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APOE基因多态性对神经元轴突生长的影响.docx

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APOE基因多态性对神经元轴突生长的影响 Introduction: ThehumanAPOEgeneislocatedonchromosome19q13.2andshowssignificantgeneticandfunctionalpolymorphisms.APOEgeneplaysanessentialroleinlipidtransportandmetabolismandhasbeenassociatedwithvariousneurologicaldisorders,includingAlzheimer'sdisease,traumaticbraininjury,andstroke.Inrecentyears,theroleofAPOEgeneticpolymorphismshasbeenintensivelyinvestigatedinthecontextofnervegrowthandbraindevelopment.SeveralstudieshaveshownthatAPOEgenotypehasasignificantinfluenceonaxongrowthandregenerationinthenervoussystem.Inthispaper,wewilldiscusstheimpactofAPOEgenepolymorphismsonaxongrowthandregenerationinthenervoussystem. APOEgenepolymorphisms: TheAPOEgenehasthreemajorallelicvariants:ε2,ε3,andε4.Thesethreeallelesresultfromtwosinglenucleotidepolymorphisms(SNPs)thatoccuratpositions112and158inthegene'scodingregion.Theε4allelehasbeenlinkedtoanincreasedriskofvariousneurologicaldisorders,includingAlzheimer'sdisease,whiletheε2allelehasbeenshowntohaveaprotectiveeffectagainstAlzheimer'sdisease.Somestudieshavesuggestedthattheε4allelemayalsoinfluencenervegrowthandbraindevelopment. ImpactofAPOEgenepolymorphismsonaxongrowth: SeveralstudieshaveshownthatAPOEgenepolymorphismscanhaveasignificantinfluenceonaxongrowthinthenervoussystem.InastudyconductedwithprimarycorticalneuronsderivedfromAPOEε2,ε3,andε4knock-inmice,itwasfoundthattheε4allelesignificantlyreducedaxonlengthcomparedtotheε2andε3alleles.ThisindicatesthattheAPOEε4allelemayinterferewiththenormalaxongrowthanddevelopmentprocessinthebrain. AnotherstudyconductedintransgenicmiceexpressinghumanAPOEε4showedthatthesemicehadreducedaxondensityinthehippocampuscomparedtomiceexpressingtheε3allele.Thisreducedaxondensitywasalsoassociatedwithalteredsynapticplasticityandimpairedspatialmemoryfunction.ThesefindingssuggestthatAPOEε4allelemayhaveadetrimentaleffectonaxongrowthandsynapticfunctioninthebrain. APOEgenepolymorphismsandaxonregeneration: Inadditiontoitsroleinaxongrowthduringdevelopment,theAPOEgenealsoappearstoplayacriticalroleinaxo