The Mechanisms Of Parkinson’s Disease Via Parkin In Mitochondrial Stability

There is a relationship between parkin mutation and Parkinson’s disease (PD), because parkin as an E3 ubiquitin ligase, as well as the first proved protein is related to familial inheritance Parkinsonism. MPP+ as a neurotoxin can lead to mitochondrial dysfunction. Meanwhile, MPP+-induced neurotoxicity in cells is regared as the best model to research PD. This research aimed to investigate the neuroprotective effects and the mechanism of parkin in mice primary cells and PC12 cells upon MPP+ exist, as well as aim to understand the mechanism of mitochondrial dysfunction in PD. The main results are summaried as follows:(1) After cells in full brain, mesencephalon or hippocampus tissue treated with MPP+ for 24h, morphology of cells, the activity of Caspase-3 and the expression of parkin were measured. We found that the cells of mesencephalon are most sensitive to MPP+, and the expression of parkin in mesencephalon also decreased most in MPP+.(2) When treated with same concentration of MPP+, PC12 cells with parkin silence were more sensitive to MPP+ than normal PC12 cells. The changes of cell viability and the increase of a-synuclein were significant. We also proved that parkin was able to clear a-synuclein by ubiquitin proteasome pathway (UPP).(3) The neuroprotection of parkin in PC12 cells is relatd to mitochondrial apoptotic way. The decrease of Optic Atrophy 1 (OPA1) and the increase of Dynamin-related protein 1 (Drp1) could lead to the dysfunction of mitochondria in PD. Meanwhile, the neuroprotection of parkin need OPA1 exist.Taken together, there is a close relationship between parkin and PD. Parkin silence could lead to typical pathological characteristics of PD in cells. Parkin can maintain mitochondrial stability to reduce cells apotosis. Meanwhile, the neuroprotection of parkin need OPA1 exist.