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Review
. 2025 Jun 9.
doi: 10.1007/s12035-025-05126-7. Online ahead of print.

The AMPK/GDF15 Axis: A Novel Target for the Neuroprotective Effects of Metformin in Ischemic Stroke

Ghadah H Alshehri  1 , Hayder M Al-Kuraishy  2 , Bshra A Alsfouk  3 , Ali I Al-Gareeb  2 , Safaa A Faheem  4 , Athanasios Alexiou  5   6 , Marios Papadakis  7 , Gaber El-Saber Batiha  8
Affiliations
Review

The AMPK/GDF15 Axis: A Novel Target for the Neuroprotective Effects of Metformin in Ischemic Stroke

Ghadah H Alshehri et al. Mol Neurobiol. .

Abstract

Metformin is an anti-diabetic drug used in the management of type 2 diabetes (T2D). Metformin has different pleiotropic effects, such as anti-inflammatory, antioxidant, antithrombotic, and vasculoprotective. Metformin has neuroprotective effects against neurodegenerative diseases and ischemic stroke. Conversely, metformin may exacerbate the pathogenesis of ischemic stroke. This controversial point may be related to the impact of metformin on the different signaling pathways, such as AMP-activated protein kinase (AMPK) and growth differentiation factor 15 (GDF-15). Many studies have reported the effect of metformin on ischemic stroke, with AMPK signaling only. However, little has been explored about the impact of metformin on the GDF-15 signaling in ischemic stroke. Accordingly, this review aims to discuss the role of metformin in the neuropathology of ischemic stroke regarding the AMPK and GDF-15 signaling pathways.

Keywords: AMP-activated protein kinase; Growth differentiation factor 15; Ischemic stroke; Metformin.

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Conflict of interest statement

Declarations. Ethics Approval and Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing interests: The authors declare no competing interests.

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