Ironaccumulationandassociatedoxidat

Ironaccumulationandassociatedoxidativestressinthebrainhavebeenconsistentlyfoundinseveralneurodegenerativediseases.Multiplegeneticstudieshavebeenundertakentotrytoidentifyacauseofneurodegenerativediseasesbutdirectconnectionshavebeenrare.Intheironfield,variantsintheHFEgenethatgiverisetoaproteininvolvedincellularironregulation,areassociatedwithironaccumulationinmultipleorgansincludingthebrain.Thereisalsosubstantialepidemiological,genetic,andmolecularevidenceofdisruptionofcholesterolhomeostasisinseveralneurodegenerativediseases,inparticularAlzheimer’sdisease(AD).Despitetheeffortsthathavebeenmadetoidentifyfactorsthatcantriggerthepathologicaleventsassociatedwithneurodegenerativediseasestheremainmostlyunknown.Becausemolecularphenotypessuchasoxidativestress,synapticfailure,neuronalloss,andcognitivedecline,characteristicsassociatedwithAD,havebeenshowntoresultfromdisruptionofanumberofpathways,onecaneasilyarguethatthephenotypeseenmaynotarisefromalinearsequenceofevents.Therefore,amulti-targetedapproachisneededtounderstandacomplexdisorderlikeAD.Thiscanbeachievedonlywhenknowledgeaboutinteractionsbetweenthedifferentpathwaysandthepotentialinfluenceofenvironmentalfactorsontembecomesavailable.Towardthisend,thisreviewdiscusseswhatisknownabouttherolesandinteractionsofironandcholesterolinneurodegenerativediseases.IthighlightstheeffectsofgenevariantsofHFE(H63D-andC282Y-HFE)onironandcholesterolmetabolismandhowtheymaycontributetounderstandingtheetiologyofcomplexneurodegenerativediseases.

ผลลัพธ์ (ไทย) 3:

ironaccumulationandassociatedoxidativestressinthebrainhavebeenconsistentlyfoundinseveralneurodegenerativediseases . multiplegeneticstudieshavebeenundertakentotrytoidentifyacauseofneurodegenerativediseasesbutdirectconnectionshavebeenrare . intheironfield variantsinthehfegenethatgiverisetoaproteininvolvedincellularironregulation areassociatedwithironaccumulationinmultipleorgansincludingthebrain , , .thereisalsosubstantialepidemiological พันธุกรรม andmolecularevidenceofdisruptionofcholesterolhomeostasisinseveralneurodegenerativediseases inparticularalzheimer'sdisease , ( โฆษณา ) despitetheeffortsthathavebeenmadetoidentifyfactorsthatcantriggerthepathologicaleventsassociatedwithneurodegenerativediseasestheremainmostlyunknown . becausemolecularphenotypessuchasoxidativestress synapticfailure neuronalloss , , ,andcognitivedecline,characteristicsassociatedwithAD,havebeenshowntoresultfromdisruptionofanumberofpathways,onecaneasilyarguethatthephenotypeseenmaynotarisefromalinearsequenceofevents.Therefore,amulti-targetedapproachisneededtounderstandacomplexdisorderlikeAD.Thiscanbeachievedonlywhenknowledgeaboutinteractionsbetweenthedifferentpathwaysandthepotentialinfluenceofenvironmentalfactorsontembecomesavailable.Towardthisend,thisreviewdiscusseswhatisknownabouttherolesandinteractionsofironandcholesterolinneurodegenerativediseases.IthighlightstheeffectsofgenevariantsofHFE(H63D-andC282Y-HFE)onironandcholesterolmetabolismandhowtheymaycontributetounderstandingtheetiologyofcomplexneurodegenerativediseases.