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Abstract：
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.
Misfolding of the neuronal protein α-synuclein is central to the cellular processes that underlie the development of Parkinson’s disease and related disorders, such as dementia with Lewy bodies and multiple system atrophy. Targeted delivery of α-synuclein using adeno-associated virus, AAV, has become a standard tool to model the disease process in animals. This AAV-α-synuclein model of Parkinson’s disease was introduced two decades ago and over the ensuing decades it has become a widely used standard tool for experimental studies in animals. The usefulness of the AAV-α-synuclein model is largely due to its flexibility and versatility as an experimental tool. In this review the authors summarize the state-of-the art in this field and review the range of applications that has been developed using AAV-α-synuclein alone, in single hit models, or in combinations with other interacting risk factors, in double hit models.
Misfolding of the neuronal protein α-synuclein is central to the cellular processes that underlie the development of Parkinson’s disease and related disorders, such as dementia with Lewy bodies and multiple system atrophy. Targeted delivery of α-synuclein using adeno-associated virus, AAV, has become a standard tool to model the disease process in animals. This AAV-α-synuclein model of Parkinson’s disease was introduced two decades ago and over the ensuing decades it has become a widely used standard tool for experimental studies in animals. The usefulness of the AAV-α-synuclein model is largely due to its flexibility and versatility as an experimental tool. In this review the authors summarize the state-of-the art in this field and review the range of applications that has been developed using AAV-α-synuclein alone, in single hit models, or in combinations with other interacting risk factors, in double hit models.
摘要：
自AAV载体靶向递送α-突触核蛋白以来，其已发展成为模拟突触核蛋白病不同方面的通用工具。模仿在帕金森病和相关路易体病中看到的那些。病毒载体方法的疾病建模是有吸引力的，因为α-突触核蛋白的表达，野生型或突变，可以局限于限定的解剖结构,并使用细胞类型特异性启动子构建体或不同的天然或工程化AAV血清型靶向选择的细胞群体。AAV-α-突触核蛋白最初用于模拟黑色多巴胺神经元中的进行性α-突触核蛋白病理学，and,像标准的6-OHDA模型，它最常见的是单方面应用，使用非注入侧作为参考和控制。近年来,然而,AAV-α-突触核蛋白模型已更广泛地用于诱导其他相关神经元系统中的帕金森样突触核蛋白病理，如脑干的去甲肾上腺素能和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，与多系统萎缩中看到的病理相关的主要目标。这篇综述的目的是概述过去二十年来在使用AAV-α-突触核蛋白模型方面取得的进展，并总结使用AAV-α-突触核蛋白模型在大鼠和小鼠疾病建模中的最新技术。
神经元蛋白α-突触核蛋白的错误折叠是帕金森病和相关疾病发展的细胞过程的核心，如路易体痴呆和多系统萎缩。使用腺相关病毒靶向递送α-突触核蛋白，AAV,已经成为模拟动物疾病过程的标准工具。这种帕金森病的AAV-α-突触核蛋白模型是在20年前引入的，在随后的几十年中，它已成为动物实验研究的广泛使用的标准工具。AAV-α-突触核蛋白模型的有用性很大程度上归因于其作为实验工具的灵活性和多功能性。在这篇综述中，作者总结了该领域的最新技术，并回顾了单独使用AAV-α-突触核蛋白开发的应用范围。在单一命中模型中，或与其他相互作用的风险因素相结合，双命中模型。
神经元蛋白α-突触核蛋白的错误折叠是帕金森病和相关疾病发展的细胞过程的核心，如路易体痴呆和多系统萎缩。使用腺相关病毒靶向递送α-突触核蛋白，AAV,已经成为模拟动物疾病过程的标准工具。这种帕金森病的AAV-α-突触核蛋白模型是在20年前引入的，在随后的几十年中，它已成为动物实验研究的广泛使用的标准工具。AAV-α-突触核蛋白模型的有用性很大程度上归因于其作为实验工具的灵活性和多功能性。在这篇综述中，作者总结了该领域的最新技术，并回顾了单独使用AAV-α-突触核蛋白开发的应用范围。在单一命中模型中，或与其他相互作用的风险因素相结合，双命中模型。
