Kim Tae Young, Lee Byoung Dae
Department of Neuroscience, Kyung Hee University, Seoul, South Korea.
Department of Neuroscience, Kyung Hee University, Seoul, South Korea; Department of Physiology, Kyung Hee University School of Medicine, Seoul, South Korea.
Mol Cells. 2025 Sep 4;48(11):100274. doi: 10.1016/j.mocell.2025.100274.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of misfolded α-synuclein. Current treatments, including dopaminergic medications and deep brain stimulation, provide symptomatic relief but do not halt disease progression. Recent advances in molecular research have enabled the development of disease-modifying strategies targeting key pathogenic mechanisms, such as α-synuclein aggregation, mitochondrial dysfunction, and genetic mutations, including LRRK2 and GBA1. In parallel, pluripotent stem cell-derived dopaminergic neurons have emerged as a scalable and ethically viable source for cell replacement therapy. Early-phase clinical trials have demonstrated the safety and functional integration of these grafts. Ongoing research is now focused on enhancing graft purity, immune compatibility, and anatomical precision, including homotopic transplantation and circuit-level reconstruction. Together, these emerging strategies offer the potential to shift PD treatment paradigms by combining symptomatic control with long-term neural restoration. This review summarizes current therapeutic approaches and highlights recent advances in disease-modifying and regenerative interventions for PD.
帕金森病(PD)是一种进行性神经退行性疾病,其特征是多巴胺能神经元丧失以及错误折叠的α-突触核蛋白积累。目前的治疗方法,包括多巴胺能药物和深部脑刺激,可缓解症状,但无法阻止疾病进展。分子研究的最新进展使得针对关键致病机制(如α-突触核蛋白聚集、线粒体功能障碍以及包括LRRK2和GBA1在内的基因突变)的疾病修饰策略得以发展。与此同时,多能干细胞衍生的多巴胺能神经元已成为细胞替代治疗中一种可扩展且符合伦理的可行细胞来源。早期临床试验已证明这些移植的安全性和功能整合。目前正在进行的研究集中在提高移植纯度、免疫相容性和解剖学精确性,包括同位移植和回路水平重建。总之,这些新兴策略有可能通过将症状控制与长期神经修复相结合来改变PD的治疗模式。本综述总结了当前的治疗方法,并重点介绍了PD疾病修饰和再生干预的最新进展。