STUDIES ON MOLECULAR AND CLINICAL PATHOMECHANISM OF SPINOCEREBELLAR DEGENERATION

脊髓小脑变性的分子及临床发病机制研究

• 批准号: 12307013
• 负责人: MIZUSAWA Hidehiro
• 金额: $ 27.7万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12307013/
• 关键词: SPINOCEREBELLAR DEGENERATION; CAG REPEAT; SCA6; CA CHANNEL; PURKINJE CELL; ANIMAL MODEL; CACNA1A; αTTP; CAGピート; ノックインマウス; CACN1A; 脊髄小脳変形症; ES細胞; CACNAIA

In the research on pathogenesis of spinocerebellar ataxia type 6 (SCA6), we found Purkinje cell specific inclusions and SCA6 gene resulted in Ca channel abnormality in cultured cells. A new gene locus for pure cerebellar ataxia was disclosed and the candidate area was narrowed. Regarding glial cytoplasmic inclusions in multiple system atrophy, we identified the 7 KD core fragment of α-synuclein molecule.

在脊髓小脑性共济失调6型（spinocerebellar ataxia type 6, SCA6）发病机制的研究中，我们发现浦肯野细胞特异性包涵体和SCA6基因导致培养细胞Ca通道异常。发现了一个新的单纯小脑性共济失调基因位点，缩小了候选区域。对于多系统萎缩的胶质细胞质内含物，我们鉴定了α-突触核蛋白分子的7 KD核心片段。

项目成果

Toru S, Murakoshi T, Ishikawa K, Saegusa H, Fujigasaki H, Uchihara T, Nagayama S, Osanai M, Mizusawa H, Tanabe T: "Spinocerebellar ataxia type 6 mutation alters P-type calcium channel function"J Biol Chem. 275. 10893-10898 (2000)

Toru S、Murakoshi T、Ishikawa K、Saegusa H、Fujigasaki H、Uchihara T、Nagayama S、Osanai M、Mizusawa H、Tanabe T：“脊髓小脑共济失调 6 型突变改变 P 型钙通道功能”J Biol Chem。

Yokota T, Uchihara T, Kumagai J, Shiojiri T, Pang JJ, Arita M, Arai H, Hayashi M, Kiyosawa M, Okeda R, Mizusawa H: "Postmortem study of ataxia with retinitis pigmentosa by mutation of the α-tocopherol transfer protein"J Neurol Neurosurg Psychiatry. 68. 52

Yokota T、Uchihara T、Kumagai J、Shiojiri T、Pang JJ、Arita M、Arai H、Hayashi M、Kiyosawa M、Okeda R、Mizusawa H：“α-生育酚转移蛋白突变导致共济失调伴色素性视网膜炎的尸检研究“神经外科精神病学杂志。68. 52

Fujigasaki H, Uchihara T, Koyano S, Iwabuchi K, Yagishita S, Makifuchi T, Nakamura A, Ishida K, Toru S, Hirai S, Ishikawa K, Tanabe T, Mizusawa H: "Ataxin-3 is translocated into the nucleus for the formation of intranuclear inclusions in normal and Machad

Fujigasaki H、Uchihara T、Koyano S、Iwabuchi K、Yagishita S、Makifuchi T、Nakamura A、Ishida K、Toru S、Hirai S、Ishikawa K、Tanabe T、Mizusawa H：“Ataxin-3 转位到细胞核中，用于

Takashima M, Ishikawa K, Nagaoka U, Shoji S, Mizusawa H: "A linkage disequilibrium at the candidate gene locus, for 16q-linked autosomal dominant cerebellar ataxia type III in Japan"J Hum Genet. 46. 167-171 (2001)

Takashima M、Ishikawa K、Nagaoka U、Shoji S、Mizusawa H：“日本 16q 连锁常染色体显性小脑共济失调 III 型候选基因位点的连锁不平衡”J Hum Genet。

Miura Y, Misawa N, Maeda N, Inagaki Y, Tanaka Y, Ito M, Kayagaki N, Yamamoto N, Yagita H, Mizusawa H, Koyanagi Y: "Critical contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to apoptosis of human CD4+ T cells in HIV-1-infecte

Miura Y、Misawa N、Maeda N、Inagaki Y、Tanaka Y、Ito M、Kayagaki N、Yamamoto N、Yagita H、Mizusawa H、Koyanagi Y：“肿瘤坏死因子相关凋亡诱导配体 (TRAIL) 对细胞凋亡的关键贡献