Buxbaum J D, Choi E K, Luo Y, Lilliehook C, Crowley A C, Merriam D E, Wasco W
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Nat Med. 1998 Oct;4(10):1177-81. doi: 10.1038/2673.
Most early-onset familial Alzheimer disease (AD) cases are caused by mutations in the highly related genes presenilin 1 (PS1) and presenilin 2 (PS2). Presenilin mutations produce increases in beta-amyloid (Abeta) formation and apoptosis in many experimental systems. A cDNA (ALG-3) encoding the last 103 amino acids of PS2 has been identified as a potent inhibitor of apoptosis. Using this PS2 domain in the yeast two-hybrid system, we have identified a neuronal protein that binds calcium and presenilin, which we call calsenilin. Calsenilin interacts with both PS1 and PS2 in cultured cells, and can regulate the levels of a proteolytic product of PS2. Thus, calsenilin may mediate the effects of wild-type and mutant presenilins on apoptosis and on Abeta formation. Further characterization of calsenilin may lead to an understanding of the normal role of the presenilins and of the role of the presenilins in Alzheimer disease.
大多数早发性家族性阿尔茨海默病（AD）病例是由高度相关的基因早老素1（PS1）和早老素2（PS2）的突变引起的。在许多实验系统中，早老素突变会导致β-淀粉样蛋白（Aβ）生成增加和细胞凋亡。一种编码PS2最后103个氨基酸的cDNA（ALG-3）已被鉴定为一种有效的细胞凋亡抑制剂。利用酵母双杂交系统中的这个PS2结构域，我们鉴定出一种与钙和早老素结合的神经元蛋白，我们将其称为钙结合早老素。钙结合早老素在培养细胞中与PS1和PS2都相互作用，并能调节PS2一种蛋白水解产物的水平。因此，钙结合早老素可能介导野生型和突变型早老素对细胞凋亡和Aβ生成的影响。对钙结合早老素的进一步表征可能有助于理解早老素的正常作用以及早老素在阿尔茨海默病中的作用。
