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质膜1型电压依赖性阴离子通道（VDAC）与β淀粉样蛋白（Aβ）肽通过GxxxG模体发生的凋亡相互作用引发阿尔茨海默病——一种凋亡的基本模型？

Apoptogenic interactions of plasmalemmal type-1 VDAC and Aβ peptides via GxxxG motifs induce Alzheimer's disease - a basic model of apoptosis?

作者信息

Thinnes Friedrich P

出版信息

Wien Med Wochenschr. 2011 May;161(9-10):274-6. doi: 10.1007/s10354-011-0887-5. Epub 2011 Apr 4.

DOI:10.1007/s10354-011-0887-5
PMID:21442216
Abstract

Human type-1 porin/VDAC (voltage-dependent anion channel) carries a GxxxG motif in its N-terminal part, traversing the β-barrel, while the Alzheimer's disease (AD) relevant amyloid peptides Aβ1-42 and Aβ1-40 show a series of corresponding motifs close to their C-terminus. GxxxG motifs are established as aggregation/membrane perturbation motifs. These peptide primary structure data support a proposal I recently made on the basis of a synopsis of recent literature. Accordingly, amyloid Aβ, cut from APP by beta-secretase BACE1 and gamma-secretase, has been insinuated to induce Alzheimer's disease via apoptosis by opening type-1 porin/VDAC in cell membranes of hypometabolic neuronal cells. Considering the ubiquitous expression modus of APP, beta- and gamma-secretases and type-1 VDAC/eukaryotic porin a basic model of apoptosis might be given.

摘要

人类1型孔蛋白/电压依赖性阴离子通道（VDAC）在其N端部分携带一个GxxxG基序，该基序贯穿β桶结构，而与阿尔茨海默病（AD）相关的淀粉样肽Aβ1-42和Aβ1-40在其C端附近显示出一系列相应的基序。GxxxG基序已被确定为聚集/膜扰动基序。这些肽的一级结构数据支持了我最近根据近期文献综述提出的一个提议。因此，由β-分泌酶BACE1和γ-分泌酶从淀粉样前体蛋白（APP）切割而来的淀粉样Aβ，被认为通过打开低代谢神经元细胞膜中的1型孔蛋白/VDAC，经由凋亡诱导阿尔茨海默病。考虑到APP、β-和γ-分泌酶以及1型VDAC/真核孔蛋白的普遍表达模式，可能会给出一个凋亡的基本模型。

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Evidence for functional interaction of plasma membrane electron transport, voltage-dependent anion channel and volume-regulated anion channel in frog aorta.血浆膜电子传递、电压依赖性阴离子通道和体积调节性阴离子通道在蛙主动脉中的功能相互作用的证据。
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Adverse Effects of Metformin From Diabetes to COVID-19, Cancer, Neurodegenerative Diseases, and Aging: Is VDAC1 a Common Target?二甲双胍的不良反应：从糖尿病到新冠病毒病、癌症、神经退行性疾病及衰老——电压依赖性阴离子通道1是共同靶点吗？
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VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases.电压依赖性阴离子通道 1 在细胞代谢、细胞凋亡及疾病中的作用
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