The role of autophagy in Alzheimer's disease and its potential for therapy

Abstract

Autophagy, the basic intracellular mechanism for catabolic and continuous clearance of unnecessary or dysfunctional components, occupies a crucial role in Alzheimer's disease (AD). Multiple studies both in vitro and in vivo have demonstrated that amyloid-β protein (Aβ) can be generated during autophagy, while lysosomal system is also directly implicated in the elimination of A β and tau protein. Pathophysically, both in AD models and AD patients, lysosomal dysfunction and autophagic vacuoles accumulation provide direct and objective evidence of impaired dynamic process of autophagy, which leads to the aggregation of Aβ and tau and thus contributes to the pathogenesis of AD. Accumulating studies in vivo have shown promising therapies targeting autophagic process, as activating autophagy may be beneficial to the early stages of AD and restoring lysosomal proteolysis may be favorable for the late stages of AD. This review mainly discusses the mechanism of autophagy-induced AD and the promising autophagy-related treatments for AD.

doi: 10.3969/j.issn.1672-6731.2014.05.015