:
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 is 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 dissected and the potential therapeutic benefits of metformin administration on the reversal of brain injury in such metabolism dependent diseases will be exposed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.