Neuroprotective effect of metformin on dopaminergic neurodegeneration and α-synuclein aggregation in C. elegans model of Parkinson's disease

Abstract

• Parkinson's disease (PD), the second most progressive neurodegenerative disease causing motor impairment and defective cognitive function, has been a burden to the quality of life for decades and remain incurable. Metformin, a biguanide anti-diabetic drugs for type 2 diabetes mellitus, recently exhibits a neuroprotective effect in many neurological disorders. Ultimately, the aim of the study was to elucidate the neuroprotective effects of metformin against PD in C. elegans models of 6-hydroxydopamine-induced dopaminergic neurodegeneration and α-synuclein protein aggregation. Our experiments showed that 10 mM metformin significantly decreased neurodegeneration in 6-hydroxydopamine-induced worms, and recovered its food-sensing behavior without an affect to the nematode development. Moreover, 10 mM metformin also inhibited α-synuclein aggregation and recovered the lipid deposition. Gene expression analysis revealed that metformin could upregulate cat-2 gene expression and GFP-tagged SOD-3 expression. However, metformin did not significantly alter mean or maximum lifespan of the PD model organism. Therefore, this study highlighted the neuroprotective effects of metformin on dopaminergic neurons and α-synuclein, while its precise mechanism should be conducted in the future.