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Autophagy, a cellular protein degradation process, has been implicated in various human physiological and pathological conditions, such as development, immunity, cancer, neurodegeneration and longevity. It functions predominantly as a cell survival process during starvation, and is also critical for maintaining cellular homeostasis since tissue-specific abrogation of autophagy in normal mice causes dysfunction in the affected organs. While the mTOR pathway has been known to be the major regulator of autophagy, we have identified mTOR-independent autophagy pathways that are amenable to chemical perturbations. Several mutant aggregate-prone proteins associated with neurodegenerative diseases have been shown to be degraded by autophagy, and therefore, autophagy dysfunction occurring in such disease contexts may contribute to neurodegeneration by accumulating the toxic mutant species. Enhancing autophagy by small molecules is protective in a number of neurodegenerative disease models by facilitating the clearance of these mutant proteins. The chemical inducers of autophagy offer great potential as therapeutic targets not only in the context of neurodegeneration and diverse human diseases where autophagy acts as a protective pathway, but also for gaining mechanistic insights into the regulation of this process. In this talk, Sovan Sarkar will provide a brief overview of the regulation of autophagy and its implications in human diseases with particular emphasis on neurodegenerative diseases.
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