A30P mutant α-synuclein impairs autophagic flux by inactivating JNK signaling to enhance ZKSCAN3 activity in midbrain dopaminergic neurons.

ABSTRACT: Mutations in α-synuclein gene have been linked to familial early-onset Parkinson's disease (PD) with Lewy body pathology. A30P mutant α-synuclein is believed to suppress autophagic progression associated with PD pathogenesis. However, the mechanistic link between A30P mutation and autophagy inhibition in PD remains poorly understood. In this study, we identified that A30P mutant α-synuclein resulted in reduced autophagy flux through promoting the decrease of autophagosomal membrane-associated protein LC3 and the increase of SQSTM1/p62 protein levels in midbrain dopaminergic neuron, due to the transcriptional repressor ZKSCAN3 trafficking from the cytoplasm to the nucleus. Moreover, the results demonstrated that A30P mutant α-synuclein not only decreased the phospho-c-Jun N-terminal Kinase

SUBMITTER: Lei Z 

PROVIDER: S-EPMC6372582 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature