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• W2037156952 abstract "Abstract Our previous study has shown that PTEN ‐induced novel kinase 1 ( PINK 1 ) knocking down significantly induced mitochondrial fragmentation. Although PINK 1 is proved to be associated with autosomal recessive parkinsonism and its function in this chronic pathological process is widely studied, its role in acute energy crisis such as ischemic stroke is poorly known. In this study by employing an oxygen–glucose deprivation ( OGD ) neuronal model, we explored the function of PINK 1 in cerebral ischemia. Human PINK 1, two PINK 1 mutants W437X and K219M, or Pink1 sh RNA were transduced before OGD using lentiviral delivery. Our results showed that over‐expression of wild‐type PINK 1 significantly ameliorated OGD induced cell death and energy disturbance including reduced ATP generation and collapse of mitochondrial membrane potential. PINK 1 over‐expression also reversed OGD increased mitochondrial fragmentation, and suppressed the translocation of the mitochondrial fission protein dynamin‐related protein 1 (Drp1) from the cytosol to the mitochondria. Transduction of the mutant PINK 1 failed to provide any protective effect, while knockdown of Pink1 significantly increased the severity of OGD ‐induced neuronal damage. Importantly, inhibition of Drp1 reversed the effects of knocking down Pink1 on neuronal death and ATP production in response to OGD . This study demonstrates that PINK 1 prevents ischemic damage in neurons by attenuating mitochondrial translocation of Drp1, which maintains mitochondrial function and inhibits ischemia‐induced mitochondrial fission. These novel findings implicate a pivotal role of PINK 1 regulated mitochondrial dynamics in the pathology of ischemic stroke. image In this study by employing an oxygen–glucose deprivation (OGD) neuronal model, we explored the function of PINK1 in cerebral ischemia. We indicated that PINK1 significantly ameliorated OGD induced cell death and energy disturbance including reduced ATP generation and collapse of mitochondrial membrane potential by attenuating mitochondrial translocation of Drp1, which maintains mitochondrial function and inhibits ischemia‐induced mitochondrial fission." @default.
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• W2037156952 date "2013-07-01" @default.
• W2037156952 modified "2023-10-18" @default.
• W2037156952 title "The Parkinson's disease‐associated gene <i><scp>PINK</scp>1</i> protects neurons from ischemic damage by decreasing mitochondrial translocation of the fission promoter Drp1" @default.
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• W2037156952 doi "https://doi.org/10.1111/jnc.12340" @default.
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