Characterization of human presenilin 1 using N‐terminal specific monoclonal antibodies: Evidence that Alzheimer mutations affect proteolytic processing
- 8 July 1996
- journal article
- Published by Wiley in FEBS Letters
- Vol. 389 (3), 297-303
- https://doi.org/10.1016/0014-5793(96)00608-4
Abstract
The majority of cases of early-onset familial Alzheimer disease are caused by mutations in the recently identified presenilin 1 (PS1) gene, located on chromosome 14. PS1, a 467 amino acid protein, is predicted to be an integral membrane protein containing seven putative transmembrane domains and a large hydrophilic loop between the sixth and seventh membrane-spanning domain. We produced 7 monoclonal antibodies that react with 3 non-overlapping epitopes on the N-terminal hydrophilic tail of PS1. The monoclonal antibodies can detect the full-size PS1 at M r 47 000 and a more abundant M r 28 000 product in membrane extracts from human brain and human cell lines. PC12 cells transiently transfected with PS1 constructs containing two different Alzheimer mutations fail to generate the 28 kDa degradation product in contrast to PC12 cells transfected with wild-type PS1. Our results indicate that missense mutations in this form of familial Alzheimer disease may act via a mechanism of impaired proteolytic processing of PS1.Keywords
This publication has 21 references indexed in Scilit:
- Identification and characterization of presenilin I‐467, I‐463 and I‐374FEBS Letters, 1996
- Genetic association between intronic polymorphism in presenilin-1 gene and late-onset Alzheimer's diseaseThe Lancet, 1996
- Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3Human Molecular Genetics, 1995
- A mutation in Alzheimerʼs disease destroying a splice acceptor site in the presenilin-1 geneNeuroReport, 1995
- Presenilins and Alzheimer diseaseNature Genetics, 1995
- The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD familiesNature Genetics, 1995
- Missense mutation of S182 gene in Japanese familial Alzheimer's diseaseThe Lancet, 1995
- Misserise mutation of S182 gene in Italian families with early-onset Alzheimer's diseaseThe Lancet, 1995
- Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's diseaseNature, 1991
- In vitro and in vivo products of E. coli lactose permease gene are identicalNature, 1980