based drug delivery systems to cross the blood-brain barrier for improving the efficacy of drugs combined with a novel neuronal stem cell therapy approach. Determinately, this review aims at the natural, non-therapeutic healing impact of physical exercise on different model organisms and the effect of safe neuromodulation treatments using repetitive Transcranial Magnetic Stimulation (rTMS), transcranial Electrical Stimulation (tES) in humans to control the disease pathologies prominent in enhancing the synaptic function.


    Abbreviations

    AD

    Alzheimer's disease

    Amyloid-beta

    NFTs

    Neurofibrillary Tangles

    APP

    Amyloid Precursor Protein

    sAPPα

    soluble Amyloid Precursor Protein alpha

    AICD

    Amyloid Precursor Protein Intra Cellular Domain

    NMDAR

    N-Methyl-D-Aspartate Receptor

    AMPAR

    α-Amino-3-hydroxy-5-Methyl-4-isoxazole Propionic acid Receptor

    nAChRs

    nicotinic Acetylcholine Receptors

    mAChRs

    muscarinic Acetylcholine Receptors

    sAPPβ

    soluble Amyloid Precursor Protein beta

    ROS

    Reactive Oxygen Species

    PKC

    Protein Kinase C

    PKA

    Protein Kinase A

    ERK2

    Extracellular signal-Regulated Kinases2

    CDK5

    Cyclin-Dependent Kinases 5

    AchE

    AcetylcholinEsterase

    CSF

    Cerebro Spinal Fluid

    PET

    Positron Emission Tomography

    BBB

    Blood-Brain Barrier

    PE

    Physical Exercise

    DLB

    Dementia with Lewy Bodies

    FTD

    FrontoTemporal Dementia

    MRI

    Magnetic Resonance Imaging

    fMRI

    functional Magnetic Resonance Imaging

    rTMS

    repetitive Transcranial Magnetic Stimulation

    tES

    transcranial Electrical Stimulation

    tDCS

    transcranial Direct Current Stimulation

    tACS

    transcranial Alternating Current Stimulation

    tRNS

    transcranial Random Noise Stimulation

    tPCS

    transcranial Pulsed Current Stimulation

    MCI

    Mild Cognitive Impairment

    Drp1

    Dynamin-related protein-1

    PSEN 1

    Presenilin-1

    PSEN 2

    Presenilin-2

    IDE

    Insulin Degrading Enzyme

    PD

    Parkinson's Disease

    ApoE

    Apolipoprotein-E

    PKB

    Protein Kinase B

    GSK3α/β

    Glycogen synthase kinase 3α/β

    ETC

    Electron Transport Chain

    IGF-1

    Insulin-like Growth Factor-1

    IL-6

    Interleukin-6

    NOS-2

    Nitrous Oxide Synthase-2

    NF-κB

    Nuclear Factor Kappa B

    LRP-1

    Lipoprotein Receptor-related Protein-1

    OR-A

    Orexin-A

    OR-B

    Orexin-B

    GPCRs

    G-Protein-Coupled Receptors

    OX1R

    Orexin Receptor-type-1

    OX2R

    Orexin Receptor-type-2

    BDNF

    Brain-Derived Neurotrophic Factor

    OSA

    Obstructive Sleep Apnea (OSA)

    CDH

    Central Disorders of Hypersomnolence

    REM

    Rapid Eye Movement

    EEG

    Electroencephalogram

    TBI

    Traumatic Brain Injury

    123I-MIBG

    123I-Meta-IodoBenzylGuanidine

    [11C]PiB

    [11C]-Pittsburgh compound B

    18F

    Fluorine 18-labeled

    MoCA

    Montreal Cognitive Assessment

    T-tau

    Total tau

    P-tau

    phosphorylated-tau

    VLP-1

    Visinin-Like Protein

    NFL

    Neuro Filament Light Protein

    HFABP

    Heart Fatty Acid Binding Protein

    NSE

    Neuron-Specific Enolase

    CHI3L1

    Chitinase-3-like protein-1

    TNFSF10

    Tumor Necrosis Factor Ligand Superfamily member-10

    ACE

    Angiotensin-Converting Enzyme

    3xTg-AD

    triple-transgenic-AD

    VBM

    Voxel-Based Morphometry

    加载中


    Conflict of Interest



    The authors declare no conflict of interest.

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