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Mutant superoxide dismutase 1 causes motor neuron degeneration independent of cyclin-dependent kinase 5 activation by p35 or p25

https://asahikawa-med.repo.nii.ac.jp/records/721
https://asahikawa-med.repo.nii.ac.jp/records/721
a3071e29-5db4-4001-b0a2-5acd1cbed147
名前 / ファイル ライセンス アクション
901.pdf 901.pdf (747.0 kB)
Item type 学術雑誌論文 / Journal Article_02(1)
公開日 2008-03-28
タイトル
タイトル Mutant superoxide dismutase 1 causes motor neuron degeneration independent of cyclin-dependent kinase 5 activation by p35 or p25
言語 en
言語
言語 eng
資源タイプ
資源タイプ journal article
著者 高橋, 悟

× 高橋, 悟

高橋, 悟

ja-Kana タカハシ, サトル

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Kulkarni, AB

× Kulkarni, AB

Kulkarni, AB

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著者 ローマ字
Takahashi, Satoru
書誌情報 Journal of Neurochemistry

巻 88, 号 5, p. 1295-1304, 発行日 2004-01-01
ISSN
収録物識別子タイプ ISSN
収録物識別子 0022-3042
DOI
識別子タイプ DOI
関連識別子 10.1046/j.1471-4159.2003.02256.x
リンクURL
内容記述タイプ Other
内容記述 http://www.blackwell-synergy.com/doi/abs/10.1046/j.1471-4159.2003.02256.x | http://www.blackwell-synergy.com/doi/abs/10.1046/j.1471-4159.2003.02256.x
抄録
内容記述タイプ Abstract
内容記述 Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective loss of motor neurons in the brain and spinal cord. Neurotoxicity mediated by glutamate is thought to play a role in the neuronal death through intracellular calcium-dependent signaling cascades. Cyclin-dependent kinase 5 (Cdk5) has been proposed as one of the calcium-dependent mediators that may cause neuronal death observed in this disease. Cdk5 is activated in neurons by the association with its activators, p35 or p39. The calcium-activated protease calpain cleaves p35 to its truncated product, p25, which eventually causes the cellular mislocalization and prolonged activation of Cdk5. This deregulated Cdk5 induces cytoskeletal disruption and apoptosis. To examine whether inhibition of the calpain-mediated conversion of p35 to p25 can delay the disease progression of ALS, we generated double transgenic mice in which ALS-linked mutant copper/zinc superoxide dismutase 1 (SOD1G93A) was expressed in a p35-null background. The absence of p35 neither affected the onset and progression of motor neuron disease in the mutant SOD1 mice nor ameliorated the pathological lesions in these mice. Our results provide direct evidence that the pathogenesis of motor neuron disease in the mutant SOD1 mice is independent of the Cdk5 activation by p35 or p25.
注記
内容記述タイプ Other
注記 Blackwell Publishing, Satoru, Takahashi ; Ashok B. Kulkarni, Journal of Neurochemistry, 88(5), 2004, 1295-1304
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資源タイプ text
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高橋, 悟, Kulkarni, AB, n.d., Mutant superoxide dismutase 1 causes motor neuron degeneration independent of cyclin-dependent kinase 5 activation by p35 or p25: 1295–1304 p.

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