中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
1期
11-14
,共4页
雷帕霉素%雷帕霉素靶蛋白%自噬%早老症%早老蛋白%神经退行性疾病
雷帕黴素%雷帕黴素靶蛋白%自噬%早老癥%早老蛋白%神經退行性疾病
뢰파매소%뢰파매소파단백%자서%조로증%조로단백%신경퇴행성질병
rapamycin%TOR%autophagy%HGPS%progerin%neurodegenerative diseases
哺乳动物雷帕霉素靶蛋白( mammalian target of rapamy-cin, mTOR)是衰老和衰老相关疾病的一个关键调节因子。雷帕霉素( rapamycin, RAPA)可通过抑制mTOR通路,诱导和促进细胞自噬的发生。细胞自噬是维持细胞内稳态的主要方式与途径,通过降解多余的、受损的及衰老的蛋白与细胞器,为细胞重建、再生和修复提供必需原料。早老症( hutchinson-gil-ford progeria syndrome, HGPS )患者细胞中伴随早老蛋白( progerin)的异常聚集；此外,诸如亨廷顿病、帕金森病、阿尔茨海默病等神经退行性疾病细胞内同样出现异常蛋白质的聚集,而这些异常蛋白的清除正依赖于细胞的自噬作用。由此可见,雷帕霉素是潜在的抗衰老、治疗早老症及衰老相关疾病的重要药物。该文主要阐述雷帕霉素促进细胞自噬方面的功能及在HGPS、神经退行性疾病方面的应用。
哺乳動物雷帕黴素靶蛋白( mammalian target of rapamy-cin, mTOR)是衰老和衰老相關疾病的一箇關鍵調節因子。雷帕黴素( rapamycin, RAPA)可通過抑製mTOR通路,誘導和促進細胞自噬的髮生。細胞自噬是維持細胞內穩態的主要方式與途徑,通過降解多餘的、受損的及衰老的蛋白與細胞器,為細胞重建、再生和脩複提供必需原料。早老癥( hutchinson-gil-ford progeria syndrome, HGPS )患者細胞中伴隨早老蛋白( progerin)的異常聚集；此外,諸如亨廷頓病、帕金森病、阿爾茨海默病等神經退行性疾病細胞內同樣齣現異常蛋白質的聚集,而這些異常蛋白的清除正依賴于細胞的自噬作用。由此可見,雷帕黴素是潛在的抗衰老、治療早老癥及衰老相關疾病的重要藥物。該文主要闡述雷帕黴素促進細胞自噬方麵的功能及在HGPS、神經退行性疾病方麵的應用。
포유동물뢰파매소파단백( mammalian target of rapamy-cin, mTOR)시쇠로화쇠로상관질병적일개관건조절인자。뢰파매소( rapamycin, RAPA)가통과억제mTOR통로,유도화촉진세포자서적발생。세포자서시유지세포내은태적주요방식여도경,통과강해다여적、수손적급쇠로적단백여세포기,위세포중건、재생화수복제공필수원료。조로증( hutchinson-gil-ford progeria syndrome, HGPS )환자세포중반수조로단백( progerin)적이상취집；차외,제여형정돈병、파금삼병、아이자해묵병등신경퇴행성질병세포내동양출현이상단백질적취집,이저사이상단백적청제정의뢰우세포적자서작용。유차가견,뢰파매소시잠재적항쇠로、치료조로증급쇠로상관질병적중요약물。해문주요천술뢰파매소촉진세포자서방면적공능급재HGPS、신경퇴행성질병방면적응용。
Mammalian target of rapamycin( mTOR) is a key reg-ulator of aging and aging-related diseases. Rapamycin ( RAPA) induces and promotes the process of cell autophagy through in-hibiting mTOR pathway. Autophagy exerts a crucial role in main-taining the cellular meostasis, which provides essential materials for cell reconstruction, regeneration and repair via degradating the redundant, damaged, or senescent proteins and organelles. Hutchinson Gilford progeria syndrome ( HGPS ) patients are al-ways accompanied with abnormally accumulated progerin in cells. Similar to HGPS, abnormal protein accumulation is the common pathological feature of neurodegenerative diseases, in-cluding Huntington′s disease, Parkinson′s disease, Alzheimer′s disease and so on. Degradation of these abnormal proteins pre-dominantly depends on cell autophagy. Thus, rapamycin is a po-tential anti-aging drug for HGPS and aging-related diseases thera-py. This view focuses on the effects of rapamycin on cell autoph-agy and clinical application in HGPS and neurodegenerative dis-eases.
