| Budget Amount *help |
¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2012: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2011: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
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| Research Abstract |
Amyotrophic lateral sclerosis (ALS) is a heterogeneous group of fatal neurodegenerative diseases characterized by a selective loss of motor neurons in the brain and spinal cord. Although multiple toxicity pathways including oxidative stress, neural inflammation, protein misfolding and accumulation, and dysfunctional intracellular trafficking, are implicated in the pathogenesis of ALS, molecular basis of the interplay between such multiple factors are largely unknown. To address this issue, we investigate a role of GFAP, Nrf2, ALS2, and p62/SQSTM1 , and their interrelationship in the onset and progression of ALS using mutant SOD1-expressing ALS mouse models. The results indicate that loss of either ALS2 or p62/SQSTM1 exacerbates motor dysfunction in ALS mice. Importantly, a simultaneous inactivation of ALS2 and p62/SQSTM1 in ALS mice further accelerates the disease phenotypes. Thus, dysfunction in the autophagy-endolysosomal system might play a crucial role in motor neuron degeneration.
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