Autophagy in Alzheimer’s disease pathogenesis: therapeutic potential and
Alzheimer’s disease (AD) is a complex neurodegenerative disease in the
elderly. It is the most common cause of dementia in human. AD is
characterized by accumulation of abnormal protein aggregates including
amyloid plaques (composed of beta-amyloid (Aβ) peptides) and
neurofibrillary tangles (formed by hyper-phosphorylated tau protein).
Besides, synaptic plasticity, neuroinflammation, calcium signaling etc.
are found to be dysfunctional as well in AD patients. Autophagy is an
evolutionarily conserved lysosome-dependent cellular event in
eukaryotes. It is closely linked to the modulation of protein
metabolism, through which damaged organelles and mis-folded proteins are
degraded and then recycled to maintain protein homeostasis. Accumulating
evidence has showed that impaired autophagy contributes to AD
pathogenesis. In the present review, we highlight the role of autophagy,
including bulk and selective autophagy, in regulating metabolic circuits
in AD pathogenesis. We also discuss the potential and future
perspectives of autophagy-inducing strategy in AD therapeutics.