肌肉萎缩性侧索硬化症相关的致病蛋白TDP43降解机制的研究.pdf

摘要 为了进一步揭示野生型的TDP．43和TDP．25是否通过溶酶体途径降解， 解比TDP．43明显。 通过以上实验，我们得出结论：野生型的TDP．43和病理突变的TDP．25 既能通过泛素蛋白酶体途径降解也能通过溶酶体途径降解，且病理突变的 TDP．25的降解较野生型的TDP．43快。这提示我们能增强这两条通路的药物都 有可能成为其治疗的手段。 关键词：神经退行性疾病TDP．43泛素蛋白酶体降解途径 溶酶体降 解途径 ABSTRACT ABSTRACT diseaseisakindofdisorderwhichiscaused Neurodegenerative by certain deteriorationof neuronsinbrains．Thecommonfeatherofsuchdisorder is formation thatare inoroutsideof aggregate bypathologicalproteins present lateral a disease neurons．Amyotrophicsclerosis(ALS)isneurodegenerative definedthe ofthe motor and classicallyby impairmentvoluntarysystem neuronal inanteriorhorncells．FamilialALS ubiquitin—positiveaggregates isclinically fromthe formofdisease (FALS)that indistinguishabIesporadic hasbeenassociatedwithanumberof lociandmutationsin genetic specific SODlin～20％of increaseofevidence genes，principally cases．Recently，an thatALSiSlinkedtOanother iSfoundinthe shows protein，TDP一43，which inbrainsofALS hasbeenconsideredtobe inclusions patients．TDP一43protein the to are toxicto pathologicalproteinleadingALS．Aggregatesusually major neuronal couldbeof tounderstandthedisease cells．Thus，it help pathology the of towardALS TDP-43． byexploringdegradationpathway Ourres