The connection between autophagy and Alzheimer’s disease
Nechushtai Lior, D. Chen, Frenkel Dan, Pinkas-Kramarski Ronit
Abstract
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease associated with accumulation of amyloid beta peptides and intracellular neurofibrillary tangles formed by hyperphosphorylated Tau. Autophagy, an evolutionarily conserved process of self-degradation and turnover of cellular constituents, is important for normal cell growth but may be defective in diseases. A growing body of data implies that autophagy strongly affects AD pathogenesis. Autophagy mediates degradation of damaged organelles and proteins as well as neurotoxic aggregates, by regulating their clearance. Thus, impaired autophagy may account for the accumulation of protein aggregates. Since AD is characterized by neuroinflammation, impaired mitochondrial and lysosomal functions, and the accumulation of protein aggregates, the roles of autophagy/mitophagy in Alzheimer's will be extensively evaluated. In the current review, we will discuss the connection between autophagy/mitophagy and Alzheimer's. It seems that Alzheimer-related proteins such as APOE4, TREM2, PSEN1/2, APP and Tau can regulate autophagy. In turn, depending on the cellular system and animal model, autophagy regulating proteins such as Atg7, BECN1, GSK3B, MAP1LC3B, SQSTM1, TFEB and VCP can affect AD progression as discussed. We will also describe the effect of sex and lifestyle impact on autophagy and AD. Finally, we will describe how the current knowledge may contribute to potential therapeutic strategies.