Role of autophagy in the pathogenesis of Alzheimer disease

Abstract

Alzheimer disease (AD) is the most common progressive neurodegenerative disorder causing increased morbidity and mortality. It is characterized by accumulation of amyloid-β in neurons. As there is no known definitive treatment of this disorder, studies trying to determine its exact pathogenetic pathways and target therapies for these specific pathways are being rapidly conducted. Autophagy is one of the areas of interest in studies on the pathogenesis of AD. It is a process of self-digestion that is thought to be a response to stressors and allows cells to adapt to environmental changes. There is accumulating evidence showing an association between autophagy and some disorders like cancer, infectious disease, and, in particular, neurodegenerative disorders. Growing attention has been focused on impaired autophagy in neurodegenerative disorders including AD, resulting in buildup of toxic molecules because of inappropriate activation of proteases or defective proteolysis. The question of whether autophagic response may be precisely modulated to prevent or treat neurodegenerative disorders like AD is still unanswered. In the future, it is thought that the autophagic process may be the one of the cornerstones of the treatment of AD. In this review, we summarize the knowledge of autophagy in the pathogenesis of AD in light of the current literature.