Kinesin‐1 inhibits the aggregation of amyloid‐β peptide as detected by fluorescence cross‐correlation spectroscopy

摘要

AlthoughtheexactetiologyandpathogenesisofAlzheimer'sdisease(AD)arestillunclear,amyloid‐β(Aβ)generatedbytheproteolyticprocessingofamyloid‐βprecursorprotein(APP)aggregatetoformtoxicamyloidspecies.Kinesin‐1isthefirstidentifiedATP‐dependentaxonaltransportmotorproteinthathasbeenproventoaffectAβgenerationanddeposition.Inthispaper,weapplieddual‐colorfluorescencecross‐correlationspectroscopy(DC‐FCCS)toinvestigatethedirectinteractionofAβwithkinesin‐1atthesingle‐moleculefluorescencelevelinvitro.Theresultsshowedthattwokindsofenhancedgreenfluorescentprotein(EGFP)‐taggedkinesinlight‐chainsubunitsofkinesin‐1(KLCs),KLC‐EandE‐KLCinhibitedtheaggregationofAβoveraperiodoftime,providingadditionalinsightintothemechanismofaxonaltransportdeficitsinAD...