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- W85788059 abstract "Parkinson's disease (PD) is a common neurodegenerative movement disorder. Mutation of LRRK2 is pathogenic in PD. So far, more than 20 mutations of LRRK2 have been reported in Parkinson patients of different races. Some of the mutations were shown to be able to increase. We aim to elucidate the importance of LRRK2 in the pathogenesis of PD by studying the effects of this protein on vulnerability of neuronal cell death under oxidative stress. Materials and Methods We have developed stable HEK293 cells overexpressing wild-type and mutated (R1441G, G2019S) LRRK2. The effects of LRRK2 over-expression on various mitochondrial parameters were determined, e.g. cell viability, mitochondrial complexes (I–IV) activity and membrane potential, ATP/ADP ratio, and mitochondrial fragmentation after challenged with H2O2 to induce oxidative stress. We generated R1441G LRRK2 knockin (KI) mice. We are characterizing the LRRK2 R1441G KI mice and wildtype mice by immunohistochemistry of tyrosine hydroxylase (TH) to identify TH+ neurons after challenged with MPTP injection (IP) for 2 weeks to induce nigrostriatal degeneration. Results Our preliminary data showed that the intracellular expression pattern of mutant LRRK2 (G2019S) in HEK293 was different from the wild-type under oxidative stress by H2O2. Mutant LRRK2 was translocated towards mitochondria after treatment with H2O2. LDH release and ATP/ADP ratio proved more serious trend of apoptosis in mutant LRRK2 cell lines. Mitochondrial complexes I activity and mitochondrial fragmentation level were also changed between wild type and single mutation proteins (R1441G and G2019S) in HEK293. The results of this study have important implication on understanding the mitochondrial dysfunction in the pathogenesis of PD." @default.
- W85788059 created "2016-06-24" @default.
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- W85788059 date "2010-04-01" @default.
- W85788059 modified "2023-10-01" @default.
- W85788059 title "Understanding molecular mechanisms in mitochondria underlying LRRK2‐related Parkinson's disease" @default.
- W85788059 doi "https://doi.org/10.1096/fasebj.24.1_supplement.891.3" @default.
- W85788059 hasPublicationYear "2010" @default.
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