Singh Gursimran, Aran Khadga Raj
Department of Pharmacy Practice, ISF College of Pharmacy, Moga, Punjab, 142001, India.
Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India.
Curr Neurovasc Res. 2026 Feb 19. doi: 10.2174/0115672026434365260113100943.
PD is a progressive neurodegenerative disorder, which is associated with the deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor symptoms. Pathogenesis includes alpha-synuclein aggregation and Lewy bodies, neuroinflammation, and oxidative stress. The breakdown of the blood-brain barrier (BBB) via tight junctions and disturbed transporter activity has been identified as a factor in the evolution of PD.
The review is a synthesis of evidence provided by preclinical and clinical studies that examine the connection between BBB dysfunction and the pathogenesis of PD. PubMed, Web of Science, and Google Scholar were used to source the literature, and studies that show BBB permeability, α-synuclein pathology, and therapeutic interventions of BBB integrity were used as a limiting factor.
Evidence indicates that the activation of BBB damage by disruptive activity allows the intrusion of neurotoxic factors and inflammatory agents in the central nervous system to worsen the degeneration of dopaminergic neurons. The changes in endothelial tight junction proteins, transporters, and immune cell infiltrations have remained consistent in PD models. Preclinical treatments, including neuroprotective therapeutics, anti-inflammatory medications, and treatments that alter the BBB permeability to be used in delivering drugs to specific brain locations, have demonstrated positive outcomes in the survival of neurons and motor activity.
BBB dysfunction in PD appears to be an outcome and a cause of neurodegeneration, which forms a vicious cycle with neuroinflammation and α-synuclein deposition. Modifying permeability by targeting BBB repair pathways and selecting particular mechanisms to enhance permeability are promising disease-modifying therapies.
BBB integrity is a very important but under-investigated element of PD pathogenesis. Understanding its interplay with neuroinflammation and protein aggregation may yield novel therapeutic targets and improve drug delivery approaches in PD management.
帕金森病（PD）是一种进行性神经退行性疾病，与黑质致密部（SNpc）中多巴胺能神经元的退化有关，导致运动和非运动症状。其发病机制包括α-突触核蛋白聚集和路易小体、神经炎症以及氧化应激。通过紧密连接破坏血脑屏障（BBB）以及转运体活性紊乱已被确定为PD进展中的一个因素。
本综述综合了临床前和临床研究提供的证据，这些研究探讨了血脑屏障功能障碍与PD发病机制之间的联系。使用PubMed、科学网和谷歌学术搜索文献，并将显示血脑屏障通透性、α-突触核蛋白病理学以及血脑屏障完整性治疗干预的研究作为限制因素。
证据表明，破坏活动激活血脑屏障损伤，使神经毒性因子和炎症介质侵入中枢神经系统，加剧多巴胺能神经元的退化。在PD模型中，内皮紧密连接蛋白、转运体和免疫细胞浸润的变化一直存在。临床前治疗，包括神经保护疗法、抗炎药物以及改变血脑屏障通透性以将药物输送到特定脑区的治疗，在神经元存活和运动活动方面已显示出积极结果。
PD中的血脑屏障功能障碍似乎是神经退行性变的结果和原因，与神经炎症和α-突触核蛋白沉积形成恶性循环。通过靶向血脑屏障修复途径改变通透性并选择特定机制增强通透性是有前景的疾病修饰疗法。
血脑屏障完整性是PD发病机制中一个非常重要但研究不足的因素。了解其与神经炎症和蛋白质聚集的相互作用可能会产生新的治疗靶点，并改善PD管理中的药物递送方法。
