胰高血糖素样肽-1受体激动剂及其类似物在帕金森病中神经保护作用机制的研究进展

Progress in research on neuroprotective mechanism of glucagon-like peptide-1 receptor agonists and analogues in Parkinson's disease

帕金森病(Parkinson’s disease,PD)是好发于中老年人的第二大神经退行性疾病,目前一线治疗药物以左旋多巴为主,但患者长期服用疗效欠佳,甚至出现“开关”现象和直立性低血压等不良反应。胰高血糖素样肽-1受体激动剂(glucagon-like peptide-1 receptor agonist,GLP-1RA)及其类似物是一种内源性肽激素,释放至血液中可穿越血脑屏障进入中枢神经系统发挥神经保护作用。研究表明,GLP-1RA可改善PD的运动障碍并恢复多巴胺能神经元活性。但其起效机制尚未完全明确,本文归纳总结了GLP-1RA及其类似物改善PD运动障碍、恢复多巴胺能神经元活性的作用机制,从减少神经炎症、抑制氧化应激、抑制细胞凋亡、调节线粒体形态、增加神经元突起、增强自噬、调节肠道菌群稳态等方面作一综述,为PD机制的研究和GLP-1RA相关新药研发提供新思路。

Parkinson's disease(PD)is the second common neurodegenerative disease that mostly occurs in middle-aged and elderly people.Currently,Levodopa is the main first-line treatment drug,but the long-term efficacy of patients is not good,and even side effects such as"on-off"phenomenon and orthostatic hypotension occur.Glucagon-like peptide-1 receptor agonists(CLP-IRA)and analogues are endogenous peptide hormones that can be released into the blood and enter the central nervous system to exert neuroprotection by crossing the blood-brain barrier.Numerous studies have shown that GLP-1RA can improve movement disorders and restore dopaminergic neuron activity in PD.However,the mechanism of GLP-1RA is not yet fully clear.This paper summarized the mechanism of GLP-1RA and its analogues in improving PD movement disorders and restoring dopaminergic neuron activity,and reviewed the aspects of reducing neuroinflammation,inhibiting oxidative stress,inhibiting apoptosis,regulating mitochondrial morphology,increasing neuronal protrusions,enhancing autophagy,and regulating intestinal flora homeostasis,so as to provide new ideas for research of the mechanisms of PD and development of GLP-1RA-related new drugs.