Lv Dongliang, Feng Peng, Guan Xueying, Liu Zhaona, Li Dongfang, Xue Cunshui, Bai Bo, Hölscher Christian
Second Hospital, Shanxi Medical University, Taiyuan, China.
Henan Academy of Innovations in Medical Science, Brain Institute, Zhengzhou, China.
Front Neurol. 2024 Dec 10;15:1462240. doi: 10.3389/fneur.2024.1462240. eCollection 2024.
Parkinson's disease (PD) is a chronic, progressive neurological disorder primarily affecting motor control, clinically characterized by resting tremor, bradykinesia, rigidity, and other symptoms that significantly diminish the quality of life. Currently, available treatments only alleviate symptoms without halting or delaying disease progression. There is a significant association between PD and type 2 diabetes mellitus (T2DM), possibly due to shared pathological mechanisms such as insulin resistance, chronic inflammation, and mitochondrial dysfunction. PD is caused by a deficiency of dopamine, a neurotransmitter in the brain that plays a critical role in the control of movement. Glucose metabolism and energy metabolism disorders also play an important role in the pathogenesis of PD. This review investigates the neuroprotective mechanisms of glucagon-like peptide-1 (GLP-1) and its receptor agonists, offering novel insights into potential therapeutic strategies for PD. GLP-1 class drugs, primarily used in diabetes management, show promise in addressing PD's underlying pathophysiological mechanisms, including energy metabolism and neuroprotection. These drugs can cross the blood-brain barrier, improve insulin resistance, stabilize mitochondrial function, and enhance neuronal survival and function. Additionally, they exhibit significant anti-inflammatory and antioxidative stress effects, which are crucial in neurodegenerative diseases like PD. Research indicates that GLP-1 receptor agonists could improve both motor and cognitive symptoms in PD patients, marking a potential breakthrough in PD treatment and prevention. Further exploration of GLP-1's molecular mechanisms in PD could provide new preventive and therapeutic approaches, especially for PD patients with concurrent T2DM. By targeting both metabolic and neurodegenerative pathways, GLP-1 receptor agonists represent a multifaceted approach to PD treatment, offering hope for better disease management and improved patient outcomes.
帕金森病（PD）是一种慢性进行性神经疾病，主要影响运动控制，临床特征为静止性震颤、运动迟缓、肌强直以及其他显著降低生活质量的症状。目前，现有的治疗方法仅能缓解症状，无法阻止或延缓疾病进展。PD与2型糖尿病（T2DM）之间存在显著关联，这可能是由于胰岛素抵抗、慢性炎症和线粒体功能障碍等共同的病理机制所致。PD是由大脑中一种对运动控制起关键作用的神经递质多巴胺缺乏引起的。葡萄糖代谢和能量代谢紊乱在PD的发病机制中也起着重要作用。本综述研究了胰高血糖素样肽-1（GLP-1）及其受体激动剂的神经保护机制，为PD的潜在治疗策略提供了新的见解。主要用于糖尿病管理的GLP-1类药物在解决PD的潜在病理生理机制（包括能量代谢和神经保护）方面显示出前景。这些药物可以穿过血脑屏障，改善胰岛素抵抗，稳定线粒体功能，并增强神经元的存活和功能。此外，它们还具有显著的抗炎和抗氧化应激作用，这在PD等神经退行性疾病中至关重要。研究表明，GLP-1受体激动剂可以改善PD患者的运动和认知症状，这标志着PD治疗和预防方面的一个潜在突破。进一步探索GLP-1在PD中的分子机制可以提供新的预防和治疗方法，特别是对于合并T2DM的PD患者。通过针对代谢和神经退行性途径，GLP-1受体激动剂代表了一种多方面的PD治疗方法，为更好地管理疾病和改善患者预后带来了希望。
