Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzhe...Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.展开更多
目的:观察中等强度持续运动(MICT)与高强度间歇运动(HIIT)对高脂膳食大鼠心肌和比目鱼肌超微结构的影响并探讨其机制。方法:5周龄雄性SD大鼠随机分为普通膳食安静组(C)、高脂膳食安静组(F)、高脂膳食MICT组(M)和高脂膳食HIIT组(H),每组8...目的:观察中等强度持续运动(MICT)与高强度间歇运动(HIIT)对高脂膳食大鼠心肌和比目鱼肌超微结构的影响并探讨其机制。方法:5周龄雄性SD大鼠随机分为普通膳食安静组(C)、高脂膳食安静组(F)、高脂膳食MICT组(M)和高脂膳食HIIT组(H),每组8只,高脂膳食饲料脂肪含量为45%。M和H组进行12周坡度为25°的跑台运动,M组进行70%VO_(2)max强度的持续运动,H组进行以5 min 40%~45%VO_(2)max和4 min 95%~99%VO_(2)max强度依次交替的间歇运动。干预结束后检测血清FFA、TG、HDL、LDL含量;透射电镜观察大鼠心肌和比目鱼肌超微结构;Western blot检测心肌和比目鱼肌AMPK、MCD及CPT-1的蛋白表达。结果:与C组比较,F组大鼠体重、Lee`s指数、血清LDL、TG和FFA含量均增加,HDL含量降低(P<0.05);心肌和比目鱼肌AMPK、CPT-1蛋白表达升高,MCD蛋白表达降低(P<0.05),超微结构损伤。与F组比较,M、H组大鼠体重、Lee`s指数降低、血清LDL、FFA含量降低(P<0.01);心肌AMPK、MCD、CPT-1蛋白表达增加,比目鱼肌AMPK、MCD蛋白表达增加(P<0.05),超微结构损伤减轻。与M组比较,H组大鼠血清HDL含量增加(P<0.01),心肌AMPK、MCD蛋白表达增加,超微结构损伤较轻;比目鱼肌AMPK蛋白表达降低,MCD蛋白表达增加(P<0.05),超微结构损伤较重。结论:MICT与HIIT可通过干预AMPK、MCD、CPT-1蛋白表达,对高脂膳食大鼠心肌和比目鱼肌超微结构产生不同影响。展开更多
瘦蛋白(leptin)介导的腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)信号转导途径在脂肪代谢的调节中起重要作用。瘦蛋白与其受体结合使AMPK信号转导途径激活,最终激活肉碱脂酰转移酶-1,通过促进脂肪酸氧化而参与脂肪代谢的...瘦蛋白(leptin)介导的腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)信号转导途径在脂肪代谢的调节中起重要作用。瘦蛋白与其受体结合使AMPK信号转导途径激活,最终激活肉碱脂酰转移酶-1,通过促进脂肪酸氧化而参与脂肪代谢的调节。本文主要介绍近年来关于瘦蛋白介导的AMPK信号转导途径的组成、活性调节及其作用机制的最新研究进展。展开更多
文摘Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.
文摘目的:观察中等强度持续运动(MICT)与高强度间歇运动(HIIT)对高脂膳食大鼠心肌和比目鱼肌超微结构的影响并探讨其机制。方法:5周龄雄性SD大鼠随机分为普通膳食安静组(C)、高脂膳食安静组(F)、高脂膳食MICT组(M)和高脂膳食HIIT组(H),每组8只,高脂膳食饲料脂肪含量为45%。M和H组进行12周坡度为25°的跑台运动,M组进行70%VO_(2)max强度的持续运动,H组进行以5 min 40%~45%VO_(2)max和4 min 95%~99%VO_(2)max强度依次交替的间歇运动。干预结束后检测血清FFA、TG、HDL、LDL含量;透射电镜观察大鼠心肌和比目鱼肌超微结构;Western blot检测心肌和比目鱼肌AMPK、MCD及CPT-1的蛋白表达。结果:与C组比较,F组大鼠体重、Lee`s指数、血清LDL、TG和FFA含量均增加,HDL含量降低(P<0.05);心肌和比目鱼肌AMPK、CPT-1蛋白表达升高,MCD蛋白表达降低(P<0.05),超微结构损伤。与F组比较,M、H组大鼠体重、Lee`s指数降低、血清LDL、FFA含量降低(P<0.01);心肌AMPK、MCD、CPT-1蛋白表达增加,比目鱼肌AMPK、MCD蛋白表达增加(P<0.05),超微结构损伤减轻。与M组比较,H组大鼠血清HDL含量增加(P<0.01),心肌AMPK、MCD蛋白表达增加,超微结构损伤较轻;比目鱼肌AMPK蛋白表达降低,MCD蛋白表达增加(P<0.05),超微结构损伤较重。结论:MICT与HIIT可通过干预AMPK、MCD、CPT-1蛋白表达,对高脂膳食大鼠心肌和比目鱼肌超微结构产生不同影响。
文摘瘦蛋白(leptin)介导的腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)信号转导途径在脂肪代谢的调节中起重要作用。瘦蛋白与其受体结合使AMPK信号转导途径激活,最终激活肉碱脂酰转移酶-1,通过促进脂肪酸氧化而参与脂肪代谢的调节。本文主要介绍近年来关于瘦蛋白介导的AMPK信号转导途径的组成、活性调节及其作用机制的最新研究进展。
