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帕金森病中涉及的基因、蛋白质和神经毒素。

Genes, proteins, and neurotoxins involved in Parkinson's disease.

作者信息

von Bohlen und Halbach O, Schober A, Krieglstein K

机构信息

Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 307, D-69120 Heidelberg, Germany.

出版信息

Prog Neurobiol. 2004 Jun;73(3):151-77. doi: 10.1016/j.pneurobio.2004.05.002.

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder. The etiology of PD is likely due to combinations of environmental and genetic factors. In addition to the loss of neurons, including dopaminergic neurons in the substantia nigra pars compacta, a further morphologic hallmark of PD is the presence of Lewy bodies and Lewy neurites. The formation of these proteinaceous inclusions involves interaction of several proteins, including alpha-synuclein, synphilin-1, parkin and UCH-L1. Animal models allow to get insight into the mechanisms of several symptoms of PD, allow investigating new therapeutic strategies and, in addition, provide an indispensable tool for basic research. In animals PD does not arise spontaneously, thus, characteristic and specific functional changes have to be mimicked by application of neurotoxic agents or by genetic manipulations. In this review we will focus on genes and gene loci involved in PD, the functions of proteins involved in the formation of cytoplasmatic inclusions, their interactions, and their possible role in PD. In addition, we will review the current animal models of PD.

摘要

帕金森病(PD)是一种常见的神经退行性疾病。PD的病因可能是环境因素和遗传因素共同作用的结果。除了神经元丧失,包括黑质致密部的多巴胺能神经元,PD的另一个形态学特征是路易小体和路易神经突的存在。这些蛋白质内含物的形成涉及多种蛋白质的相互作用,包括α-突触核蛋白、突触核蛋白-1、帕金蛋白和泛素羧基末端水解酶L1(UCH-L1)。动物模型有助于深入了解PD的几种症状的机制,有助于研究新的治疗策略,此外,还为基础研究提供了不可或缺的工具。在动物中,PD不会自发产生,因此,必须通过应用神经毒性剂或基因操作来模拟其特征性和特异性功能变化。在这篇综述中,我们将重点关注与PD相关的基因和基因座、参与细胞质内含物形成的蛋白质的功能、它们之间的相互作用以及它们在PD中可能发挥的作用。此外,我们还将综述目前的PD动物模型。

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