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.



    Alzheimer's disease



    Neurofibrillary Tangles


    Amyloid Precursor Protein


    soluble Amyloid Precursor Protein alpha


    Amyloid Precursor Protein Intra Cellular Domain


    N-Methyl-D-Aspartate Receptor


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


    nicotinic Acetylcholine Receptors


    muscarinic Acetylcholine Receptors


    soluble Amyloid Precursor Protein beta


    Reactive Oxygen Species


    Protein Kinase C


    Protein Kinase A


    Extracellular signal-Regulated Kinases2


    Cyclin-Dependent Kinases 5




    Cerebro Spinal Fluid


    Positron Emission Tomography


    Blood-Brain Barrier


    Physical Exercise


    Dementia with Lewy Bodies


    FrontoTemporal Dementia


    Magnetic Resonance Imaging


    functional Magnetic Resonance Imaging


    repetitive Transcranial Magnetic Stimulation


    transcranial Electrical Stimulation


    transcranial Direct Current Stimulation


    transcranial Alternating Current Stimulation


    transcranial Random Noise Stimulation


    transcranial Pulsed Current Stimulation


    Mild Cognitive Impairment


    Dynamin-related protein-1

    PSEN 1


    PSEN 2



    Insulin Degrading Enzyme


    Parkinson's Disease




    Protein Kinase B


    Glycogen synthase kinase 3α/β


    Electron Transport Chain


    Insulin-like Growth Factor-1




    Nitrous Oxide Synthase-2


    Nuclear Factor Kappa B


    Lipoprotein Receptor-related Protein-1






    G-Protein-Coupled Receptors


    Orexin Receptor-type-1


    Orexin Receptor-type-2


    Brain-Derived Neurotrophic Factor


    Obstructive Sleep Apnea (OSA)


    Central Disorders of Hypersomnolence


    Rapid Eye Movement




    Traumatic Brain Injury




    [11C]-Pittsburgh compound B


    Fluorine 18-labeled


    Montreal Cognitive Assessment


    Total tau




    Visinin-Like Protein


    Neuro Filament Light Protein


    Heart Fatty Acid Binding Protein


    Neuron-Specific Enolase


    Chitinase-3-like protein-1


    Tumor Necrosis Factor Ligand Superfamily member-10


    Angiotensin-Converting Enzyme




    Voxel-Based Morphometry


    Conflict of Interest

    The authors declare no conflict of interest.

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