Gonzalez-Robles Cristina, Bandmann Oliver, Schapira Anthony H V
Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, S10 2HQ, UK.
Neurol Ther. 2025 Jul 18. doi: 10.1007/s40120-025-00793-z.
Parkinson disease (PD) is a progressive neurodegenerative condition characterised by tremor, bradykinesia and rigidity, as well as other motor and non-motor symptoms, for which no effective disease-modifying treatments have been discovered. Neuroprotection in PD is limited by its clinical and biological heterogeneity, suboptimal preclinical models, lack of established disease progression biomarkers, complex pathophysiology, the existence of effective symptomatic therapies which hamper the detection of actual disease modification, and trial design. This review discusses the above issues and other important concepts in neuroprotection in PD. The main pathophysiological mechanisms in PD are classified into mitochondrial dysfunction, lysosomal dysfunction, inflammation, protein aggregation/propagation, and "other", and discussed briefly. The most relevant disease-modifying candidates in PD are classified into the aforementioned categories and reviewed. Finally, conclusions and recommendations for future improvements in the field of disease modification in PD are provided.
帕金森病（PD）是一种进行性神经退行性疾病，其特征为震颤、运动迟缓、僵硬以及其他运动和非运动症状，目前尚未发现有效的疾病修饰治疗方法。帕金森病的神经保护受到其临床和生物学异质性、临床前模型欠佳、缺乏既定的疾病进展生物标志物、复杂的病理生理学、存在妨碍实际疾病修饰检测的有效对症疗法以及试验设计的限制。本综述讨论了上述问题以及帕金森病神经保护中的其他重要概念。帕金森病的主要病理生理机制分为线粒体功能障碍、溶酶体功能障碍、炎症、蛋白质聚集/传播以及“其他”，并进行了简要讨论。帕金森病中最相关的疾病修饰候选药物分为上述类别并进行了综述。最后，给出了关于帕金森病疾病修饰领域未来改进的结论和建议。
