BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and β-amyloid production in Alzheimer's disease.
BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and β-amyloid production in Alzheimer's disease.
复制标题
DOI：
10.1186/1750-1326-7-52
复制
发表时间：
2012-10-05
影响因子：
15.1
通讯作者：
Checler F
中科院分区：
文献类型：
--
作者：
Chami L;Checler F
阿尔茨海默病（AD）是一种复杂的与年龄相关的疾病，其病因尚未明确界定。在各种组织学特征中，受AD影响的大脑呈现出多种细胞功能障碍，反映出氧化应激增强、炎症过程以及钙稳态失调。这些变化中的大多数都直接或间接与β-淀粉样肽（Aβ）有关，其产生、分子性质和生物物理特性可能影响退行性过程。特别值得注意的是，在一个反向控制过程中，上述细胞功能障碍会改变Aβ肽的水平。β-分泌酶βAPP切割酶1（BACE1）是这种相互作用的关键分子因素。这种酶负责产生“全长”Aβ肽N端的初次切割，并且还会受到多种细胞应激的转录诱导。这篇综述总结了将脑损伤与AD样疾病相关联的数据，并证明了BACE1在导致Aβ产生的恶性循环交叉点上的关键作用。
Alzheimer’s disease (AD) is a complex age-related pathology, the etiology of which has not been firmly delineated. Among various histological stigmata, AD-affected brains display several cellular dysfunctions reflecting enhanced oxidative stress, inflammation process and calcium homeostasis disturbance. Most of these alterations are directly or indirectly linked to amyloid β-peptides (Aβ), the production, molecular nature and biophysical properties of which likely conditions the degenerative process. It is particularly noticeable that, in a reverse control process, the above-described cellular dysfunctions alter Aβ peptides levels. β-secretase βAPP-cleaving enzyme 1 (BACE1) is a key molecular contributor of this cross-talk. This enzyme is responsible for the primary cleavage generating the N-terminus of “full length” Aβ peptides and is also transcriptionally induced by several cellular stresses. This review summarizes data linking brain insults to AD-like pathology and documents the key role of BACE1 at the cross-road of a vicious cycle contributing to Aβ production.
登录
查看更多内容
影响因子：
3.6
作者：
Baba, A;Mitsumori, K;Ikegaya, Y
通讯作者：
Ikegaya, Y
影响因子：
56.9
作者：
Cao, XW;Südhof, TC
通讯作者：
Südhof, TC
影响因子：
4.8
作者：
Chami, Linda;Buggia-Prevot, Virginie;Checler, Frederic
通讯作者：
Checler, Frederic
影响因子：
2.1
作者：
Checler, Frederic;Sunyach, Claire;da Costal, Cristine Alves
通讯作者：
da Costal, Cristine Alves
影响因子：
4.5
作者：
Berridge, Michael J.
通讯作者：
Berridge, Michael J.