Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signalin...Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Background Lactate dehydrogenase （LDH） is a crucial regulator of energy metabolism in many organs including the heart. Lovastatin is widely used in prevention and treatment of coronary heart disease and is a drug wi...Background Lactate dehydrogenase （LDH） is a crucial regulator of energy metabolism in many organs including the heart. Lovastatin is widely used in prevention and treatment of coronary heart disease and is a drug with substantial metabolic influences. Our study aimed to determine the activities of the lactate dehydrogenase A and B （LDHA and LDHB）genes following lovastatin treatment.Methods The rat myocardial cell line H9c2（2-1） in culture was exposed to 100 nmol/L lovastatin for 24 hours or for five days. The functions of the LDHA and LDHB genes were examined at the transcriptional （mRNA） level with quantitative real-time polymerase chain reaction （Q-RT-PCR）, and at the translational （protein） level with immunoblotting.Results When compared with control levels, the LDHA mRNA went up by （151.65±16.72）% （P=0.0132） after 24 hours and by （175.28±56.54）% （P=0.0366） after five days of lovastatin treatment. Although 24 hours of lovastatin treatment had no significant effects on LDHB mRNA levels, when the treatment was extended to five days, LDHB mRNA levels were significantly down-regulated to （63.65±15.21）% of control levels （P=0.0117）. After 24 hours of treatment with lovastatin,there were no significant changes in protein levels of either LDHA or LDHB. When treatment time was extended to five days, the protein levels of LDHA were up-regulated by （148.65±11.81）% （P=0.00969）, while the protein levels of LDHB were down-regulated to （64.91±5.47）% of control levels （P=0.0192）.Conclusions Lovastatin affects gene activities of LDHA and LDHB differently, which may reveal novel pharmacological effects of lovastatin.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82230042 and 81930029(to ZY),U2004201(to FG and RYP)the China Postdoctoral Science Foundation,No.2020M683748(to RYP)。
文摘Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by grants from the National Natural Science Foundation of China(No.31040011,31260512 and 30960054)the Key Science and Technology Project of Ministry of Education,China(No.209132)
文摘Background Lactate dehydrogenase （LDH） is a crucial regulator of energy metabolism in many organs including the heart. Lovastatin is widely used in prevention and treatment of coronary heart disease and is a drug with substantial metabolic influences. Our study aimed to determine the activities of the lactate dehydrogenase A and B （LDHA and LDHB）genes following lovastatin treatment.Methods The rat myocardial cell line H9c2（2-1） in culture was exposed to 100 nmol/L lovastatin for 24 hours or for five days. The functions of the LDHA and LDHB genes were examined at the transcriptional （mRNA） level with quantitative real-time polymerase chain reaction （Q-RT-PCR）, and at the translational （protein） level with immunoblotting.Results When compared with control levels, the LDHA mRNA went up by （151.65±16.72）% （P=0.0132） after 24 hours and by （175.28±56.54）% （P=0.0366） after five days of lovastatin treatment. Although 24 hours of lovastatin treatment had no significant effects on LDHB mRNA levels, when the treatment was extended to five days, LDHB mRNA levels were significantly down-regulated to （63.65±15.21）% of control levels （P=0.0117）. After 24 hours of treatment with lovastatin,there were no significant changes in protein levels of either LDHA or LDHB. When treatment time was extended to five days, the protein levels of LDHA were up-regulated by （148.65±11.81）% （P=0.00969）, while the protein levels of LDHB were down-regulated to （64.91±5.47）% of control levels （P=0.0192）.Conclusions Lovastatin affects gene activities of LDHA and LDHB differently, which may reveal novel pharmacological effects of lovastatin.
