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

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.