RNAi-mediated Gene Silencing Therapy for Motor Neuron Disease.
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Accession number;06A0292923
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| Title;RNAi-mediated Gene Silencing Therapy for Motor Neuron Disease. |
| Author;
ISHIGAKI SHINSUKE
(Nagoya Univ., Graduate School of Medicine, JPN)
SOBUE GEN
(Nagoya Univ., Graduate School of Medicine, JPN)
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Journal Title;Neurological Therapeutics
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Journal Code:X0110A
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ISSN:0916-8443
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VOL.23;NO.1;PAGE.25-29(2006)
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| Figure&Table&Reference;TBL.1, REF.14 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Amyotrophic lateral sclerosis (ALS), one of the most common neurodegenerative disorders, is characterized by selective motor neuron degeneration in the spinal cord, brainstem, and cortex. About 10% of ALS are familial; 10%-20% of these cases are caused by Cu/Zn superoxide dismutase (SOD1) gene mutations. Although, the precise mechanism causing motor neuron death in ALS is still unknown, accumulating evidences has suggested that mutant SOD1 proteins caused motorneuronal death in a toxic-gain-of-function manner. In this point of view, the strategy to reduce the expression of mutant SOD1 should be promising for the treatment of mutant SOD1-associated ALS. RNA interference (RNAi) has recently emerged as a powerful gene-silencing tool. There were several reports that attempted to silent mutant SOD1 in cell- or mouse-model of ALS. Earlier and greater knockdown of mutant SOD1 expression contributed to halt or slow the disease onset and progression of mutant SOD1 transgenic mice models. Wild type SOD1 might be eventually knocked down with RNAi-mediated knock down of mutant SOD1. Since SOD1 knockout mice did not show any motor neuron dysfunction, this side effect can be overwhelmed by the advantage of the RNAi therapy. Thus, the RNAi therapy targetting mutant SOD1 can be a useful tool for the treatment of mutant SOD1-assocciated ALS. (author abst.) |
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