| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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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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