Characterization of human presenilin 1 using N-terminal specific monoclonal antibodies: Evidence that Alzheimer mutations affect proteolytic processing.

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 Mr 47000 and a more abundant Mr 28000 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Mercken M,Takahashi H,Honda T,Sato K,Murayama M,Nakazato Y,Noguchi K,Imahori K,Takashima A

doi

10.1016/0014-5793(96)00608-4

subject

Has Abstract

pub_date

1996-07-08 00:00:00

pages

297-303

issue

3

eissn

0014-5793

issn

1873-3468

pii

0014-5793(96)00608-4

journal_volume

389

pub_type

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