Twenty-nine missense mutations linked with familial Alzheimer's disease alter the processing of presenilin 1

Ohoshi Murayama, Miyuki Murayama, Toshiyuki Honda, Xiaoyan Sun, Naomi Nihonmatsu, Akihiko Takashima

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Full-length form of human presenilin 1 (PS1) is processed and an N- terminal fragment (28 KD) and C-terminal fragment (19 KD) are generated. To elucidate the possible role of presenilin mutations in Alzheimer's disease (AD), the authors analyze the effects of AD-linked mutations on PSi processing in cultured cells. Complementary DNAs encoding genes for human PS1 harboring twenty-nine missense mutations linked with familial Alzheimer's disease (FAD) were introduced into PC12 cells. Human PS1 exogenously expressed in the cells was detected by immunoblotting using a monoclonal antibody that recognized the N-terminal region of human PS1. The amounts of full-length form (48 KD) and N-terminal fragment (28 KD) of PS1 was quantified by densitometrical analysis. The ratio of the N-terminal fragment to total PSI was reduced by twenty-nine mutations. The specific effects on PS1 processing varied according to mutation. These results suggest that AD- linked missense mutations of PS1 are involved in neurodegeneration, via inhibition of PS1 processing.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume23
Issue number5
DOIs
StatePublished - Jul 1999
Externally publishedYes

Fingerprint

Presenilin-1
Missense Mutation
Alzheimer Disease
Mutation
Presenilins
PC12 Cells
Immunoblotting
Cultured Cells
Complementary DNA
Monoclonal Antibodies
human PSEN1 protein
Genes

Keywords

  • Alzheimer's disease
  • Missense mutation
  • Presenilin
  • Processing

ASJC Scopus subject areas

  • Biological Psychiatry
  • Pharmacology

Cite this

Twenty-nine missense mutations linked with familial Alzheimer's disease alter the processing of presenilin 1. / Murayama, Ohoshi; Murayama, Miyuki; Honda, Toshiyuki; Sun, Xiaoyan; Nihonmatsu, Naomi; Takashima, Akihiko.

In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 23, No. 5, 07.1999, p. 905-913.

Research output: Contribution to journalArticle

Murayama, Ohoshi ; Murayama, Miyuki ; Honda, Toshiyuki ; Sun, Xiaoyan ; Nihonmatsu, Naomi ; Takashima, Akihiko. / Twenty-nine missense mutations linked with familial Alzheimer's disease alter the processing of presenilin 1. In: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 1999 ; Vol. 23, No. 5. pp. 905-913.
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