A review of autophagy mechanism of statins in the potential therapy of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegeneration csharacterized by amyloid-beta (A beta) deposition and abnormally phosphorylated Tau protein aggregation. Autophagy, as an important cellular metabolic activity, is closely related to the production, secretion and clearance of A beta peptide and Tau phosphorylation level. Therefore, autophagy may become a potential target for AD treatment. A large number of molecules are involved in the mammalian target of rapamycin (mTOR)-dependent or mTOR-independent pathway of autophagy. More and more evidences show that statins can intervene autophagy by regulating the activity or expression level of autophagy-related proteins and genes. On the one hand, statins can induce autophagy through Sirtuinl (SIRT1), P21, nuclear P53 and adenylate activated protein kinase (AMPK). On the other hand, statins inhibit the mevalonate metabolism pathway, thereby interfering with the prenylation of small OTPases, leading to autophagy dysfunction. Statins can also reduce the levels of LAMP2 and dynein, destroying autophagy. In this review, we focused on the role of autophagy in AD and the autophagy mechanism of statins in the potential treatment of AD.