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                清華大學施一公研究組揭示老年癡呆癥“罪魁禍首
                來源: | 作者: | 發布時間:2013-9-25 9:31:49


                       在預防和治療老年癡呆癥(學名阿爾茨海默癥)上,醫學界一直缺乏特效藥物。清華大學施一公研究組在世界上首次揭示了老年癡呆癥“罪魁禍首”——人源γ分泌酶復合物(γ-secretase)的精細三維結構,為理解γ分泌酶復合物的工作機制以及阿爾茨海默癥的發病機理提供了重要線索。該成果由英國《自然》雜志6月29日在線發表。


                7月3日,施一公在清華召開的發布會上展示了這項成果:分辨率達到4.5埃的γ-secretase三維結構,讓人類第一次看到了其真實形狀、組成和幾乎所有的蛋白質二級結構(α-螺旋和β-折疊)。該結構顯示,γ-secretase膜內部分呈馬蹄型,全部19個跨膜螺旋清晰可辨。

                阿爾茨海默癥患者表現為認知和記憶能力受損,大腦功能逐漸喪失直至死亡。我國目前大約有500萬阿爾茨海默癥患者,占世界發病總數的四分之一。

                施一公告訴記者,γ-secretase相當于人體的“垃圾粉碎機”,主要作用是切割細胞膜上的一些廢物蛋白,把它們分解成小的片段,讓人體再吸收、利用。γ-secretase由四個亞基構成,其中起重要作用的是早老素Presenilin活性亞基。當它發生異常時,γ-secretase在切割蛋白時就會產生過量的Aβ42肽段。這些“堆積在一起的Aβ42肽段,會形成淀粉樣的沉淀,引起腦細胞凋亡,讓人失去記憶。”施一公說。在阿爾茨海默癥患者腦內,發現了大量的Aβ42肽段。

                他們今后將進一步提高γ-secretase的分辨率,捕捉其完整工作過程。“我們做的都是基礎研究,將來可以根據這個結構設計靶向分子藥物,這是一種愿景吧!”施一公表示。

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