A Portrait of Alzheimer Secretases--New Features and Familiar Faces
Top Cited Papers
- 24 August 2001
- journal article
- review article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 293 (5534) , 1449-1454
- https://doi.org/10.1126/science.1064638
Abstract
The amyloid β-peptide (Aβ) is a principal component of the cerebral plaques found in the brains of patients with Alzeheimer's disease (AD). This insoluble 40– to 42–amino acid peptide is formed by the cleavage of the Aβ precursor protein (APP). The three proteases that cleave APP, α-, β-, and γ-secretases, have been implicated in the etiology of AD. β-Secretase is a membrane-anchored protein with clear homology to soluble aspartyl proteases, and α-secretase displays characteristics of certain membrane-tethered metalloproteases. γ-Secretase is apparently an oligomeric complex that includes the presenilins, which may be the catalytic component of this protease. Identification of the α-, β-, and γ-secretases provides potential targets for designing new drugs to treat AD.Keywords
This publication has 109 references indexed in Scilit:
- Endogenous Presenilin-1 Targets to Endocytic Rather Than Biosynthetic CompartmentsMolecular and Cellular Neuroscience, 2000
- Cell Surface Presenilin-1 Participates in the γ-Secretase-like Proteolysis of NotchJournal of Biological Chemistry, 1999
- Zebrafish (Danio rerio) Presenilin Promotes Aberrant Amyloid β-Peptide Production and Requires a Critical Aspartate Residue for Its Function in AmyloidogenesisBiochemistry, 1999
- An Essential Role for Ectodomain Shedding in Mammalian DevelopmentScience, 1998
- Mutations in the Transmembrane Domain of APP Altering γ-Secretase SpecificityBiochemistry, 1997
- Presenilin 1 is required for Notch 1 and Dll1 expression in the paraxial mesodermNature, 1997
- Muscarinic Regulation of Alzheimer's Disease Amyloid Precursor Protein Secretion and Amyloid β-Protein Production in Human Neuronal NT2N CellsJournal of Biological Chemistry, 1995
- Amyloid Precursor Protein Secretion via Muscarinic Receptors: Reduced Desensitization Using the M1-Selective Agonist AF102BBiochemical and Biophysical Research Communications, 1994
- Aggregation and secondary structure of synthetic amyloid βA4 peptides of Alzheimer's diseaseJournal of Molecular Biology, 1991
- Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's diseaseNature, 1991