Role of autophagy in neurodegenerative diseases

The growing range of implications of autophagy in a myriad of human physiological and pathological conditions has witnessed an exponential increase in the number of studies published over the last decade. The role of autophagy to function predominantly as a cellular survival mechanism has been widely accepted over the last few years. It is an evolutionarily conserved protein degradation pathway for long-lived proteins and organelles, which contributes to tissue and energy homeostasis. Dysfunction of this process is associated with diverse human diseases, ranging from cancer, infectious diseases and myopathies to neurodegenerative diseases. This review focuses on the role of autophagy in neurodegenerative diseases, where in most instances the mutant aggregate-prone proteins are autophagy substrates. Some of these mutant proteins can impair autophagy and augment neurodegeneration. Stimulation of autophagy by chemical inducers enhances autophagic degradation of aggregate-prone proteins and protects against neurodegeneration in several models of neurodegenerative diseases. The small molecule autophagy enhancers are of paramount importance for future therapeutic studies in other disease conditions beyond neurodegeneration, and also offer great potential in the study of signalling pathways regulating autophagy.