| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
We previously demonstrated that CRAG facilitated the degradation of expanded polyglutamine protein via the nuclear ubiquitin-proteasome pathway and suggested that targeted delivery of CRAG may be useful as a gene therapy for neurodegenerative diseases such as polyglutamine diseases. However, the physiological relevance of CRAG in vivo is unknown. Here, we analyzed CRAG KO mice. Both whole-body and neuron-specific CRAG KO mice spontaneously developed severe neurodegenerative phenotypes cell death and lethality, within 1 month of birth. Kainic acid–induced c-fos expression was intensively suppressed in the hippocampus in these KO mice. Furthermore, CRAG interacted with ELK1, a coactivator of SRF, leading to ELK1-dependent SRF-c-fos induction. We conclude that CRAG plays a critical role in neuronal development and survival, at least in part through ELK1-dependent SRF-c-fos activation, and therefore suggesting the usefulness of CRAG gene therapy for neurodegenerative diseases.
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