Phosphoproteomic analysis reveals the involvement of cyclin-dependent kinases in Corynoxine-induced

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:mxyyd
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  Parkinsons disease (PD), the second most common neurodegenerative disorder, is characterized by the accumulation of pathological protein aggregates (namely Lewy bodies) in dopaminergic neurons in the substantia nigra region of the brain.Alpha-synuclein (α-syn) is the major component of Lewy bodies in PD patients, and impairment of the autophagy-lysosomal system is proved to be linked to its accumulation.In our previous study, we identified corynoxine(Cory), a natural Chinese herbal compound, as an autophagy enhancer, which could clear wild type and mutant α-syn via autophagy.In this study, we firstly found that Cory induces autophagy in primary neurons and ameliorates the motor dysfunctions in a rotenone model of PD.Furthermore, to identify the signaling pathway(s) responsible for the pro-autophagic effect of Cory, we performed phosphoproteomic study.Kinases in the AKT and CDK families are among the top 10 connective kinases affected by Cory.Most of the top 10 connective substrates,such as HS90B, MAP1B, STMN1 and APC, could be phosphorylated by CDK family and involved in the autophagy progress.In the subnetworks analyzed by MCODE v1.4, CDK family closely connected with MAP1B and ABI2.All these data indicate that CDKs play important roles in Cory-induced autophagy.
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