Related Experiment Videos
Pink1 interacts with α-synuclein and abrogates α-synuclein-induced neurotoxicity by activating autophagy
Jia Liu1, Xue Wang1,2, Yongquan Lu1
1Center of Parkinson's Disease Beijing Institute for Brain Disorders, Beijing Key Laboratory on Parkinson's Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Center of Neural Regeneration and Repair, Department of Neurobiology Capital Medical University, Beijing 100069, China.
Abstract:
Parkinson's disease (PD) is one of the most common neurodegenerative diseases, characterized by degeneration of dopaminergic neurons in the substantia nigra. α-synuclein (α-syn) and PTEN-induced putative kinase (PINK)1 are two critical proteins associated with the pathogenesis of PD. α-syn induces mitochondrial deficits and apoptosis, PINK1 was found to alleviate α-syn-induced toxicity, but the mechanistic details remain obscure. Here, we show that PINK1 interacts with α-syn mainly in the cytoplasm, where it initiates autophagy. This interaction was dependent on the kinase activity of PINK1 and was abolished by deletion of the kinase domain or a G309D point mutation, an inactivating mutation in the kinase domain. Interaction between PINK1 and α-syn stimulated the removal of excess α-syn, which prevented mitochondrial deficits and apoptosis. Our findings provide evidence for a novel mechanism underlying the protective effects of PINK1 against α-syn-induced neurodegeneration and highlight a novel therapeutic target for PD treatment.