title: Twenty-nine missense mutations linked with familial Alzheimer's disease alter the processing of presenilin 1.
abstract: 1. 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 PS1 processing in cultured cells. 2. 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. 3. The ratio of the N-terminal fragment to total PS1 was reduced by twenty-nine mutations. The specific effects on PS1 processing varied according to mutation. 4. These results suggest that AD-linked missense mutations of PS1 are involved in neurodegeneration via inhibition of PS1 processing.
authors.affiliation: Laboratory for Alzheimer's Disease, Brain Science Institute, RIKEN, Saitama, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Murayama
authors.forename: M
authors.initials: M
authors.lastname: Murayama
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.forename: N
authors.initials: N
authors.lastname: Nihonmatsu
authors.forename: A
authors.initials: A
authors.lastname: Takashima
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D020125:Mutation, Missense / Q000235:genetics*; D016716:PC12 Cells; D053764:Presenilin-1; D051381:Rats; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1