BRI2 as an anti-Alzheimer gene
BRI2 as an anti-Alzheimer gene
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DOI：
10.1007/s00795-018-0191-1
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发表时间：
2019-03
影响因子：
1.8
通讯作者：
Shuji Matsuda;T. Senda
中科院分区：
文献类型：
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作者：
Shuji Matsuda;T. Senda
关于阿尔茨海默病（AD）的病因有几种理论。考虑到所有与家族性AD相关的基因都是淀粉样蛋白前体（APP）或APP代谢酶，APP代谢异常肯定是AD发病的关键。BRI2是一种II型跨膜蛋白，结合APP并抑制APP蛋白水解的所有α、β和γ途径。将AD模型小鼠与BRI2转基因或BRI2敲除小鼠杂交证实BRI2是抗阿尔茨海默病基因。已知BRI2的突变会导致人类罕见的家族性痴呆。对携带疾病突变的敲入小鼠的分析揭示了小鼠的记忆缺陷，这归因于BRI2保护功能的丧失。需要进一步的研究来破译BRI2的这种抗阿尔茨海默病机制，以开发用于AD的新的治疗应用。本文在介绍AD研究的基本假设后，重点介绍了BRI2作为一个抗阿尔茨海默病基因的研究进展。
There are several theories regarding the etiologies of Alzheimer disease (AD). Considering that all genes responsible for familial AD are amyloid protein precursor (APP) or APP metabolizing enzymes, surely aberrant APP metabolism is crucial to pathogenesis of AD. BRI2, a type II transmembrane protein, binds APP and inhibits all α, β, and γ pathways of APP proteolysis. Crossing AD model mice with BRI2 transgenic or BRI2 knockout mice confirmed that BRI2 is an anti-Alzheimer gene. Mutations of BRI2 are known to cause rare familial dementias in human. Analysis of knock-in mice harboring the disease mutation revealed the memory defect in the mice, attributable to loss of protective function of BRI2. Further studies are needed to decipher this anti-Alzheimer mechanism of BRI2 to develop a novel therapeutic application for AD. In this review, after describing basic assumptions in AD study, we focus on BRI2 as an anti-Alzheimer gene.