ABSTRACT
Alzheimer’s disease (AD) is a neurodegenerative disease, β-amyloid (Aβ) deposition and Tau protein hyperphosphorylation are the main pathological features. Silent mating-type information regulation 2 homolog 1 (SIRT1) can deacetylate various types of histones and non-histones, and play an important role in the pathogenesis of AD. Recent studies found that exercise can activate SIRT1 to delay the progression of AD. The mechanisms may be as follows: inhibit the activity of β-secretase and increase the activity of α-secretase to reduce the production of Aβ; reduce the accumulation of hyperphosphorylated Tau protein; interact with PGC-1α to promote mitochondrial biogenesis; up-regulate PINK1/ Parkin signaling pathway to improve mitochondrial autophagy; and deacetylate NF-κB to inhibit neuroinflammation. In addition, the protein levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in hippocampus are increased, and ApoE4 gene is inhibited to enhance synaptic plasticity. This article summarizes the role and mechanisms of exercise in improving AD by regulating SIRT1, and provides new ideas for the prevention and treatment of AD.
ABSTRACT
Alzheimer' s disease (AD) is an age-related neurodegenerative disease which seriously damages the physical and mental health of the elderly and causes huge economic pressure to the society. However, the pathogenesis of AD is not completely elucidated. There is still no effective drug to cure AD in clinical practice. Tau protein is a soluble and non-aggregating microtubule-related protein, which can stabilize microtubule structure. The structure and function of Tau protein are abnormal in AD' s brain while under pathological conditions, and the abnormal Tau protein aggregates to insoluble neurofibrillary tangles which damages microtubules and leads to cognitive dysfunction. These changes of Tau protein are regulated by a variety of post-translational modifications, which directly change the properties and functions of proteins by attaching specific chemical moieties to Tau protein's C-terminus or N-terminus. It's confirmed that a variety of Tau post-translational modifications, like phosphorylation, glycosylation, acetylation and sumoylation is abnormal in AD's brain, which is closely related to Tau degradation and the accumulation of toxic substances. In this review, we summarized the latest progress supporting the role of exercise regulated Tau post-translational modification in the prevention and treatment of Alzheimer's disease. Firstly, exercise inhibits tau protein hyperphosphorylation by suppressing the activity of GSK-3β and MAPKs and possibly by up-regulating the activity of PP2A. Secondly, exercise increases tau protein O-GlcNAcylation by up-regulating the expression of GLUT1 and GLUT3, also possibly by regulating the balance of activity of OGT and OGA. Thirdly, exercise decreases tau protein acetylation possibly by inhibiting p300 and activating SIRT1; exercise regulates the acetylation of Tau KXGS possibly by inhibiting HDAC6. Lastly, exercise inhibits abnormal Tau sumoylation possibly by regulating the co-location sites of phosphorylation and sumoylation.