2012 Fiscal Year Final Research Report
Elucidation of cell death mechanism by dominant negative ofmutant LRRK2, the causative molecule of Parkinson's disease
| Project/Area Number |
23791000
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Kitasato University |
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Principal Investigator |
OHTA Etsuro 北里大学, 医療衛生学部, 講師 (60508042)
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| Project Period (FY) |
2011 – 2012
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| Keywords | パーキンソン病 / LRRK2 / 細胞死 / ヘテロ二量体 / Akt1 |
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| Research Abstract |
Mutant Leucine-rich repeat kinase 2 (LRRK2) is the molecule responsible for autosomal dominant Parkinson’s disease (PD). In the present study, we found that the lifetime of WT LRRK2 protein was shortened by formation of a heterodimer with I2020T LRRK2. We also demonstrated that the kinase activity of WT LRRK2 for phosphorylation of Akt1 was diminished by the presence of I2020T LRRK2. Furthermore, the protective effect of WT LRRK2 against H2O2-induced apoptosis was impaired by co-transfection with I2020T LRRK2. These results provide a new insight into the etiology of PD caused by the LRRK2 mutation, i.e., a dominant-negative effect resulting from heterodimer formation.
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