Biological function of Presenilin and its role in AD pathogenesis
Open Access
- 17 July 2013
- journal article
- review article
- Published by Springer Nature in Translational Neurodegeneration
- Vol. 2 (1) , 15
Abstract
Presenilins (PSs) are the catalytic core of γ-secretase complex. However, the mechanism of FAD-associated PS mutations in AD pathogenesis still remains elusive. Here we review the general biology and mechanism of γ-secretase and focus on the catalytic components – presenilins and their biological functions and contributions to the AD pathogenesis. The functions of presenilins are divided into γ-secretase dependent and γ-secretase independent ones. The γ-secretase dependent functions of presenilins are exemplified by the sequential cleavages in the processing of APP and Notch; the γ-secretase independent functions of presenilins include stabilizing β-catenin in Wnt signaling pathway, regulating calcium homeostasis and their interaction with synaptic transmission.Keywords
This publication has 182 references indexed in Scilit:
- Autophagy failure in Alzheimer's disease—locating the primary defectNeurobiology of Disease, 2011
- Lysosomal Proteolysis and Autophagy Require Presenilin 1 and Are Disrupted by Alzheimer-Related PS1 MutationsCell, 2010
- Cryoelectron Microscopy Structure of Purified γ-Secretase at 12 Å ResolutionJournal of Molecular Biology, 2009
- Soluble oligomers of the amyloid β-protein impair synaptic plasticity and behaviorBehavioural Brain Research, 2008
- Mechanism of Ca2+ Disruption in Alzheimer's Disease by Presenilin Regulation of InsP3 Receptor Channel GatingNeuron, 2008
- Wnt/β-catenin signaling: new (and old) players and new insightsCurrent Opinion in Cell Biology, 2008
- Presenilins Form ER Ca2+ Leak Channels, a Function Disrupted by Familial Alzheimer's Disease-Linked MutationsCell, 2006
- Regulated Intramembrane ProteolysisCell, 2000
- Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesodermNature, 1997
- Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease geneNature, 1995