Abstract：
Parkinsonism is the primary type of movement disorder in adults, encompassing a set of clinical symptoms, including rigidity, tremors, dystonia, bradykinesia, and postural instability. These symptoms are primarily caused by a deficiency in dopamine (DA), an essential neurotransmitter in the brain. Currently, the DA precursor levodopa (synthetic L-DOPA) is the standard medication to treat DA deficiency, but it only addresses symptoms rather than provides a cure. In this review, we provide an overview of disorders associated with DA dysregulation and deficiency, particularly Parkinson\'s disease and rare inherited disorders leading predominantly to dystonia and/or parkinsonism, even in childhood. Although levodopa is relatively effective for the management of motor dysfunctions, it is less effective for severe forms of parkinsonism and is also associated with side effects and a loss of efficacy over time. We present ongoing efforts to reinforce the effect of levodopa and to develop innovative therapies that target the underlying pathogenic mechanisms affecting DA synthesis and transport, increasing neurotransmission through disease-modifying approaches, such as cell-based therapies, nucleic acid- and protein-based biologics, and small molecules.
摘要：
帕金森病是成人运动障碍的主要类型，包括一组临床症状，包括刚性，震颤,肌张力障碍,运动迟缓,和姿势不稳定。这些症状主要是由多巴胺（DA）缺乏引起的，大脑中必不可少的神经递质。目前,DA前体左旋多巴（合成L-DOPA）是治疗DA缺乏症的标准药物，但它只解决症状，而不是提供治疗。在这次审查中,我们提供了与DA失调和缺乏相关的疾病的概述，特别是帕金森病和罕见的遗传性疾病，主要导致肌张力障碍和/或帕金森病，甚至在童年。尽管左旋多巴对运动功能障碍的管理相对有效，它对严重形式的帕金森综合征的疗效较差，并且随着时间的推移与副作用和疗效丧失有关。我们提出了正在进行的努力，以加强左旋多巴的作用，并开发针对影响DA合成和运输的潜在致病机制的创新疗法。通过改善疾病的方法增加神经传递，例如基于细胞的疗法，基于核酸和蛋白质的生物制品，和小分子。
