| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Outline of Final Research Achievements |
Parkinson disease is genetically caused by mutations in LRRK2. We found that neurons expressing mutant LRRK2 decreased the mitochondrial energetics and mitochondrial calcium signaling. Mitochondrial calcium is introduced through the contact site between endoplasm (ER) and mitochondria and regulates mitochondrial energetics. LRRK2 interacted with mitochondrial ubiquitin ligases, which regulated components in the ER-mitochondrial interaction Neuron expressing mutant LRRK2 inhibited the activities of these ligases, and then accumulated components disturbed the ER-mitochondrial interaction and ER stress response, resulting in the increased ER stress and apoptotic death of neurons. The treatment with activators for PERK, one of the ER stress inducers, rescued these defects in neuron expressing mutant LRRK2. Thus, our result provides new insight for the treatment for Parkinson disease.
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