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神经退行性疾病中的受体

Receptors in neurodegenerative diseases.

作者信息

Froestl W

机构信息

NOVARTIS Pharma, Therapeutic Area Nervous System, Basel, Switzerland.

出版信息

Pharm Acta Helv. 2000 Mar;74(2-3):247-51. doi: 10.1016/s0031-6865(99)00035-7.

Abstract

The ability of trophic factors to regulate developmental neuronal survival and adult nervous system plasticity suggests the use of these molecules to treat neurodegeneration associated with human diseases, such as Alzheimer's, Huntington's and Parkinson's disease, of amyotrophic lateral sclerosis and peripheral sensory neuropathies. Recent biological data on the neutrotrophins NGF and BDNF, on GDNF, CNTF and IGF-I are discussed together with first results from clinical trials. Literature is presented on the three-dimensional structures of these trophic factors and on models proposed for ligand-receptor interactions. Substantial progress has been made in the understanding of the mechanisms of apoptosis. The cascade consisting of interaction of apoptosis-inducing ligands with death receptors, the coupling of this complex to adaptor proteins via death domains, the further recruitment of procaspases via death effector or caspase recruitment domains and the execution of cell death via the effector caspases is briefly outlined.

摘要

营养因子调节发育中神经元存活及成体神经系统可塑性的能力,提示可利用这些分子治疗与人类疾病相关的神经退行性变,如阿尔茨海默病、亨廷顿病、帕金森病、肌萎缩侧索硬化症及周围感觉神经病。本文讨论了神经营养因子NGF和BDNF、GDNF、CNTF及IGF-I的最新生物学数据,以及临床试验的初步结果。还介绍了这些营养因子的三维结构及所提出的配体-受体相互作用模型的相关文献。在对凋亡机制的理解方面已取得了实质性进展。简要概述了由凋亡诱导配体与死亡受体相互作用、该复合物通过死亡结构域与衔接蛋白偶联、通过死亡效应结构域或半胱天冬酶募集结构域进一步募集前体半胱天冬酶以及通过效应半胱天冬酶执行细胞死亡所组成的级联反应。

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