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胆汁酸与细胞凋亡调节:在实验性阿尔茨海默病中的新作用

Bile acids and apoptosis modulation: an emerging role in experimental Alzheimer's disease.

作者信息

Ramalho Rita M, Viana Ricardo J S, Low Walter C, Steer Clifford J, Rodrigues Cecília M P

机构信息

iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.

出版信息

Trends Mol Med. 2008 Feb;14(2):54-62. doi: 10.1016/j.molmed.2007.12.001. Epub 2008 Jan 22.

Abstract

The potential role of apoptosis in Alzheimer's disease (AD) has been an area of intense research in recent years. Ursodeoxycholic acid (UDCA) and its taurine-conjugate, tauroursodeoxycholic acid (TUDCA) are endogenous bile acids that act as potent inhibitors of apoptosis. Their therapeutic effects have been tested in many experimental pathological conditions, including neurological disorders, such as AD. TUDCA regulates precise transcriptional and post-transcriptional events that impact mitochondrial function in neurons. TUDCA not only stabilizes the mitochondrial membrane and prevents Bax translocation, inhibiting the release of cytochrome c and the activation of caspases, but also interferes with upstream factors, including cell cycle-related proteins. In addition, TUDCA is capable of inducing survival pathways. Here, we review the role of apoptosis in AD and discuss the therapeutic potential of TUDCA in treating this disease.

摘要

近年来,细胞凋亡在阿尔茨海默病(AD)中的潜在作用一直是研究的热点领域。熊去氧胆酸(UDCA)及其与牛磺酸结合的产物牛磺熊去氧胆酸(TUDCA)是内源性胆汁酸,可作为细胞凋亡的有效抑制剂。它们的治疗效果已在许多实验性病理条件下进行了测试,包括神经疾病,如AD。TUDCA调节影响神经元线粒体功能的精确转录和转录后事件。TUDCA不仅能稳定线粒体膜并阻止Bax易位,抑制细胞色素c的释放和半胱天冬酶的激活,还能干扰上游因子,包括细胞周期相关蛋白。此外,TUDCA能够诱导生存途径。在此,我们综述细胞凋亡在AD中的作用,并讨论TUDCA治疗该疾病的潜在治疗价值。

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