New therapeutic targets in Alzheimer's disease: brain deregulation of calcium and zinc.
New therapeutic targets in Alzheimer's disease: brain deregulation of calcium and zinc.
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DOI：
10.1038/cddis.2011.57
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发表时间：
2011-06-23
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
阿尔茨海默病（AD）的分子决定因素仍然不完全清楚;然而，在过去的二十年中，大量的证据表明，该疾病的一个重要促成因素是两种信号阳离子：钙（Ca 2+）和锌（Zn 2+）的不平衡稳态的发展。这两种离子在中枢神经系统的生理功能中起着关键作用，但它们的大脑失调会促进淀粉样蛋白-β代谢异常以及tau磷酸化。AD还以改变的谷氨酸能激活为特征，并且谷氨酸可促进Ca 2+和Zn 2+稳态异常。这两种阳离子可以协同作用，促进自由基的产生，进一步细胞内Ca 2+和Zn 2+上升，并为自我维持的有害循环奠定基础。这些现象可能是导致AD的致病级联反应的初始步骤，因此，旨在预防Ca 2+和Zn 2+稳态异常的治疗干预可能为疾病改善策略提供很大的机会。
The molecular determinants of Alzheimer's (AD) disease are still not completely known; however, in the past two decades, a large body of evidence has indicated that an important contributing factor for the disease is the development of an unbalanced homeostasis of two signaling cations: calcium (Ca2+) and zinc (Zn2+). Both ions serve a critical role in the physiological functioning of the central nervous system, but their brain deregulation promotes amyloid-β dysmetabolism as well as tau phosphorylation. AD is also characterized by an altered glutamatergic activation, and glutamate can promote both Ca2+ and Zn2+ dyshomeostasis. The two cations can operate synergistically to promote the generation of free radicals that further intracellular Ca2+ and Zn2+ rises and set the stage for a self-perpetuating harmful loop. These phenomena can be the initial steps in the pathogenic cascade leading to AD, therefore, therapeutic interventions aiming at preventing Ca2+ and Zn2+ dyshomeostasis may offer a great opportunity for disease-modifying strategies.
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影响因子：
56.9
作者：
BUSH, AI;PETTINGELL, WH;TANZI, RE
通讯作者：
TANZI, RE
影响因子：
4.8
作者：
De Felice, Fernanda G.;Velasco, Pauline T.;Klein, William L.
通讯作者：
Klein, William L.
DOI：
10.1073/pnas.0702669104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Dong, Jijun;Canfield, Jeffrey M.;Lynn, David G.
通讯作者：
Lynn, David G.
影响因子：
9
作者：
通讯作者：
--
DOI：
10.1073/pnas.90.2.567
发表时间：
1993-01-15
影响因子：
11.1
作者：
ARISPE, N;ROJAS, E;POLLARD, HB
通讯作者：
POLLARD, HB