(-) Schisandrin B enhances ATG16L1-mediated autophagy and promotes alpha-synuclein degradation in ne

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:anweiban
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  Autophagy is a major cellular machinery for the degradation of aggregated proteins via lysosome.Autophagy deregulation is closely associated with neurodegenerative and inflammatory disorders.Schisandrin B (SchB) is an active compound isolated from the commonly used Chinese herbal medicine Schisandra chinensis with anti-inflammatory and neuroprotective effects.In this study, we identified (-)SchB, a enantiomer of SchB as an autophagy enhancer.(-)SchB induced autophagy in neuronal cells including N2a, PC12 and SH-SY5Y, and in BV2 microglial cells.In PC12 cells overexpressing alpha-synuclein (SNCA),(-)SchB promoted the degradation of SNCA via autophagy.Interestingly, (-)SchB does not inhibit mTOR pathway or affect beclin 1 expression.By testing a series of autophagy genes by q-PCR, we found that the major genes upregulated by (-)SchB is ATG16L1.Furthermore, we confirmed that (-)SchB increased the protein level of ATG16L1 in several cell lines, thus promoting the formation of ATG5-ATG12/Atg16L1 complex.In conclusion, our study reveal that (-)SchB can enhance autophagy primarily by promoting Atg16L1-mediated autophagosome formation, which may account for its neuroprotective and anti-inflammatory effects.
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