摘要
Parkinsonsdisease(PD)isacommon,progressiveneurodegenerativediseasecharacterisedbydegenerationofnigrostriataldopaminergicneurons,aggregationofα-synucleinandmotorsymptoms.Currentdopamine-replacementstrategiesprovidesymptomaticrelief,howevertheireffectivenesswearoffovertimeandtheirprolongeduseleadstodisablingside-effectsinPDpatients.ThereisthereforeacriticalneedtodevelopnewdrugsanddrugtargetstoprotectdopaminergicneuronsandtheiraxonsfromdegenerationinPD.Overrecentyears,therehasbeenrobustevidencegeneratedshowingthatepigeneticdysregulationoccursinPDpatients,andthatepigeneticmodulationisapromisingtherapeuticapproachforPD.Thisarticlefirstdiscussesthepresentevidenceimplicatingglobal,anddopaminergicneuron-specific,alterationsinthemethylomeinPD,andthetherapeuticpotentialofpharmacologicallytargetingthemethylome.Itthenfocusesonanothermechanismofepigeneticregulation,histoneacetylation,anddescribeshowthehistoneacetyltransferase(HAT)andhistonedeacetylase(HDAC)enzymesthatmediatethisprocessareattractivetherapeutictargetsforPD.Itdiscussestheuseofactivatorsand/orinhibitorsofHDACsandHATsinmodelsofPD,andhowtheseapproachesfortheselectivemodulationofhistoneacetylationelicitneuroprotectiveeffects.Finally,itoutlinesthepotentialofemployingsmallmoleculeepigeneticmodulatorsasneuroprotectivetherapiesforPD,andthefutureresearchthatwillberequiredtodetermineandrealisethistherapeuticpotential.
出版日期
2016年11月21日（中国期刊网平台首次上网日期，不代表论文的发表时间）
