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神经干细胞中PFK-1对神经发生的负调控作用.docx

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神经干细胞中PFK-1对神经发生的负调控作用 Title:NegativeRegulatoryRoleofPFK-1inNeurogenesisinNeuralStemCells Abstract: Neurogenesis,theprocessofgeneratingnewneurons,playsacriticalroleinthedevelopmentandmaintenanceofthecentralnervoussystem(CNS).Numerouscellularandmolecularmechanismsregulateneurogenesistoensuretheproperformationandfunctionofthenervoussystem.Inthispaper,wefocusonthenegativeregulatoryroleofPFK-1,akeyenzymeinglycolysis,inneurogenesisinneuralstemcells(NSCs).WediscusstheimportanceofglycolyticmetabolisminNSCs,theinvolvementofPFK-1inneurogenesisregulation,andtheunderlyingmechanismsthroughwhichPFK-1exertsitsnegativeimpactonneurogenesis. 1.Introduction: Neurogenesisisacomplexprocessinvolvingtheproliferation,differentiation,andmaturationofNSCs.Variousintrinsicandextrinsicfactorstightlyregulatethebalancebetweenself-renewalanddifferentiationofNSCs.Recentstudieshavehighlightedtheroleofmetabolicpathwaysintheregulationofneurogenesis.Onesuchpathwayisglycolysis,whichprovidesenergyandmetabolitesessentialfortheproliferationanddifferentiationofNSCs.PFK-1,arate-limitingenzymeinglycolysis,hasemergedasanegativeregulatorofneurogenesis,warrantingfurtherinvestigation. 2.GlycolyticMetabolisminNSCs: NSCsexhibitdistinctmetaboliccharacteristicscomparedtodifferentiatedneuralcells.Glycolysis,theconversionofglucosetopyruvate,isadominantmetabolicpathwayinNSCs.ThispathwaygeneratesATP,providesintermediatesforbiosynthesis,andgeneratesNADHforredoxreactions.PFK-1playsapivotalroleinglycolysisbycatalyzingtheconversionoffructose-6-phosphatetofructose-1,6-bisphosphate.ItsactivityistightlyregulatedandservesasametaboliccheckpointensuringtheavailabilityofenergyandessentialmetabolitesforNSCs. 3.NegativeRegulatoryRoleofPFK-1inNeurogenesis: RecentstudieshaveuncoveredthenegativeimpactofPFK-1onneurogenesis.ModulationofPFK-1activityinfluencescellfatedecisionsinNSCs,leadingtodecreasedneurogenesisandincreasedgliogenesis.PFK-1inhibitionorknockdownenhancesneurogenesis,whileitsoverexpressionsuppressesneuronaldifferentiation.T