Identification of a new causative gene of amyotrophic lateral sclerosis; optineurin
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- Maruyama Hirofumi
- Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University
Bibliographic Information
- Other Title
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- 筋萎縮性側索硬化症の新規原因遺伝子optineurinの同定
- 日本神経学会賞受賞 筋萎縮性側索硬化症の新規原因遺伝子optineurinの同定
- ニホン シンケイ ガッカイショウ ジュショウ キン イシュクセイ ソクサク コウカショウ ノ シンキ ゲンイン イデンシ optineurin ノ ドウ テイ
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Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating disorder characterized by degeneration of motor neurons of the primary motor cortex, brainstem and spinal cord. ALS patients die within 3 to 5 years without respiratory support. Detecting the causing gene is necessary to elucidate ALS.<br> We identified mutations of optineurin (OPTN) in ALS. We found three types of mutation of OPTN: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Cell transfection experiments showed that the nonsense and missense mutations of OPTN abolished the inhibition of activation of nuclear factor kappa B. The missense mutation revealed a cytoplasmic distribution different from that of the wild type.<br> A case with the E478G mutation showed OPTN-immunoreactive cytoplasmic retention, and Golgi fragmentation was identified in 70% of the anterior horn cells. TDP-43- or SOD1-positive inclusions of sporadic and SOD1 cases of ALS were also immunolabelled with anti-OPTN antibodies. Furthermore, optineurin is co-localized with fused in sarcoma (FUS) in basophilic inclusions of ALS with FUS mutation and in basophilic inclusion body disease.<br> Our findings suggest that OPTN is involved in the great part of pathogenesis of ALS.<br>
Journal
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- Rinsho Shinkeigaku
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Rinsho Shinkeigaku 52 (1), 1-5, 2012
Societas Neurologica Japonica
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Details 詳細情報について
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- CRID
- 1390001205037493248
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- NII Article ID
- 40019173877
- 130004505018
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- NII Book ID
- AN00253207
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- ISSN
- 18820654
- 0009918X
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- NDL BIB ID
- 023459981
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed