The Effect of Metformin on Astrocytes in Parkinson's Disease: Challenges and Opportunities.

IF 4.3 2区医学 Q1 NEUROSCIENCES

Molecular Neurobiology Pub Date : 2025-11-01 Epub Date: 2025-06-04 DOI:10.1007/s12035-025-05098-8

Hayder M Al-Kuraishy, Ghassan M Sulaiman, Hebatallah M Saad, Hamdoon A Mohammed, Mosleh M Abomughaid, Ali I Al-Gareeb, Ali K Albuhadily

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引用次数: 0

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease that represents the most common movement disorder in old-age subjects. The development of PD neuropathology is due to the progressive accumulation of alpha-synuclein (α-Syn) in the dopaminergic neurons of the substantia nigra pars compacta (SNpc). Moreover, astrocytes are intricate in the pathogenesis of PD that has neuroprotective effects against oxidative stress in PD by releasing antioxidant and anti-inflammatory mediators. The physiological properties of astrocytes are altered in PD due to the progressive accumulation of α-Syn, which induces mitochondrial dysfunction, oxidative stress, and inflammation. In addition, genetic mutations in PD also impact the antioxidant and anti-inflammatory properties of astrocytes. The functional role of astrocytes is extremely distorted in PD. Therefore, restoration of the anti-inflammatory and antioxidant effects of astrocytes could be an alternative therapeutic strategy in the management of PD. It has been shown that the anti-diabetic metformin improves the anti-inflammatory and antioxidant effects of astrocytes in different neurodegenerative diseases, including PD. Nevertheless, the mechanisms that relate to the effect of metformin on astrocytes in PD are not completely elucidated. Consequently, this review aims to discuss the astroprotective effect of metformin in PD with regard to the underlying mechanisms.

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二甲双胍对帕金森病星形胶质细胞的影响：挑战与机遇。

帕金森病（PD）是一种进行性神经退行性疾病，是老年人最常见的运动障碍。PD神经病理的发展是由于黑质致密部（SNpc）多巴胺能神经元中α-突触核蛋白（α-Syn）的进行性积累。此外，星形胶质细胞在PD的发病机制中错综复杂，通过释放抗氧化和抗炎介质对PD的氧化应激具有神经保护作用。PD患者星形胶质细胞的生理特性由于α-Syn的逐渐积累而发生改变，从而导致线粒体功能障碍、氧化应激和炎症。此外，PD基因突变也会影响星形胶质细胞的抗氧化和抗炎特性。星形胶质细胞的功能作用在PD中严重扭曲。因此，恢复星形胶质细胞的抗炎和抗氧化作用可能是PD治疗的一种替代治疗策略。研究表明，抗糖尿病的二甲双胍可改善星形胶质细胞在包括帕金森病在内的不同神经退行性疾病中的抗炎和抗氧化作用。然而，二甲双胍对PD患者星形胶质细胞的作用机制尚未完全阐明。因此，本文旨在探讨二甲双胍对帕金森病的保护作用及其潜在机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Neurobiology 医学-神经科学

CiteScore

9.00

自引率

2.00%

发文量

480

审稿时长

1 months

期刊介绍： Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.