Alteration of caspases and apoptosis-related proteins in brains of patients with Alzheimer's disease
Alteration of caspases and apoptosis-related proteins in brains of patients with Alzheimer's disease
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DOI：
10.1006/bbrc.2001.4306
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发表时间：
2001-02-16
影响因子：
3.1
通讯作者：
Lubec, G
中科院分区：
文献类型：
--
作者：
Engidawork, E;Gulesserian, T;Lubec, G
失调的程序性细胞死亡或凋亡Al阿尔茨海默病（AD）。半胱天冬酶是一种半胱氨酸蛋白酶，它能在天冬氨酸残基后切割关键底物蛋白，被认为是参与细胞凋亡tors发病机制的主要作用。半胱天冬酶的活性受到具有不同蛋白质-蛋白质相互作用结构域的多种蛋白质的精细调节。为了进一步证实细胞凋亡在AD中的作用，我们通过Western印迹技术研究了对照组和AD受试者额叶皮层和小脑中参与细胞凋亡的9种不同蛋白的水平。在AD中，caspase-3、-8和-9、DFF 45（DNA片段化因子45）和FLIP（Fas相关死亡结构域（FADD）样白细胞介素-1 β转化酶抑制蛋白）的蛋白水平降低，而ARC（具有caspase募集结构域的凋亡抑制因子）和RICK（受体相互作用蛋白（RIP）样相互作用的ILIP激酶）的蛋白水平升高。相反，细胞色素c和Apaf-1（凋亡蛋白酶激活因子-1）没有变化。回归分析显示，蛋白质水平和死亡时间之间没有相关性。然而，不一致的相关性之间的年龄和蛋白质的水平，以及个别蛋白质的水平。目前的研究结果表明，凋亡蛋白的失调确实存在于AD的大脑和支持的概念，它可能有助于AD的神经病理学。该研究进一步提示AD中的细胞凋亡可能通过不依赖于细胞色素c的死亡受体途径发生。因此，消融半胱天冬酶激活的治疗策略可能对AD患者有一定益处。(C)北京：科学出版社.
Dysregulated programmed cell death or apoptosis Al Alzheimer's disease (AD). Caspases, the major effects suggested to be involved in the pathogenesis of tors of apoptosis, are cysteine proteases that cleave crucial substrate proteins exclusively after aspartate residues. The activity of caspases are delicately regulated by a variety of proteins that possess distinct domains for protein-protein interaction. To further substantiate the role of apoptosis in AD, we investigated the levels of nine different proteins involved in apoptosis by Western blot technique in frontal cortex and cerebellum of control and AD subjects. The protein levels of caspase-3, -8, and -9, DFF45 (DNA fragmentation factor 45), and FLIP (Fas associated death domain (FADD)-like interleukin-1 beta -converting enzyme inhibitory proteins) were decreased, whereas those of ARC (apoptosis repressor with caspase recruitment domain) and RICK (Receptor interacting protein (RIP)-like interacting CLARP kinase) increased in AD. In contrast;, cytochrome c and Apaf-1 (apoptosis protease activating factor-1) were unchanged. Regression analysis revealed no correlation between levels of protein and postmortem interval. However, inconsistent correlation was found between age and levels of proteins as well as among the levels of individual proteins. The current findings showed that dysregulation of apoptotic proteins indeed exists in AD brain and support the notion that it may contribute to neuropathology of AD. The study further hints that apoptosis in AD may occur via the death receptor pathway independent of cytochrome c. Hence, therapeutic strategies that ablate caspase activation may be of some benefit for AD sufferers. (C) 2001 Academic Press.