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The Possible Role of Metformin and Fibroblast Growth Factor-21 in Multiple Sclerosis Neuropathology: Birds of a
Ahmad A Abulaban1,2,3, Hayder M Al-Kuraishy4, Ali I Al-Gareeb4
1College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Abstract:
Multiple sclerosis (MS) is a progressive demyelinating disease of the CNS, characterized by inflammation, the formation of CNS plaques, and damage to the neuronal myelin sheath (Graphical abstract). Fibroblast growth factor 21 (FGF21) is involved in various metabolic disorders and neurodegenerative diseases. FGF21 and its co-receptor β-Kloth are essential in the remyelination process of MS. Metformin, an insulin-sensitizing drug that is the first-line treatment for type 2 diabetes mellitus (T2DM), may have a potential neuroprotective impact by up-regulating the production of FGF21, which may prevent the onset of neurodegenerative diseases including MS. The purpose of this review is to clarify how metformin affects MS neuropathology mechanistically via modifying FGF21. Metformin increases the expression of FGF21. Metformin also increases the expression of β-Klotho, modulates oxidative stress, reduces glutamate-induced excitotoxicity, and regulates platelet function and coagulation cascades. In conclusion, metformin can enhance the functional activity of FGF21 in counteracting the development and progression of MS. Preclinical and clinical studies are warranted in this regard.
Insights
Metformin may protect against multiple sclerosis (MS) by increasing Fibroblast Growth Factor 21 (FGF21). This mechanism could offer a new therapeutic avenue for managing MS neuropathology.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Pharmacology
Background:
- Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating disease characterized by inflammation and myelin sheath damage.
- Fibroblast Growth Factor 21 (FGF21) and its co-receptor β-Klotho play crucial roles in the remyelination process relevant to MS.
- Metformin, a common type 2 diabetes mellitus (T2DM) treatment, is investigated for potential neuroprotective effects.
Purpose of the Study:
- To elucidate the mechanistic pathways through which metformin influences MS neuropathology by modulating FGF21.
- To explore the potential of metformin as a therapeutic agent for MS based on its effects on FGF21.
Main Methods:
- Review of existing literature on metformin, FGF21, β-Klotho, and their roles in MS pathogenesis.
- Analysis of proposed molecular mechanisms linking metformin to FGF21 expression and downstream effects.
Main Results:
- Metformin administration is associated with increased expression of both FGF21 and its co-receptor β-Klotho.
- Metformin demonstrates pleiotropic effects including modulation of oxidative stress, reduction of excitotoxicity, and regulation of coagulation.
Conclusions:
- Metformin enhances the functional activity of FGF21, suggesting a potential therapeutic benefit in counteracting MS development and progression.
- Further preclinical and clinical studies are necessary to validate metformin's efficacy and safety in managing MS.
