Presenilin-mediated signal transduction.
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.
Cowburn
Richard F
RF
Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, KI-Alzheimer's Disease Research Center, Novum, plan 5, S-141 57 Huddinge, Sweden. richard.cowburn@astrazeneca.com
Popescu
Bogdan O
BO
Ankarcrona
Maria
M
Dehvari
Nodi
N
Cedazo-Minguez
Angel
A
D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D053763:Presenilins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology
D053763:Presenilins; D010738:Type C Phospholipases