Alterations of chaperone protein expression in presenilin mutant neurons in response to glutamate excitotoxicity

Izumi Maezawa, Baiping Wang, Qubai Hu, George M. Martin, Lee-Way Jin, Junko Oshima

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Mutations in the presenilin-1 (PS1) gene underlie the most common form of familial dementia of the Alzheimer type (DAT). We demonstrated previously that the expression of PS1 with a M146V mutation in transgenic mice potentiates glutamate toxicity to neurons, due to an altered calcium homeostasis. Here, using a subtractive cDNA library approach, we report the identification of several genes, the altered expression of which may be associated with this unique PS1-related vulnerability to glutamate. The identified genes, including chaperonin subunit 2 and nucleophosmin 1/B23, are involved in the intracellular trafficking of proteins and ions. Northern blot analysis revealed that the effect of glutamate on calcium-binding proteins was augmented in neurons from PS1 mutation mice, compared with neurons from mice lacking other genes relevant to the pathogenesis of DAT (FE65 and APOE) or neurons from control wild-type mice. Interestingly, mRNA for two chaperone proteins were expressed at lower levels specifically in neurons from PS1 mutant mice. These findings suggest that PS1 mutations may, in part, contribute to the development of DAT via altered expression of chaperone proteins.

Original languageEnglish (US)
Pages (from-to)551-554
Number of pages4
JournalPathology International
Volume52
Issue number9
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Presenilins
Presenilin-1
Glutamic Acid
Neurons
Mutation
Proteins
Alzheimer Disease
Chaperonins
Genes
Calcium-Binding Proteins
Protein Transport
Gene Library
Northern Blotting
Transgenic Mice
Dementia
Homeostasis
Ions
Calcium
Gene Expression
Messenger RNA

Keywords

  • Alzheimer's disease
  • Calmodulin
  • Chaperone
  • Glutamate
  • Methlothionein
  • Presenilin mutation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Alterations of chaperone protein expression in presenilin mutant neurons in response to glutamate excitotoxicity. / Maezawa, Izumi; Wang, Baiping; Hu, Qubai; Martin, George M.; Jin, Lee-Way; Oshima, Junko.

In: Pathology International, Vol. 52, No. 9, 2002, p. 551-554.

Research output: Contribution to journalArticle

Maezawa, Izumi ; Wang, Baiping ; Hu, Qubai ; Martin, George M. ; Jin, Lee-Way ; Oshima, Junko. / Alterations of chaperone protein expression in presenilin mutant neurons in response to glutamate excitotoxicity. In: Pathology International. 2002 ; Vol. 52, No. 9. pp. 551-554.
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