《nhe regulation and deregulation of Wnt signaling by PARK genes in health and disease.》.pdf
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《nhe regulation and deregulation of Wnt signaling by PARK genes in health and disease.》.pdf
doi:lO.1O93/jmcb/mjtO37 JoumalofMolecularCellBiology(2014),6,3-12 J3
PublishedonlineOctober9,2013
Review
Theregulati
onandderegulationofWntsignaling
byPARKgenesinhealthanddisease
DanielC.BerwickandKirstenHarvey
DepartmentofPharmacology,UCLSchoolofPharmacy。UniversityCollegeLondon, 29-39BrunswickSquare,LondonWCINlAX,UK
Correspondenceto:KirstenHarvey。E-mail:kirsten.harvey@uc1.ac.uk
WingIess/Int(Wnt)signalingpathwaysaresignaItransductionmechanismsthathavebeenwidelystudiedjnthefieldofembryogen.
esis.RecentworkhasestablishedacriticaIroleforthesepathwaysinbraindevelopment。especiallyofmidbraindopaminergicneu.
rones.However。thefundamentalimportanceofWntsignalingforthenormaIfunctionofmatureneuronesIntheadultcentraI
nervoussystemhasalsolatelybeendemonstratedbyanincreasingnumberofstudies.Parkinson’sdisease(PD)isthesecondmost
prevalentneurodegenerativediseaseworldwideandiscurrentlyfncurab[e.Thisdebilitatingdiseaseischaracterizedbytheprogres-
siveIOSSofasubsetofmidbraindopaminergicneumnesinthesubstont/o,, r口leadingtotypica[extrapyramidaImotorsymptoms.The
aetiologyOfPDispoorlyunderstoodbutworkperformedovertheIasttwodecadeshasIdent[fledagrowingnumberofgeneticdefects
thatunderiiethiscondition.HerewereviewagrowingbodyofdataconnectinggenesimplicatedInPD--mostnotablythePARKgenes--
withWntsignaling.TheseobservationsprovidecluestothenormaIfunctionoftheseproteinsinhealthyneuronesandsuggestthat
deregulatedWntsignalingmightbeafrequentpathOmechanIsm IeadingtoPD.Theseobservationshaveimplicationsufrthepatho-
genesisandtreatmentofneurode-generativediseasesingenera[.
Keywords:Wntsignaling,neurodegeneratiOn,Parkinson’sdisease,geneticsofParkinson’sdisease,LRRK2,treatment
Introduction Iargeburdenonheatthcaresystemsinyearstocome.Assuch。
Parkinson’sdisease(PD)isaprogressiveneurodegenerative thedevelopmentofnoveItreatmentsforPD—m
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