Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety,low cost,and outstanding hypoglycemic effect clinically.The mechanisms underlying these benefits are complex and sti...Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety,low cost,and outstanding hypoglycemic effect clinically.The mechanisms underlying these benefits are complex and still not fully understood.Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin,leading to reduced ATP production and activation of AMP-activated protein kinase(AMPK).Meanwhile,many novel targets of metformin have been gradually discovered.In recent years,multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes.Herein,we summarized the benefits of metformin in four types of diseases,including metabolic associated diseases,cancer,aging and age-related diseases,neurological disorders.We comprehensively discussed the pharmacokinetic properties and the mechanisms of action,treatment strategies,the clinical application,the potential risk of metformin in various diseases.This review provides a brief summary of the benefits and concerns of metformin,aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research.Although there have been countless studies of metformin,longitudinal research in each field is still much warranted.展开更多
Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain.Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons.Calretinin(CR)is one of the ...Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain.Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons.Calretinin(CR)is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons.The functions of CR and its role in neural excitability are still unknown.Recent data suggest that CR neurons have diverse neurotransmitters,morphologies,distributions,and functions in different brain regions across various species.Notably,CR neurons in the hippocampus,amygdala,neocortex,and thalamus are extremely susceptible to excitotoxicity in the epileptic brain,but the causal relationship is unknown.In this review,we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy.Importantly,we provide perspectives on future investigations of the role of CR neurons in epilepsy.展开更多
基金founded by China Postdoctoral Science Foundation(No.2021M703345)the National Natural Science Foundation of China(Nos.82130099,81971265,and 81821005)+3 种基金Shanghai Science and Technology Development Funds(Nos.22YF1457100 and 22ZR1415200)National Key R&D Program of China(No.2022YFA1303802)the National Natural Science Foundation of China for Innovation Research Group(No.81821005)the Lingang Laboratory(Nos.LG202103-03-04,LG202103-03-01,and LG202103-03-05).
文摘Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety,low cost,and outstanding hypoglycemic effect clinically.The mechanisms underlying these benefits are complex and still not fully understood.Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin,leading to reduced ATP production and activation of AMP-activated protein kinase(AMPK).Meanwhile,many novel targets of metformin have been gradually discovered.In recent years,multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes.Herein,we summarized the benefits of metformin in four types of diseases,including metabolic associated diseases,cancer,aging and age-related diseases,neurological disorders.We comprehensively discussed the pharmacokinetic properties and the mechanisms of action,treatment strategies,the clinical application,the potential risk of metformin in various diseases.This review provides a brief summary of the benefits and concerns of metformin,aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research.Although there have been countless studies of metformin,longitudinal research in each field is still much warranted.
基金supported by grants from the National Natural Science Foundation of China(8163009&81973298,and 81821091).
文摘Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain.Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons.Calretinin(CR)is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons.The functions of CR and its role in neural excitability are still unknown.Recent data suggest that CR neurons have diverse neurotransmitters,morphologies,distributions,and functions in different brain regions across various species.Notably,CR neurons in the hippocampus,amygdala,neocortex,and thalamus are extremely susceptible to excitotoxicity in the epileptic brain,but the causal relationship is unknown.In this review,we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy.Importantly,we provide perspectives on future investigations of the role of CR neurons in epilepsy.
