Genetic mouse models of parkinsonism: strengths and limitations.
Genetic mouse models of parkinsonism: strengths and limitations.
复制标题
DOI：
10.1602/neurorx.2.3.495
复制
发表时间：
2005-07-01
期刊：
影响因子：
--
通讯作者：
Chesselet, Marie-Francoise
中科院分区：
文献类型：
--
作者：
Fleming, Sheila M;Fernagut, Pierre-Olivier;Chesselet, Marie-Francoise
帕金森病（PD）是一种进行性神经退行性疾病。 PD 患者表现出多种运动症状，包括静息性震颤、强直、运动迟缓和姿势不稳，这些症状会随着时间的推移而恶化。这些运动症状与黑质致密部多巴胺神经元的逐渐丧失有关。 PD 患者还患有非运动症状，这些症状可能先于主要运动症状，并且可能与其他大脑区域的病理有关。传统的帕金森毒素模型主要关注黑质纹状体通路和该区域多巴胺神经元的丧失，这些模型对于我们了解帕金森病和开发该疾病的对症治疗方法非常重要。然而，它们的局限性在于它们不能再现 PD 中看到的完整病理学和进展，因此需要更好的模型。最近发现的引起家族性帕金森病的特定基因促进了新型帕金森病遗传小鼠模型的开发。本综述讨论了这些新模型的有效性、优点和局限性。
Parkinson's disease (PD) is a progressive neurodegenerative disorder. Patients with PD display a combination of motor symptoms including resting tremor, rigidity, bradykinesia, and postural instability that worsen over time. These motor symptoms are related to the progressive loss of dopamine neurons in the substantia nigra pars compacta. PD patients also suffer from nonmotor symptoms that may precede the cardinal motor symptoms and that are likely related to pathology in other brain regions. Traditional toxin models of PD have focused on the nigrostriatal pathway and the loss of dopamine neurons in this region, and these models have been important in our understanding of PD and in the development of symptomatic treatments for the disease. However, they are limited in that they do not reproduce the full pathology and progression seen in PD, thus creating a need for better models. The recent discovery of specific genes causing familial forms of PD has contributed to the development of novel genetic mouse models of PD. This review discusses the validity, benefits, and limitations of these new models.