Chaperone signalling complexes in Alzheimer's disease.
Chaperone signalling complexes in Alzheimer's disease.
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阿尔茨海默氏病中的伴侣信号传导复合物。
DOI：
10.1111/j.1582-4934.2008.00557.x
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发表时间：
2009-04
影响因子：
5.3
通讯作者：
Dickey CA
中科院分区：
文献类型：
--
作者：
Koren J 3rd;Jinwal UK;Lee DC;Jones JR;Shults CL;Johnson AG;Anderson LJ;Dickey CA
分子伴侣和热休克蛋白（HSP）已成为神经退行性疾病病理相关蛋白质的关键调节因子。分子伴侣系统的本质是维持蛋白质质量控制，这意味着大多数新生蛋白质与分子伴侣蛋白质接触。因此，淀粉样前体蛋白（APP）、γ-分泌酶复合物的成员（统称为早老素1 [PS1]）、微管相关蛋白tau（MAPT）以及许多神经炎性组分从产生的那一刻起就与分子伴侣接触。伴侣蛋白通常被组合在一起作为一个机器，将异常或突变蛋白质呈递给蛋白酶体进行降解，但情况并非如此。事实上，伴侣蛋白家族由哺乳动物细胞中的100多种蛋白质组成，其中大多数蛋白质的主要作用是在合成后和压力期间保护客户;只有作为最后手段，它们才促进蛋白质降解。据我们目前所知，真核细胞中的伴侣系统围绕着两个主要的伴侣支架Hsp 70和Hsp 90的ATP酶活性。其他分子伴侣和辅助分子伴侣操纵Hsp 70和Hsp 90的ATP酶活性，促进客户端的折叠或其降解。在阿尔茨海默病（AD）的情况下，最近出现了许多研究，描述了这些分子伴侣对tau蛋白和淀粉样蛋白-β积累的蛋白毒性作用的影响。在这里，我们提出了目前的伴侣生物学的理解，并检查文献调查这些蛋白质的背景下，AD。
Molecular chaperones and heat shock proteins (Hsp) have emerged as critical regulators of proteins associated with neurodegenerative disease pathologies. The very nature of the chaperone system, which is to maintain protein quality control, means that most nascent proteins come in contact with chaperone proteins. Thus, amyloid precursor protein (APP), members of the gamma-secretase complex (presenilin 1 [PS1] collectively), the microtubule-associated protein tau (MAPT) as well as a number of neuroinflammatory components are all in contact with chaperones from the moment of their production. Chaperones are often grouped together as one machine presenting abnormal or mutant proteins to the proteasome for degradation, but this is not at all the case. In fact, the chaperone family consists of more than 100 proteins in mammalian cells, and the primary role for most of these proteins is to protect clients following synthesis and during stress; only as a last resort do they facilitate protein degradation. To the best of our current knowledge, the chaperone system in eukaryotic cells revolves around the ATPase activities of Hsp70 and Hsp90, the two primary chaperone scaffolds. Other chaperones and co-chaperones manipulate the ATPase activities of Hsp70 and Hsp90, facilitating either folding of the client or its degradation. In the case of Alzheimer's disease (AD), a number of studies have recently emerged describing the impact that these chaperones have on the proteotoxic effects of tau and amyloid-β accumulation. Here, we present the current understandings of chaperone biology and examine the literature investigating these proteins in the context of AD.
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影响因子：
9.3
作者：
Colton CA;Mott RT;Sharpe H;Xu Q;Van Nostrand WE;Vitek MP
通讯作者：
Vitek MP
影响因子：
11.2
作者：
Cottrell, BA;Galvan, V;Bredesen, DE
通讯作者：
Bredesen, DE
影响因子：
25
作者：
Cleary, JP;Walsh, DM;Ashe, KH
通讯作者：
Ashe, KH
影响因子：
3.5
作者：
CAMPION, D;FLAMAN, JM;FREBOURG, T
通讯作者：
FREBOURG, T
影响因子：
3.5
作者：
BAUMANN, K;MANDELKOW, EM;MANDELKOW, E
通讯作者：
MANDELKOW, E