| Description |
Autophagy, an intracellular degradation process, has been implicated in various physiological and pathological conditions, such as development, immunity, longevity, cancer, neurodegeneration. It plays a major role in the maintenance of cellular and energy homeostasis, and thus functions as a cell survival process. 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 aggregation-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. Recent data in autophagy-deficient human embryonic stem cell-derived neurons establish a causal link between autophagy deficiency and neurodegeneration. Enhancing autophagy by small molecules is protective in a number of neurodegenerative disease models, including induced pluripotent stem cell-based model of a lipid/lysosomal storage disorder. The chemical inducers of autophagy thus offer great potential as therapeutic candidates 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.
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