Laboratório de Bioquímica Celular, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-003, Brazil.
Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London, SE1 9NH, UK.
Neuromolecular Med. 2017 Sep;19(2-3):241-255. doi: 10.1007/s12017-017-8454-x. Epub 2017 Jul 18.
Parkinson's disease (PD) is the second most common neurodegenerative disorder and has both unknown etiology and non-curative therapeutic options. Patients begin to present the classic motor symptoms of PD-tremor at rest, bradykinesia and rigidity-once 50-70% of the dopaminergic neurons of the nigrostriatal pathway have degenerated. As a consequence of this, it is difficult to investigate the early-stage events of disease pathogenesis. In vitro experimental models are used extensively in PD research because they present a controlled environment that enables the direct investigation of the early molecular mechanisms that are potentially involved with dopaminergic degeneration, as well as for the screening of potential therapeutic drugs. However, the establishment of PD in vitro models is a controversial issue for neuroscience research not only because it is challenging to mimic, in isolated cell systems, the physiological neuronal environment, but also the pathophysiological conditions experienced by human dopaminergic cells in vivo during the progression of the disease. Since no previous work has attempted to systematically review the literature regarding the establishment of an optimal in vitro model, and/or the features presented by available models used in the PD field, this review aims to summarize the merits and limitations of the most widely used dopaminergic in vitro models in PD research, which may help the PD researcher to choose the most appropriate model for studies directed at the elucidation of the early-stage molecular events underlying PD onset and progression.
帕金森病（PD）是第二常见的神经退行性疾病，其病因不明，治疗方法也不可治愈。一旦黑质纹状体通路中 50-70%的多巴胺能神经元发生退化，患者就会开始出现 PD 的典型运动症状——静止性震颤、运动迟缓以及僵硬。因此，很难研究疾病发病机制的早期事件。体外实验模型在 PD 研究中被广泛应用，因为它们提供了一个可控的环境，可以直接研究潜在涉及多巴胺能退化的早期分子机制，并筛选潜在的治疗药物。然而，体外建立 PD 模型对于神经科学研究来说是一个有争议的问题，不仅因为在孤立的细胞系统中模拟生理神经元环境具有挑战性，而且还因为在疾病进展过程中，体内人类多巴胺能细胞经历的病理生理条件也具有挑战性。由于以前没有人尝试系统地回顾关于建立最佳体外模型的文献，以及/或 PD 领域中可用模型的特征，因此，本综述旨在总结最广泛用于 PD 研究的多巴胺能体外模型的优缺点，这可能有助于 PD 研究人员选择最适合用于阐明 PD 发病和进展的早期分子事件的研究模型。
