Identification and characterization of novel small molecules for their role in modulation of autopha

来源 :The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会 | 被引量 : 0次 | 上传用户:shensq
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  Autophagy is a process of self-cannibalization at the cellular level which involves sequestration of cytosolic components within a double membranous structure called the autophagosome, and their subsequent degradation in lysosomes.The main function of autophagy is to supply amino acids and lipids in response to starvation for new protein synthesis and energy.Autophagy is also involved in selectively degrading aggregated proteins, unnecessary or damaged organelles and intracellular pathogens.Autophagy also serves a neuroprotective role, and has been shown to be involved in heart diseases, atherosclerosis, certain myopathies, innate and adaptive immune responses, and cancer.Thus, genetic and pharmacological modulation of autophagy has been shown to be beneficial in many such situations.To study and understand the process of autophagy better we plan to use small molecule modulators as the tools.Towards this a high throughput luciferase assay as readout for autophagy has been established in a yeast model.Employing this assay, two small molecule libraries comprising of ~1800 compounds have been screened to identify "hits"-molecules that either up regulate or inhibit autophagy.These hits have been validated by secondary assays.Several of these hits have been characterised further to identify their role in autophagy regulation using yeast and mammalian models of autophagy.Results of two hits-one that blocks autophagy at an early stage of autophagy induction while another that acts at later stages, will be discussed.
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