| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Amyotrophic lateral sclerosis(ALS) is a progressive fatal neurodegenerative disease that is characterized with specific degeneration of motor neurons. Specific mutations in superoxide dismutase 1(SOD1) are associated with approximately 20% of familial ALS(FALS) cases. SOD1 mutants are considered to cause motoneuronal death by ‘gain of toxic function'. On the other hand, alsin encoded by another FALS-responsible gene, ALS2, is considered to cause ALS by ‘loss of function', because FALS-linked mutations in ALS2 are recessively inherited. Based on the hypothesis that alsin contributes neuroprotection, we examined whether wild-type alsin protect cells from SOD1 mutants-induced toxicity. We found that co-expression of alsin with FALS-linked SOD1 mutant drastically suppressed SOD1 mutants-induced cell death in motoneuronal cell line. Further, the wild-type alsin binds to FALS- linked SOD1 mutants, but not to wild-type SOD1, suggesting that neuroproptection of alsin correlates with complex formation with SOD1 mutants.
We also found that ADNF, a nine-residue polypeptide, suppressed motoneuronal death caused by FALS-linked SOD1 mutants in vitro and improved motor performance of G93A-SOD1 transgenic mice, a model of FALS.
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