New polyglutamine diseases : from the neuropathologies to the identification of genes responsible for the diseases

新的多聚谷氨酰胺疾病：从神经病理学到识别导致疾病的基因

• 批准号: 16390104
• 负责人: TAKAHASHI Hitoshi
• 金额: $ 3.84万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390104/
• 关键词: Spinocerebellar ataxia; 1C2; polyglutamine diseases; Western blotting; Two-dimensional electrophoresis; amino acid sequence; 小脳変性症; ウェスタンブロッティング

We have studied three patients with pathologically different hereditary spinocerebellar ataxia characterized by 1C2-immunopositive intranuclear inclusions in the affected CNS neurons, namely, polyglutamine diseases. We have also tried to identify the gene responsible for each hereditary disease.(1)We have described a homozygous case of spinocerebellar ataxia type 17 with 48 glutamines. The age of the patient at disease onset was lower than those of heterozygotes with the same CAG-repeat sizes, but the clinical manifestations were rapidly progressive dementia and chorea. Neuronal loss was relatively restricted and most prominent in the Purkinje cell layer and striatum ; however, intranuclear neuronal polyglutamine accumulation was widespread, with a high frequency in the cerebral cortex and striatum.(2)In one of the other two cases, immunoblotting analyses with a monoclonal antibody specific for expanded polyglutamine stretches (1C2) revealed the presence of immunopositive proteins. Furthermore, we identified multiple spots, one of which might be the disease-related protein, using two-dimensional electrophoresis and two-dimensional immunoblotting methods. Further studies are needed to identify the gene responsible for the disease.(3)In the final case, we are trying the same methods to identify the disease-related protein and the causative gene abnormality.

我们研究了3例病理学不同的遗传性脊髓小脑共济失调患者，其特征为受影响的中枢神经系统神经元中的1C 2-免疫阳性核内包涵体，即多聚谷氨酰胺疾病。我们还试图找出导致每种遗传性疾病的基因。(1)We已经描述了一个纯合子的情况下，脊髓小脑共济失调17型与48谷氨酰胺。患者的发病年龄低于具有相同CAG重复序列大小的杂合子，但临床表现为快速进行性痴呆和舞蹈病。神经元损失相对有限，最突出的浦肯野细胞层和纹状体，然而，核内神经元聚谷氨酰胺的积累是广泛的，在大脑皮层和纹状体的频率很高。(2)In在另外两种情况中，用对扩增的多聚谷氨酰胺片段（1C 2）特异的单克隆抗体进行免疫印迹分析，发现存在免疫阳性蛋白。此外，我们确定了多个点，其中之一可能是疾病相关的蛋白质，使用二维电泳和二维免疫印迹方法。需要进一步的研究来确定导致这种疾病的基因。(3)In最后一种情况，我们正在尝试相同的方法来鉴定疾病相关蛋白和致病基因异常。

项目成果

ポリグルタミン病における神経細胞変性機構.

多聚谷氨酰胺疾病中神经元变性的机制。

• 发表时间: 2005
• 期刊: 実験医学 23
• 作者: Sun Y;Witte DP;Zamzow M;Ran H;Quinn B;Matsuda J;Grabowski GA.;山田光則
• 通讯作者: 山田光則

β-synuckein gene alteration in dementia with Lewy bodies.

路易体痴呆症中的β-突触蛋白基因改变。

• 发表时间: 2004
• 期刊: Neurology 63
• 作者: Toyama-Sorimachi;N.;Y.toyoshima;Toyoshima Y;Koko Katagiri;Toyoshima Y;Kenji Kawada;Hiroshi Fukaya;Ohtake H
• 通讯作者: Ohtake H

Familial amyotrophic lateral sclerosis with bulbar onset and a novel Asp101Tyr Cu/Zn superoxide dismutase gene mutation

• DOI: 10.1007/s00401-004-0893-4
• 发表时间: 2004-10-01
• 期刊: ACTA NEUROPATHOLOGICA
• 影响因子: 12.7
• 作者: Tan, CF;Piao, YS;Takahashi, H
• 通讯作者: Takahashi, H

Spinocerebellar ataxia type 17 repeat in patients with Huntington's disease-like and ataxia, reply

亨廷顿病样和共济失调患者中脊髓小脑共济失调 17 型重复，回复

• 发表时间: 2004
• 期刊: Annals of Neurology 56(1)
• 作者: Yasuko Toyoshima

Polyglutamine disease : recent advances in the neuropathology of DRPLA

多聚谷氨酰胺病：DRPLA神经病理学的最新进展

• 发表时间: 2006
• 期刊: Neuropathology 26(In press)
• 作者: Hamada;J.;浜田淳一;Sayuri Yamazaki;Kunie Saito;Kunie Saito;Sayuri Yamazaki;Kunie Saito;Sayuri Yamazaki;Ralph M.Steinman;Kayo Inaba;Koji Nagaoka;Clare L.Bennett;Yoshiki Omatsu;Takeshi Nakahara;Noriko Toyama-Sorimachi;Takeshi Nakahara;Noriko Toyama-Sorimachi;Omatsu Yoshiki;Clare L.Bennett;Kayo Inaba;Koji Nagaoka;M.Yamada
• 通讯作者: M.Yamada