帕金森病的 AAV-α-Synuclein 模型:最新进展。

IF 4 3区 医学 Q2 NEUROSCIENCES
Anders Björklund, Bengt Mattsson
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引用次数: 0

摘要

自 AAV 载体问世以来的二十年间,它已发展成为一种多功能工具,可用于模拟帕金森病和相关路易体疾病中出现的突触核蛋白病的不同方面。病毒载体的疾病建模方法很有吸引力,因为α-突触核蛋白(野生型或突变型)的表达可以被限制在确定的解剖结构中,并利用细胞类型特异性启动子构建体或不同的天然或工程AAV血清型定向表达到选定的细胞群中。AAV-α-突触核蛋白最初用于模拟黑质多巴胺神经元中进行性α-突触核蛋白病理学,与标准的6-OHDA模型一样,它最常用于单侧应用,使用未注射的一侧作为参考和对照。但近年来,AAV-α-突触核蛋白模型已被更广泛地用于诱导其他相关神经元系统出现帕金森样突触核蛋白病变,如脑干去甲肾上腺素能神经元和5-羟色胺能神经元、迷走神经运动神经元以及少突胶质细胞,后者是多系统萎缩病变的主要靶点。本综述旨在概述过去二十年中使用 AAV-α 突触核蛋白模型所取得的进展,并总结使用 AAV-α 突触核蛋白模型对大鼠和小鼠进行疾病建模的最新进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The AAV-α-Synuclein Model of Parkinson's Disease: An Update.

Targeted delivery of α-synuclein using AAV vectors has over the two decades since its introduction developed into a versatile tool for modeling different aspects of synucleinopathy, mimicking those seen in Parkinson's disease and related Lewy body disorders. The viral vector approach to disease modeling is attractive in that the expression of α-synuclein, wild-type or mutated, can be confined to defined anatomical structures and targeted to selected cell populations using either cell-type specific promoter constructs or different natural or engineered AAV serotypes. AAV-α-synuclein was initially used to model progressive α-synuclein pathology in nigral dopamine neurons, and, like the standard 6-OHDA model, it has most commonly been applied unilaterally, using the non-injected side as a reference and control. In recent years, however, the AAV-α-synuclein model has become more widely used to induce Parkinson-like synuclein pathology in other relevant neuronal systems, such as the brainstem noradrenergic and serotonergic neurons, the vagal motor neurons, as well as in oligodendrocytes, the prime target relevant to the pathology seen in multiple system atrophy. The purpose of this review is to give an overview of the progress made in the use of the AAV-α-synuclein model over the last two decades and summarize the state-of-the art in the use of the AAV-α-synuclein model for disease modeling in rats and mice.

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来源期刊
CiteScore
8.40
自引率
5.80%
发文量
338
审稿时长
>12 weeks
期刊介绍: The Journal of Parkinson''s Disease (JPD) publishes original research in basic science, translational research and clinical medicine in Parkinson’s disease in cooperation with the Journal of Alzheimer''s Disease. It features a first class Editorial Board and provides rigorous peer review and rapid online publication.
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