Wolozin B, Iwasaki K, Vito P, Ganjei J K, Lacanà E, Sunderland T, Zhao B, Kusiak J W, Wasco W, D'Adamio L
Unit on Alzheimer Biology, Laboratory of Clinical Science, National Institute of Mental Health, Building 10, Room 3D41, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Science. 1996 Dec 6;274(5293):1710-3. doi: 10.1126/science.274.5293.1710.
Overexpression of the familial Alzheimer's disease gene Presenilin 2 (PS2) in nerve growth factor-differentiated PC12 cells increased apoptosis induced by trophic factor withdrawal or beta-amyloid. Transfection of antisense PS2 conferred protection against apoptosis induced by trophic withdrawal in nerve growth factor-differentiated or amyloid precursor protein-expressing PC12 cells. The apoptotic cell death induced by PS2 protein was sensitive to pertussis toxin, suggesting that heterotrimeric GTP-binding proteins are involved. A PS2 mutation associated with familial Alzheimer's disease was found to generate a molecule with enhanced basal apoptotic activity. This gain of function might accelerate the process of neurodegeneration that occurs in Alzheimer's disease, leading to the earlier age of onset characteristic of familial Alzheimer's disease.
家族性阿尔茨海默病基因早老素2（PS2）在神经生长因子分化的PC12细胞中的过表达增加了因营养因子撤除或β-淀粉样蛋白诱导的细胞凋亡。反义PS2的转染赋予了在神经生长因子分化的或表达淀粉样前体蛋白的PC12细胞中对抗因营养因子撤除诱导的细胞凋亡的保护作用。PS2蛋白诱导的凋亡性细胞死亡对百日咳毒素敏感，提示异三聚体GTP结合蛋白参与其中。发现一个与家族性阿尔茨海默病相关的PS2突变产生了具有增强的基础凋亡活性的分子。这种功能获得可能加速阿尔茨海默病中发生的神经退行性变过程，导致家族性阿尔茨海默病特征性的发病年龄提前。
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