Title:Metformin: A Growing Journey from Glycemic Control to the Treatment of Alzheimer’s Disease and Depression
Volume: 28
Issue: 12
关键词:
代谢应激，二甲双胍，阿尔茨海默病，抑郁症，AMPK通路，胰岛素，葡萄糖转运体
摘要: 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.
