Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Brain Res Bull. 2012 May 1;88(1):13-32. doi: 10.1016/j.brainresbull.2011.07.019. Epub 2011 Aug 3.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting more than 1% of the population over age 60. The most common feature of PD is a resting tremor, though there are many systemic neurological effects, such as incontinence and sleep disorders. PD is histopathologically identified by the presence of Lewy bodies (LB), proteinaceous inclusions constituted primarily by α-synuclein. To date, there is no effective treatment to slow or stop disease progression. To help understand disease pathogenesis and identify potential therapeutic targets, many genetic mouse models have been developed. By far the most common of these models are the wildtype and mutant α-synuclein transgenic mice, because α-synuclein was the first protein shown to have a direct effect on PD pathogenesis and progression. There are many other gene-disrupted or -mutated models currently available, which are based on genetic anomalies identified in the human disease. In addition, there are also models which examine genes that may contribute to disease onset or progression but currently have no identified causative PD mutations. These genes are part of signaling pathways important for maintaining neuronal function in the nigrostriatal pathway. This review will summarize the most commonly used of the genetic mouse models currently available for PD research. We will examine how these models have expanded our understanding of PD pathogenesis and progression, as well as aided in identification of potential therapeutic targets in this disorder.
帕金森病（PD）是最常见的神经退行性运动障碍，影响超过 60 岁的人群的 1%以上。PD 的最常见特征是静止性震颤，但也有许多全身性神经系统影响，如失禁和睡眠障碍。PD 在组织病理学上通过Lewy 体（LB）的存在来识别，LB 是由α-突触核蛋白组成的蛋白包涵体。迄今为止，尚无有效的治疗方法可以减缓或阻止疾病进展。为了帮助理解疾病发病机制并确定潜在的治疗靶点，已经开发了许多遗传小鼠模型。到目前为止，这些模型中最常见的是野生型和突变型α-突触核蛋白转基因小鼠，因为α-突触核蛋白是第一个被证明对 PD 发病机制和进展有直接影响的蛋白质。目前还有许多其他基因缺失或突变的模型，这些模型基于在人类疾病中发现的遗传异常。此外，还有一些模型研究可能导致疾病发作或进展的基因，但目前没有确定的导致 PD 的突变。这些基因是对黑质纹状体通路中维持神经元功能很重要的信号通路的一部分。这篇综述将总结目前可用于 PD 研究的最常用的遗传小鼠模型。我们将研究这些模型如何扩展我们对 PD 发病机制和进展的理解，并有助于确定该疾病的潜在治疗靶点。
