HDAC6 Inhibitor Blocks Amyloid Beta-Induced Impairment of Mitochondrial Transport in Hippocampal Neurons 英文参考文献.docVIP

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HDAC6 Inhibitor Blocks Amyloid Beta-Induced Impairment of Mitochondrial Transport in Hippocampal Neurons 英文参考文献.doc

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HDAC6 Inhibitor Blocks Amyloid Beta-Induced Impairment of Mitochondrial Transport in Hippocampal Neurons 英文参考文献

HDAC6InhibitorBlocksAmyloidBeta-Induced ImpairmentofMitochondrialTransportinHippocampal Neurons ChaeyoungKim1.,HeesunChoi1.,EunSunJung1,WonikLee1,SoojungOh2,3,NooLiJeon2,3 , InheeMook-Jung1* 1DepartmentofBiochemistryandBiomedicalSciences,SeoulNationalUniversityCollegeofMedicine,Seoul,Korea,2SchoolofMechanicalandAerospaceEngineering, SeoulNationalUniversity,Seoul,Korea,3WorldClassUniversity(WCU)ProgramofMultiscaleDesign,SchoolofMechanicalandAerospaceEngineering,SeoulNational University,Seoul,Korea Abstract Eventhoughthedisruptionof axonaltransport isanimportant pathophysiological factor inneurodegenerative diseases including Alzheimer’s disease (AD), the relationship between disruption of axonal transport and pathogenesis of AD is poorlyunderstood.Consideringthata-tubulinacetylationisanimportantfactorinaxonaltransportandthatAbimpairs mitochondrialaxonaltransport,wemanipulatedthelevelofa-tubulinacetylationinhippocampalneuronswithAbcultured in a microfluidic system and examined its effect on mitochondrial axonal transport. We found that inhibiting histone deacetylase6(HDAC6),whichdeacetylatesa-tubulin,significantlyrestoredthevelocityandmotilityofthemitochondriain both anterograde and retrograde axonal transports, which would be otherwise compromised by Ab. The inhibition of HDAC6 also recovered the length of the mitochondria that had been shortened by Ab to a normal level. These results suggest that the inhibition of HDAC6 significantly rescues hippocampal neurons from Ab-induced impairment of mitochondrialaxonaltransportaswellasmitochondriallength.TheresultspresentedinthispaperidentifyHDAC6asan importantregulatorofmitochondrialtransportaswellaselongationand,thus,apotentialtargetwhosepharmacological inhibitioncontributestoimprovingmitochondrialdynamicsinAbtreatedneurons. Citation:KimC,ChoiH,JungES,LeeW,OhS,etal.(2012)HDAC6InhibitorBlocksAmyloidBeta-InducedImpairmentofMitochondrialTransportinHippocampal Neurons.PLoSONE7(8):e42983.doi:10.1371/journal.pone.0042983 Ed