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阿尔茨海默病中的细胞凋亡:对生理、病理及治疗途径的认识

Apoptosis in Alzheimer's disease: an understanding of the physiology, pathology and therapeutic avenues.

作者信息

Obulesu M, Lakshmi M Jhansi

机构信息

Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8573, Japan,

出版信息

Neurochem Res. 2014 Dec;39(12):2301-12. doi: 10.1007/s11064-014-1454-4. Epub 2014 Oct 17.

Abstract

Alzheimer's disease (AD) is a devastative neurodegenerative disorder with complex etiology. Apoptosis, a biological process that plays an essential role in normal physiology to oust a few cells and contribute to the normal growth, when impaired or influenced by various factors such as Bcl2, Bax, caspases, amyloid beta, tumor necrosis factor-α, amyloid precursor protein intracellular C-terminal domain, reactive oxygen species, perturbation of enzymes leads to deleterious neurodegenerative disorders like AD. There are diverse pathways that provoke manifold events in mitochondria and endoplasmic reticulum (ER) to execute the process of cell death. This review summarizes the crucial apoptotic mechanisms occurring in both mitochondria and ER. It gives substantial summary of the diverse mechanisms studied in vivo and in vitro. A brief account on neuroprotection of several bioactive components, flavonoids and antioxidants of plants against apoptotic events of both mitochondria and ER in both in vitro and in vivo has been discussed. In light of this, the burgeoning need to develop animal models to study the efficacy of various therapeutic effects has been accentuated.

摘要

阿尔茨海默病(AD)是一种病因复杂的毁灭性神经退行性疾病。细胞凋亡是一种在正常生理过程中发挥重要作用的生物学过程,它能清除一些细胞并促进正常生长,但当受到诸如Bcl2、Bax、半胱天冬酶、β淀粉样蛋白、肿瘤坏死因子-α、淀粉样前体蛋白细胞内C末端结构域、活性氧、酶的扰动等各种因素的损害或影响时,会导致像AD这样有害的神经退行性疾病。有多种途径会引发线粒体和内质网(ER)中的多种事件,从而执行细胞死亡过程。本综述总结了线粒体和内质网中发生的关键凋亡机制。它对体内和体外研究的多种机制进行了大量总结。还讨论了几种生物活性成分、植物类黄酮和抗氧化剂在体外和体内对线粒体和内质网凋亡事件的神经保护作用的简要情况。鉴于此,强调了开发动物模型以研究各种治疗效果有效性的迫切需求。

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