CAJ | 학술논문

阿尔茨海默病( Alzheimer′s disease,AD)是一种神经退行性疾病。根据近年来的研究,AD的可能致病因素主要是由tau、APP以及 Aβ引起神经元退化以及神经细胞凋亡。tau经caspases切割后会发生聚集,进而发生神经纤维缠结使神经元退化及死亡。细胞凋亡途径都需要caspases的活化,并且是凋亡的启动者、执行者。 APP经β-、γ-分泌酶作用产生sAPPβ、Aβ40/42,其中Aβ42经DR4/5激活下游凋亡信号以及经 caspase 切割形成的 C31片段,可促进细胞凋亡。sAPPβ水解后产生的N-APP可经DR6促进神经元的异常发展,但水解位点及机制并不清楚。其中,caspase可以通过作用于γ-分泌酶激活蛋白调节Aβ40/42以及C31的生成,进而影响AD的发生。目前关于AD的治疗还没有针对caspase的药物。在这篇综述中,我们就神经细胞凋亡机制及其通路中caspases在AD发生过程中的相关作用进行阐明,为药物研发以及临床治疗提供一些可能的治疗靶点。
아이자해묵병( Alzheimer′s disease,AD)시일충신경퇴행성질병。근거근년래적연구,AD적가능치병인소주요시유tau、APP이급 Aβ인기신경원퇴화이급신경세포조망。tau경caspases절할후회발생취집,진이발생신경섬유전결사신경원퇴화급사망。세포조망도경도수요caspases적활화,병차시조망적계동자、집행자。 APP경β-、γ-분비매작용산생sAPPβ、Aβ40/42,기중Aβ42경DR4/5격활하유조망신호이급경 caspase 절할형성적 C31편단,가촉진세포조망。sAPPβ수해후산생적N-APP가경DR6촉진신경원적이상발전,단수해위점급궤제병불청초。기중,caspase가이통과작용우γ-분비매격활단백조절Aβ40/42이급C31적생성,진이영향AD적발생。목전관우AD적치료환몰유침대caspase적약물。재저편종술중,아문취신경세포조망궤제급기통로중caspases재AD발생과정중적상관작용진행천명,위약물연발이급림상치료제공일사가능적치료파점。
Alzheimer′s disease ( AD) is a type of neurodegener-ative disease. Recent studies indicate that neuronal degeneration and loss triggered by tau, APP and Aβare the probable risks for AD. Neurofibrillary tangles are formed after tau truncated by ac-tivated caspases and subsequently induced tau aggregates, which causes neuronal degeneration and loss. In addition, caspases are crucial components in the biological functioning in the apoptosis pathways. Apoptosis pathway involves activation of upstream ini-tiator caspase-8 and downstream executor caspase-3/-6/-7. After the actions of β- and γ-secretase, APP transforms into sAPPβand Aβ40/42 . Aggregated Aβ42 can activate apoptosis pathway through DR4/5 interaction. C-APP is truncated into C31 frag-ments by caspases and cell apoptosis is facilitated. N-APP, a product of sAPPβhydrolysis, can promote the abnormal develop-ment of neurons mediated by DR6. Caspase activates γ-secre-tase-activating protein to regulate activity ofγ-secretase, and the production of C31 and Aβ40/42 , which, then, causes the occur-rence of AD. This brief review summarizes the specific roles of caspases and the concerning apoptosis pathways on the mecha-nisms of neuronal degeneration and loss, and how they impact the occurrence of AD in the hope of uncovering additional poten-tial therapeutic targets that can be employed in drug development and clinical therapy for AD.