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PMID: 12429067 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The presenilins.

Genome biology ·Vol. 3 ·No. 11 ·2002-10-23 ·Pages reviews3014

Tandon A, Fraser P

Abstract

The presenilins are evolutionarily conserved transmembrane proteins that regulate cleavage of certain other proteins in their transmembrane domains. The clinical significance of this regulation is shown by the contribution of presenilin mutations to 20-50% of early-onset cases of inherited Alzheimer's disease. Although the precise molecular mechanism underlying presenilin function or dysfunction remains elusive, presenilins are thought to be part of a complex of proteins that has 'gamma-secretase cleavage' activity, which is clearly central in the pathogenesis of Alzheimer's disease. Mutations in presenilins increase the production of the longer isoforms of amyloid beta peptide, which are neurotoxic and prone to self-aggregation. Biochemical studies indicate that the presenilins do not act alone but operate within large heteromeric protein complexes, whose components and enzymatic core are the subject of much study and controversy; one essential component is nicastrin. The presenilin primary sequence is remarkably well conserved in eukaryotes, suggesting some functional conservation; indeed, defects caused by mutations in the nemotode presenilin homolog can be rescued by human presenilin.

MeSH Terms
Alzheimer Disease/enzymology,genetics Amyloid Precursor Protein Secretases Amyloid beta-Protein Precursor/metabolism Animals Aspartic Acid Endopeptidases/genetics,metabolism,physiology Endopeptidases/genetics,metabolism,physiology Evolution, Molecular Humans Membrane Proteins/chemistry,genetics,metabolism,physiology Mutation/genetics Organ Specificity/genetics,physiology Presenilin-1 Presenilin-2
Chemicals
Amyloid beta-Protein Precursor Membrane Proteins PSEN1 protein, human PSEN2 protein, human Presenilin-1 Presenilin-2 Amyloid Precursor Protein Secretases Endopeptidases Aspartic Acid Endopeptidases BACE2 protein, human BACE1 protein, human
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tandon Anurag
Centre for Research in Neurodegenerative Diseases, University of Toronto, Queen's Park Crescent West, Toronto M5S 3H2, Canada. a.tandon@utoronto.ca
Fraser Paul
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Article Info
Journal
Genome biology
Abbr.
Genome Biol
ISSN
1474-760X
DOI
10.1186/gb-2002-3-11-reviews3014
Email
a.tandon@utoronto.ca
Published
2002-10-23
Epub
2002-00-23
Pages
reviews3014
Language
English
Region
England
NLM ID
100960660
PMCID
PMC244923
Subset
IM
External Links
PubMed source DOI: 10.1186/gb-2002-3-11-reviews3014 PMC Full Text View journal details
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