| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Outline of Final Research Achievements |
(1) In amyotrophic lateral sclerosis (ALS), TDP-43 trafficking between the nucleus and the cytoplasm is disturbed, resulting in an accumulation of TDP-43 in the cytoplasm in the form of insoluble aggregates. (2) Autophagy is significantly activated in the cytoplasm of motor neurons in sporadic ALS and may be involved in the pathomechanism of the neurodegeneration of motor neurons. (3) ADAR2-reduction is associated with progressive deterioration of nuclear architecture, resulting in vacuolated nuclei due to a Ca2+-permeable AMPA receptor-mediated mechanism. (4) Significantly increased autophagy flux in the degenerating motor neurons of ADAR2-knockout mice likely resulted from Ca2+ overload. (5) The temporary and reversible breakdown of the blood-spinal cord barrier at the early symptomatic stage could be a direct pathogenic consequence of the loss of TDP-43 protein in TDP conditional knockout mice.
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