Search for the proteins linked to Alzheimer's disease-specific neuronal death and application for the therapeutics.
寻找与阿尔茨海默病特异性神经元死亡相关的蛋白质及其治疗应用。
基本信息
- 批准号:13670651
- 负责人:
- 金额:$ 2.3万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2001
- 资助国家:日本
- 起止时间:2001 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Intracellular amyloid-β (Aβ) 42, the major constituent of the senile plaques in the Alzheimer's disease (AD) brain, may be even more important in the AD-related neuronal death than extracellular Aβ42. Previously, we have reported that intracellular Aβ42 contributes to the p53-dependent neuronal death. To further understand the mechanism of AD-specific neuronal death, we are searching for the novel proteins related to that mechanism. Recently, we have established a fine differential display system of intracellular proteins using 2-demensional electrophoresis (2DE). Presenilin (PS) 1 and 2 are the major causes of early-onset familial AD, and the mutations in PS1/2 are deeply associated with the AD-specific neuronal death. Also, extrinsic stress such as oxidative stress may trigger the neuronal death in AD. Thus, we compared the protein profiles in the mutant PS1/2- and wild-type PS1/2-transfected SH-SY5Y cells in the normal condition or stressed condition, e.g. deprivation of serum in the medium. In this case, appearing (increasing) or disappearing (decreasing) protein spots in the stressed mutant PS1/2-transfected cells may be importantly associated with the process of PS1/2 mutation-related cell death. We have selected some candidate spots out of total 500-2000 spots, and attempting to identify these proteins using mass-spectrometry system. Those proteins would be associated with cell cycle, ER stress, ubiquitin-proteasome, signal transduction, or unknown other systems. Thus, 2DE-differential display is a unique tool for searching for disease-related proteins, and may contribute to development of the cure of AD-related neurodegeneration.
细胞内β淀粉样蛋白(Aβ)42是阿尔茨海默病(AD)脑内老年斑的主要成分,在AD相关神经元死亡中可能比细胞外Aβ42更重要。此前,我们曾报道细胞内Aβ42导致p53依赖性神经元死亡。为了进一步了解AD特异性神经元死亡的机制,我们正在寻找与该机制相关的新蛋白。近年来,我们建立了一个精细的细胞内蛋白质双向电泳差异显示系统。早老素(PS)1和2是早发性家族性AD的主要致病基因,PS 1/2基因突变与AD特异性神经元死亡密切相关。此外,外源性应激如氧化应激可触发AD中的神经元死亡。因此,我们比较了在正常条件或应激条件下,例如在培养基中去除血清,突变型PS1/2和野生型PS1/2转染的SH-SY 5 Y细胞中的蛋白质谱。在这种情况下,出现(增加)或消失(减少)的蛋白质点在应激突变PS1/2转染细胞可能是重要的与PS1/2突变相关的细胞死亡的过程。我们从500-2000个蛋白质点中筛选出一些候选蛋白质点,并尝试用质谱系统鉴定这些蛋白质。这些蛋白质可能与细胞周期、内质网应激、泛素-蛋白酶体、信号转导或其他未知系统相关。因此,2DE差异显示是一个独特的工具,寻找疾病相关的蛋白质,并可能有助于开发治疗AD相关的神经退行性变。
项目成果
期刊论文数量(27)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Tanaka, K. et al.: "Suppression of transthyretin expression by ribozymes: implication for a gene therapy for familial amyloid polyneuropathy."Journal of the Neurological Sciences. 183. 79-84 (2001)
Tanaka, K. 等人:“核酶对转甲状腺素蛋白表达的抑制:对家族性淀粉样多发性神经病基因治疗的影响。”神经科学杂志。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Miyoshi, Y. et al.: "A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to Chromosome 8p22.1-24.1"Neurology. 57. 96-100 (2001)
Miyoshi, Y. 等人:“一种与染色体 8p22.1-24.1 相关的新型常染色体显性脊髓小脑共济失调 (SCA16)”神经病学。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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- 通讯作者:
Matsumoto, S. et al.: "Periodic alternating nystagmus in a patient with multiple sclerosis."Neurology. 56. 276-277 (2001)
Matsumoto, S. 等人:“多发性硬化症患者的周期性交替眼球震颤。”神经病学。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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- 通讯作者:
Osoegawa, M. et al.: "Localized myelitis caused by visceral larva migrans due to Ascaris suum masquerading as an isolated spinal cord tumour."Journal of Neurology, Neurosurgery and Psychiatry. 70. 265-266 (2001)
Osoekawa, M. 等人:“由于猪蛔虫伪装成孤立的脊髓肿瘤,导致内脏幼虫移行症引起的局限性脊髓炎。”神经病学、神经外科和精神病学杂志。
- DOI:
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- 影响因子:0
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Miura, S. et al.: "A patient with delayed posthypoxic demyelination : a case report of hyperbalic oxygen treatment"Clinical Neurology and Neurosurgery. 104. 311-314 (2002)
Miura, S. 等人:“一名迟发性缺氧后脱髓鞘患者:高压氧治疗的病例报告”《临床神经病学和神经外科》。
- DOI:
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- 影响因子:0
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OHYAGI Yasumasa其他文献
OHYAGI Yasumasa的其他文献
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{{ truncateString('OHYAGI Yasumasa', 18)}}的其他基金
Development of apomorphine therapy for Alzheimer disease
阿朴吗啡治疗阿尔茨海默病的进展
- 批准号:
22590936 - 财政年份:2010
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of methods to inhibit apoptosis induced by intracellular amyloid β-protein in Alzheimer's disease
开发抑制阿尔茨海默病细胞内β淀粉样蛋白诱导的细胞凋亡的方法
- 批准号:
18590948 - 财政年份:2006
- 资助金额:
$ 2.3万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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人体活体标本对淀粉样β-蛋白寡聚化的影响分析
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19590976 - 财政年份:2007
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Development of methods to inhibit apoptosis induced by intracellular amyloid β-protein in Alzheimer's disease
开发抑制阿尔茨海默病细胞内β淀粉样蛋白诱导的细胞凋亡的方法
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Analyses on oxidative stress and amyloid β protein in brains of mice with modified apolipoprotein E gene
载脂蛋白E基因修饰小鼠脑内氧化应激及β淀粉样蛋白分析
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18500277 - 财政年份:2006
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Herp 在 β 淀粉样蛋白生成和 ER 应激中的作用分析
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Free -radical generation by amyloid p protein and the protective effect by laminin against amyloid β-protein induced toxicity
淀粉样p蛋白产生自由基以及层粘连蛋白对淀粉样β蛋白诱导的毒性的保护作用
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Analysis of the relationship between Amyloid β protein and cholesterol in Alzheimer's disease.
阿尔茨海默病β淀粉样蛋白与胆固醇的关系分析。
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15590891 - 财政年份:2003
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Molecular mechanisms of γ-cleavage for the generation of amyloid β-protein
γ-裂解产生β-淀粉样蛋白的分子机制
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