Cowburn Richard F, Popescu Bogdan O, Ankarcrona Maria, Dehvari Nodi, Cedazo-Minguez Angel
Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, KI-Alzheimer's Disease Research Center, Novum, plan 5, S-141 57 Huddinge, Sweden.
Physiol Behav. 2007 Sep 10;92(1-2):93-7. doi: 10.1016/j.physbeh.2007.05.053. Epub 2007 May 25.
Presenilin proteins, mutated forms of which cause early onset familial Alzheimer's disease, are capable of modulating various cell signal transduction pathways, the most extensively studied of which has been intracellular calcium signalling. Disease causing presenilin mutations can potentiate inositol(1,4,5)trisphosphate (InsP3) mediated endoplasmic reticulum release due to calcium overload in this organelle, as well as attenuate capacitative calcium entry. Our own studies have shown a novel function for presenilins that involves regulation of acetylcholine muscarinic receptor-stimulated phospholipase C upstream of InsP3 regulated calcium release. This article reviews the mechanisms by which presenilins modulate intracellular calcium signalling and the role that deregulated calcium homeostasis could play in the pathogenesis of Alzheimer's disease.
早老素蛋白的突变形式会导致早发性家族性阿尔茨海默病，它能够调节多种细胞信号转导途径，其中研究最广泛的是细胞内钙信号传导。导致疾病的早老素突变可因该细胞器内的钙超载而增强肌醇（1,4,5）三磷酸（InsP3）介导的内质网释放，以及减弱储存性钙内流。我们自己的研究表明早老素具有一种新功能，即参与在InsP3调节的钙释放上游对毒蕈碱型乙酰胆碱受体刺激的磷脂酶C的调节。本文综述了早老素调节细胞内钙信号传导的机制，以及钙稳态失调在阿尔茨海默病发病机制中可能发挥的作用。
