Autophagy in neurodegenerative diseases and metal neurotoxicity

Autophagy generally refers to cell catabolic and recycling process in which cytoplasmic components are delivered to lysosomes for degradation. During the last two decades, autophagy research has experienced a recent boom because of a newfound connection between this process and many human diseases. Autophagy plays a significant role in maintaining cellular homeostasis and protects cells from varying insults, including misfolded and aggregated proteins and damaged organelles, which is particularly crucial in neuronal survival. Mounting evidence has implicated autophagic dysfunction in the pathogenesis of several major neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease and Huntington’s disease, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. In addition, autophagy has also been found to affect neurotoxicity induced by exposure to essential metals, such as manganese, copper, and iron, and other heavy metals, such as cadmium, lead, and methylmercury. This review examines current literature on the role of autophagy in the mechanisms of disease pathogenesis amongst common neurodegenerative disorders and of metal-induced neurotoxicity.