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

Parkinsons 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 alpha-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 alpha-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 alpha-synuclein, while its precise mechanism should be conducted in the future. (C) 2019 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

Automated summary

The study demonstrated that metformin has significant neuroprotective effects on dopaminergic neurons and alpha-synuclein in a Parkinson's disease model, reducing neurodegeneration, inhibiting protein aggregation, and impacting gene expression, while not affecting the lifespan of the model organism. These findings suggest the potential therapeutic effects of metformin on Parkinson's disease, with further investigation needed to determine the precise mechanisms involved.