| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
The ubiquitin ligase(E3) HRD1 protein levels were significantly decreased in the cerebral cortex of patients with Alzheimer's disease(AD), and that the brains of these patients were under ER stress. Furthermore, HRD1 levels negatively correlated with Aβlevels. The present study revealed that the decrease in HRD1 levels was due to its insolubilization. A reactive oxygen species(ROS)-induced insolubilization of HRD1 and SEL1L may be involved in Aβgeneration in the pathogenesis of AD. Neural stem/progenitor cells(NSCs) reside in the subventricular zone(SVZ) and subgranular zone of the hippocampal dentate gyrus in adult mammals. We found the localization of HRD1 in the NSCs of the adult brain. We found that several 4-phenylbutyric acid 1(4-PBA) derivatives demonstrated anti-aggregation activity as a chemical chaperone activity higher than that of 4-PBA.
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