Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.
K.G. Jebsen Center for Translational Research in Parkinson's Disease, University of Bergen, 5020 Bergen, Norway.
Biochem Soc Trans. 2024 Jun 26;52(3):1275-1291. doi: 10.1042/BST20231061.
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.
帕金森病是成年人中主要的运动障碍类型，包括一组临床症状，包括僵硬、震颤、肌张力障碍、运动迟缓以及姿势不稳。这些症状主要是由于大脑中一种重要的神经递质多巴胺（DA）的缺乏引起的。目前，DA 前体左旋多巴（合成 L-DOPA）是治疗 DA 缺乏的标准药物，但它只能解决症状，而不能治愈。在这篇综述中，我们概述了与 DA 调节和缺乏相关的疾病，特别是帕金森病和罕见的遗传性疾病，这些疾病主要导致肌张力障碍和/或帕金森病，甚至在儿童时期。虽然左旋多巴对于运动功能障碍的治疗相对有效，但对于严重的帕金森病形式效果较差，并且随着时间的推移还会出现副作用和疗效丧失。我们介绍了正在进行的努力，以加强左旋多巴的效果，并开发针对影响 DA 合成和转运的潜在致病机制的创新疗法，通过疾病修饰方法增加神经传递，例如基于细胞的疗法、核酸和蛋白质生物制剂以及小分子。
