Khalid Iqbal Muhammad, Khan Bakhtawar, YuXuan Ge, Mujahid Muhammad, Kiyani Mubin Mustafa, Khan Hamid, Bashir Shahid
Institute of Brain Disorders, Department of Physiology, Dalian Medical University, Dalian, Liaoning Province 116044, China.
Department of Biochemistry, Government College University, Faisalabad 38000, Pakistan.
ACS Omega. 2024 Nov 5;9(46):45663-45672. doi: 10.1021/acsomega.4c06546. eCollection 2024 Nov 19.
Parkinson's disease (PD) is a brain disorder in which neuronal cells responsible for the release of dopamine, a neurotransmitter that controls movement, are degenerated or impaired in the substantia nigra and basal ganglia. The disease typically affects people over the age of 5 and presents with a variety of motor and nonmotor dysfunctions, which are unique to each person. The impairment of the blood-brain barrier (BBB) and blood retinal barrier (BRB) due to age-related causes such as weakness of tight junctions or rare genetic factors allows several metabolic intermediates to reach and accumulate inside neurons such as Lewy bodies and α-synuclein, disrupting neuronal homeostasis and leading to genetic and epigenetic changes, e.g., damage to the DNA repair system. This perspective highlights the importance of blood barriers, such as the BBB and BRB, in the progression of PD, as the aggregation of Lewy bodies and α-synuclein disrupts neuronal homeostasis. Genetic and epigenetic factors, neuroinflammation, oxidative stress, and mitochondrial dysfunction play crucial roles in the progression of the disease. The implications of these findings are significant; identifying synaptic dysfunction could lead to earlier diagnosis and treatment, while developing targeted therapies focused on preserving synaptic function may slow or halt disease progression. Understanding the various genetic forms of PD could enable more personalized medicine approaches, and using patient-derived midbrain neurons for research may improve the accuracy of PD models due to the implications of an impaired BBB.
帕金森病（PD）是一种脑部疾病，其中负责释放多巴胺（一种控制运动的神经递质）的神经元细胞在黑质和基底神经节中发生退化或受损。该疾病通常影响50岁以上的人群，并表现出各种运动和非运动功能障碍，每个人的症状都有所不同。由于紧密连接减弱或罕见遗传因素等与年龄相关的原因导致血脑屏障（BBB）和血视网膜屏障（BRB）受损，使得几种代谢中间体能够到达并积聚在神经元内部，如路易小体和α-突触核蛋白，破坏神经元内环境稳定并导致基因和表观遗传变化，例如DNA修复系统受损。这一观点强调了血屏障（如BBB和BRB）在PD进展中的重要性，因为路易小体和α-突触核蛋白的聚集会破坏神经元内环境稳定。遗传和表观遗传因素、神经炎症、氧化应激和线粒体功能障碍在该疾病的进展中起着关键作用。这些发现的意义重大；识别突触功能障碍可能导致早期诊断和治疗，而开发专注于保护突触功能的靶向疗法可能会减缓或阻止疾病进展。了解PD的各种遗传形式可以实现更个性化的医学方法，并且由于BBB受损的影响，使用患者来源的中脑神经元进行研究可能会提高PD模型的准确性。
