The ameliorative potential of metformin against aluminum-induced neurotoxicity: Insights from in vitro studies


Sanajou S., YİRÜN A., DEMİREL G., ERKEKOĞLU Ü. P., Şahin G., BAYDAR T.

Journal of Applied Toxicology, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2024
  • Doi Number: 10.1002/jat.4695
  • Journal Name: Journal of Applied Toxicology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, Applied Science & Technology Source, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, Communication Abstracts, Environment Index, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Keywords: aluminum, Alzheimer's disease, GSK3-β, metformin, Wnt signaling
  • Çukurova University Affiliated: Yes

Abstract

Alzheimer's disease (AD) is increasingly recognized as a metabolic disorder, often referred to as type 3 diabetes, due to its strong association with insulin resistance. Chronic exposure to aluminum, a known neurotoxin, has been identified as a significant risk factor in the development and progression of AD. This study explores the potential of metformin, a common anti-diabetic drug, to mitigate aluminum-induced neurotoxicity in an in vitro model of AD. Our findings reveal that metformin significantly reduces oxidative stress markers such as malonaldehyde, carbonyl groups, and reactive oxygen species while enhancing antioxidant defenses. Metformin modulates critical signaling pathways, including glycogen synthase kinase 3 beta (GSK3-β)/RAC-alpha serine/threonine protein kinase (RAC-alpha serine/threonine protein kinase (Akt1)/protein phosphatase 2A (PP2A) and Wnt/β-catenin, decreasing Tau protein levels and promoting neurogenesis. These results suggest that metformin may offer a novel therapeutic approach for AD, particularly in cases where aluminum exposure is a contributing factor.