Pathological and physiological functions of presenilins

Mutations in PSEN1 and PSEN2 genes account for the majority of cases of early-onset familial Alzheimer disease. Since the first prediction of a genetic link between PSEN1 and PSEN2 with Alzheimer's disease, many research groups from both academia and pharmaceutical industry have sought to unrav...

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Main Authors:	Vetrivel, Kulandaivelu S, Zhang, Yun-wu, Xu, Huaxi, Thinakaran, Gopal
Format:	Online
Language:	English
Published:	BioMed Central 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1513131/

id	pubmed-1513131
recordtype	oai_dc
spelling	pubmed-15131312006-07-20 Pathological and physiological functions of presenilins Vetrivel, Kulandaivelu S Zhang, Yun-wu Xu, Huaxi Thinakaran, Gopal Review Mutations in PSEN1 and PSEN2 genes account for the majority of cases of early-onset familial Alzheimer disease. Since the first prediction of a genetic link between PSEN1 and PSEN2 with Alzheimer's disease, many research groups from both academia and pharmaceutical industry have sought to unravel how pathogenic mutations in PSEN cause presenile dementia. PSEN genes encode polytopic membrane proteins termed presenilins (PS1 and PS2), which function as the catalytic subunit of γ-secretase, an intramembrane protease that has a wide spectrum of type I membrane protein substrates. Sequential cleavage of amyloid precursor protein by BACE and γ-secretase releases highly fibrillogenic β-amyloid peptides, which accumulate in the brains of aged individuals and patients with Alzheimer's disease. Familial Alzheimer's disease-associated presenilin variants are thought to exert their pathogenic function by selectively elevating the levels of highly amyloidogenic Aβ42 peptides. In addition to Alzheimer's disease, several recent studies have linked PSEN1 to familiar frontotemporal dementia. Here, we review the biology of PS1, its role in γ-secretase activity, and discuss recent developments in the cell biology of PS1 with respect to Alzheimer's disease pathogenesis. BioMed Central 2006-06-12 /pmc/articles/PMC1513131/ /pubmed/16930451 http://dx.doi.org/10.1186/1750-1326-1-4 Text en Copyright © 2006 Vetrivel et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Vetrivel, Kulandaivelu S Zhang, Yun-wu Xu, Huaxi Thinakaran, Gopal
spellingShingle	Vetrivel, Kulandaivelu S Zhang, Yun-wu Xu, Huaxi Thinakaran, Gopal Pathological and physiological functions of presenilins
author_facet	Vetrivel, Kulandaivelu S Zhang, Yun-wu Xu, Huaxi Thinakaran, Gopal
author_sort	Vetrivel, Kulandaivelu S
title	Pathological and physiological functions of presenilins
title_short	Pathological and physiological functions of presenilins
title_full	Pathological and physiological functions of presenilins
title_fullStr	Pathological and physiological functions of presenilins
title_full_unstemmed	Pathological and physiological functions of presenilins
title_sort	pathological and physiological functions of presenilins
description	Mutations in PSEN1 and PSEN2 genes account for the majority of cases of early-onset familial Alzheimer disease. Since the first prediction of a genetic link between PSEN1 and PSEN2 with Alzheimer's disease, many research groups from both academia and pharmaceutical industry have sought to unravel how pathogenic mutations in PSEN cause presenile dementia. PSEN genes encode polytopic membrane proteins termed presenilins (PS1 and PS2), which function as the catalytic subunit of γ-secretase, an intramembrane protease that has a wide spectrum of type I membrane protein substrates. Sequential cleavage of amyloid precursor protein by BACE and γ-secretase releases highly fibrillogenic β-amyloid peptides, which accumulate in the brains of aged individuals and patients with Alzheimer's disease. Familial Alzheimer's disease-associated presenilin variants are thought to exert their pathogenic function by selectively elevating the levels of highly amyloidogenic Aβ42 peptides. In addition to Alzheimer's disease, several recent studies have linked PSEN1 to familiar frontotemporal dementia. Here, we review the biology of PS1, its role in γ-secretase activity, and discuss recent developments in the cell biology of PS1 with respect to Alzheimer's disease pathogenesis.
publisher	BioMed Central
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1513131/
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Pathological and physiological functions of presenilins

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