The presenilins

Mark P. Mattson, Qing Guo

Research output: Contribution to journalArticle

Abstract

Presenilin-1 and presenilin-2 are highly homologous genes located on chromosomes 14 and 1, respectively, that have recently been linked to some cases of early-onset autosomal dominant inherited forms of Alzheimer's disease (AD). Presenilins are integral membrane proteins localized in the endoplasmic reticulum of neurons throughout the nervous system. Studies of presenilin-1 knockout mice, and of invertebrate homologues of presenilins and their interacting proteins, suggest major roles for presenilins in normal development. Presenilin-1 mutant knockin mice do not exhibit developmental abnormalities, which indicates that the pathogenic mechanism of presenilin mutations involves gain of an adverse property of the mutant protein. Expression of presenilin mutations in cultured neurons and transgenic mice results in increased sensitivity to apoptosis induced by trophic factor withdrawal and exposure to oxidative and metabolic insults, and also alters gene expression. The pathogenic mechanism of presenilin mutations may involve perturbed endoplasmic reticulum calcium homeostasis resulting in enhanced oxidative stress, altered proteolytic processing of the amyloid precursor protein (APP), and increased neuronal vulnerability to excitotoxicity. Studies of presenilins are rapidly increasing our understanding the molecular and cellular underpinnings of AD and are also elucidating novel roles of the endoplasmic reticulum in neuronal plasticity and cell death.

Original languageEnglish (US)
Pages (from-to)112-124
Number of pages13
JournalNeuroscientist
Volume5
Issue number2
StatePublished - Mar 1999
Externally publishedYes

Fingerprint

Presenilins
Presenilin-1
Endoplasmic Reticulum
Mutation
Alzheimer Disease
Presenilin-2
Neurons
Chromosomes, Human, Pair 14
Neuronal Plasticity
Amyloid beta-Protein Precursor
Chromosomes, Human, Pair 1
Mutant Proteins
Invertebrates
Knockout Mice
Nervous System
Transgenic Mice
Membrane Proteins
Oxidative Stress
Homeostasis
Cell Death

Keywords

  • Amyloid β-peptide
  • Apoptosis
  • Excitotoxicity
  • Mitochondrial transmembrane potential
  • Muscarinic cholinergic
  • Reactive oxygen species

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mattson, M. P., & Guo, Q. (1999). The presenilins. Neuroscientist, 5(2), 112-124.

The presenilins. / Mattson, Mark P.; Guo, Qing.

In: Neuroscientist, Vol. 5, No. 2, 03.1999, p. 112-124.

Research output: Contribution to journalArticle

Mattson, MP & Guo, Q 1999, 'The presenilins', Neuroscientist, vol. 5, no. 2, pp. 112-124.
Mattson MP, Guo Q. The presenilins. Neuroscientist. 1999 Mar;5(2):112-124.
Mattson, Mark P. ; Guo, Qing. / The presenilins. In: Neuroscientist. 1999 ; Vol. 5, No. 2. pp. 112-124.
@article{dbb1e3bc6d614a1a953bccfe05740c91,
title = "The presenilins",
abstract = "Presenilin-1 and presenilin-2 are highly homologous genes located on chromosomes 14 and 1, respectively, that have recently been linked to some cases of early-onset autosomal dominant inherited forms of Alzheimer's disease (AD). Presenilins are integral membrane proteins localized in the endoplasmic reticulum of neurons throughout the nervous system. Studies of presenilin-1 knockout mice, and of invertebrate homologues of presenilins and their interacting proteins, suggest major roles for presenilins in normal development. Presenilin-1 mutant knockin mice do not exhibit developmental abnormalities, which indicates that the pathogenic mechanism of presenilin mutations involves gain of an adverse property of the mutant protein. Expression of presenilin mutations in cultured neurons and transgenic mice results in increased sensitivity to apoptosis induced by trophic factor withdrawal and exposure to oxidative and metabolic insults, and also alters gene expression. The pathogenic mechanism of presenilin mutations may involve perturbed endoplasmic reticulum calcium homeostasis resulting in enhanced oxidative stress, altered proteolytic processing of the amyloid precursor protein (APP), and increased neuronal vulnerability to excitotoxicity. Studies of presenilins are rapidly increasing our understanding the molecular and cellular underpinnings of AD and are also elucidating novel roles of the endoplasmic reticulum in neuronal plasticity and cell death.",
keywords = "Amyloid β-peptide, Apoptosis, Excitotoxicity, Mitochondrial transmembrane potential, Muscarinic cholinergic, Reactive oxygen species",
author = "Mattson, {Mark P.} and Qing Guo",
year = "1999",
month = "3",
language = "English (US)",
volume = "5",
pages = "112--124",
journal = "Neuroscientist",
issn = "1073-8584",
publisher = "SAGE Publications Inc.",
number = "2",

}

TY - JOUR

T1 - The presenilins

AU - Mattson, Mark P.

AU - Guo, Qing

PY - 1999/3

Y1 - 1999/3

N2 - Presenilin-1 and presenilin-2 are highly homologous genes located on chromosomes 14 and 1, respectively, that have recently been linked to some cases of early-onset autosomal dominant inherited forms of Alzheimer's disease (AD). Presenilins are integral membrane proteins localized in the endoplasmic reticulum of neurons throughout the nervous system. Studies of presenilin-1 knockout mice, and of invertebrate homologues of presenilins and their interacting proteins, suggest major roles for presenilins in normal development. Presenilin-1 mutant knockin mice do not exhibit developmental abnormalities, which indicates that the pathogenic mechanism of presenilin mutations involves gain of an adverse property of the mutant protein. Expression of presenilin mutations in cultured neurons and transgenic mice results in increased sensitivity to apoptosis induced by trophic factor withdrawal and exposure to oxidative and metabolic insults, and also alters gene expression. The pathogenic mechanism of presenilin mutations may involve perturbed endoplasmic reticulum calcium homeostasis resulting in enhanced oxidative stress, altered proteolytic processing of the amyloid precursor protein (APP), and increased neuronal vulnerability to excitotoxicity. Studies of presenilins are rapidly increasing our understanding the molecular and cellular underpinnings of AD and are also elucidating novel roles of the endoplasmic reticulum in neuronal plasticity and cell death.

AB - Presenilin-1 and presenilin-2 are highly homologous genes located on chromosomes 14 and 1, respectively, that have recently been linked to some cases of early-onset autosomal dominant inherited forms of Alzheimer's disease (AD). Presenilins are integral membrane proteins localized in the endoplasmic reticulum of neurons throughout the nervous system. Studies of presenilin-1 knockout mice, and of invertebrate homologues of presenilins and their interacting proteins, suggest major roles for presenilins in normal development. Presenilin-1 mutant knockin mice do not exhibit developmental abnormalities, which indicates that the pathogenic mechanism of presenilin mutations involves gain of an adverse property of the mutant protein. Expression of presenilin mutations in cultured neurons and transgenic mice results in increased sensitivity to apoptosis induced by trophic factor withdrawal and exposure to oxidative and metabolic insults, and also alters gene expression. The pathogenic mechanism of presenilin mutations may involve perturbed endoplasmic reticulum calcium homeostasis resulting in enhanced oxidative stress, altered proteolytic processing of the amyloid precursor protein (APP), and increased neuronal vulnerability to excitotoxicity. Studies of presenilins are rapidly increasing our understanding the molecular and cellular underpinnings of AD and are also elucidating novel roles of the endoplasmic reticulum in neuronal plasticity and cell death.

KW - Amyloid β-peptide

KW - Apoptosis

KW - Excitotoxicity

KW - Mitochondrial transmembrane potential

KW - Muscarinic cholinergic

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=0032964702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032964702&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0032964702

VL - 5

SP - 112

EP - 124

JO - Neuroscientist

JF - Neuroscientist

SN - 1073-8584

IS - 2

ER -