Shedding activity and physiological role of a newly-found ADAM family metalloprotease family

新发现的 ADAM 家族金属蛋白酶家族的脱落活性和生理作用

• 批准号: 13480202
• 负责人: ISHIURA Shoichi
• 金额: $ 4.8万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13480202/
• 关键词: Alzheimer's disease; amyloid; protease; secretase; shedding; ADAM; therapy; aging; 脳神経疾患; 遺伝子; 蛋白質; 神経科学; αセクレターゼ; dsRNA; 脳

The neurodegeneration in Alzheimer's disease may be caused by deposition of amyloid β peptide (Aβ) in plaques in brain tissue. Mechanisms of Aβ production in the brain have been the subject of considerable interest. Several factors regulate processing of amyloid precursor protein (APP), which is cleaved by three types of membrane-bound proteases designated α-, β-, and γ-secretases. Although we are only beginning to understand their function the discovery of nonamyloidogenic α-secretase has already provided some answers to longstanding questions of Alzheimer drug development. Here we summarize recent advances in the identification of APP α-secretases. Pharmacological up-regulation of α-secretases should provide rational drug design for Alzheimer's disease.

阿尔茨海默病（Alzheimer 'sdisease，AD）的神经退行性变可能是由于脑组织中淀粉样β肽（amyloid β peptide，Aβ）在斑块中沉积所致。脑中Aβ产生的机制一直是相当感兴趣的主题。淀粉样前体蛋白（APP）的加工过程受多种因素的调节，APP由三种类型的膜结合蛋白酶（称为α-、β-和γ-分泌酶）切割。虽然我们才刚刚开始了解它们的功能，但非淀粉样α分泌酶的发现已经为阿尔茨海默病药物开发的长期问题提供了一些答案。本文就APP α分泌酶的研究进展作一综述。α-分泌酶的药理学上调应该为阿尔茨海默病提供合理的药物设计。

项目成果

Hattori, C. et al.: "BACEI interacts with nicastrin"Biochem. Biophys. Res. Commun.. 293. 1228-1232 (2002)

Hattori, C. 等人：“BACEI 与烟碱相互作用”Biochem。

IQ遺伝子

智商基因

• 发表时间: 2002
• 作者: 石浦章一

Suo, S., et al.: "Identification of a dopamine receptor from C.elegans"Neurosci Lett. 319. 13-16 (2002)

Suo，S.，等人：“线虫多巴胺受体的鉴定”Neurosci Lett。

A secreted form of ADAM9 has an α-secretase activity for APP.

ADAM9 的分泌形式具有 APP 的 α-分泌酶活性。

• 发表时间: 2002
• 期刊: Biochem.Biophys.Res.Commun. 293
• 作者: Hotoda;N.;Koike;H.;Sasagawa;N.;Ishiura;S.
• 通讯作者: S.

Hotoda, N., et al.: "Amyloid precursor protein is secreted by membrane-anchored metalloprotease ADAM9"Cell Surface Aminopeptidase. 401-406 (2001)

Hotoda, N. 等人：“淀粉样前体蛋白由膜锚定金属蛋白酶 ADAM9”细胞表面氨基肽酶分泌。