Cited by 27Metabolism, Diabetes, and CancerAlzheimer's disease research and treatmentsNeurological Disorders and Treatments

Metformin: A Growing Journey from Glycemic Control to the Treatment of Alzheimer’s Disease and Depression

El Massry, Mohamed, Alaeddine, Lynn M., Ali, Leen, Saad, Celine, Eid, Assaad A.·2021·Current Medicinal Chemistry

Abstract

Metabolic stress, transduced as an altered cellular redox and energy status, presents as the main culprit in many diseases, including diabetes. However, its role in the pathology of neurological disorders is still not fully elucidated. Metformin, a biguanide compound, is an FDA approved antidiabetic drug generally used for the treatment of type 2 diabetes. The recently described wide spectrum of action executed by this drug suggests a potential therapeutic benefit in a panoply of disorders. Current studies imply that metformin could play a neuroprotective role by reversing hallmarks of brain injury (metabolic dysfunction, neuronal dystrophy and cellular loss), in addition to cognitive and behavioral alterations that accompany the onset of certain brain diseases such as Alzheimer’s disease (AD) and depression. However, the mechanisms by which metformin exerts its protective effect in neurodegenerative disorders are not yet fully elucidated. The aim of this review is to reexamine the mechanisms through which metformin performs its function while concentrating on its effect on reestablishing homeostasis in a metabolically disturbed milieu. We will also highlight the importance of metabolic stress, not only as a component of many neurological disorders, but also as a primary driving force for neural insult. Of interest, we will explore the involvement of metabolic stress in the pathobiology of AD and depression. The derangement in major metabolic pathways, including AMPK, insulin and glucose transporters, will be explored and the potential therapeutic effects of metformin administration on the reversal of brain injury in such metabolism dependent diseases will be exposed.

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Registry

Crossref · 10.2174/0929867327666200908114902

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160 of 160 references verified0 citation errors · 0 not checkable

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Authors
El Massry, M., Alaeddine, L. M., Ali, L., Saad, C., & Eid, A. A.
Affiliations
  • Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Bliss Street, 11-0236, Riad El-Solh 1107-2020, Beirut,Lebanon
  • American University of Beirut Medical Center (LB)
Corresponding author
Eid, Assaad A.
Venue
Current Medicinal Chemistry
Published
2021-04
Volume
28
Issue
12
Pages
2328-2345
ISSN
0929-8673 (ISSN-L)
OpenAlex
W3084274097
Cited by
27
References
160
Citations by year
2025: 2 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 5
FWCI
0.45
Type
journal article
Language
en
Open access
closed
Locations
  • Current Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords
metformin, Alzheimer's disease, depression, metabolic stress, neuroprotection, AMPK signaling, insulin signaling, glucose transporters, type 2 diabetes, glycemic control, redox state, energy metabolism, neurodegeneration
MeSH terms
Glycemic Control, Alzheimer Disease, Depression, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Metformin

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