Deletion of presenilin 1 hydrophilic loop sequence leads to impaired gamma-secretase activity and exacerbated amyloid pathology.

ABSTRACT: gamma-Secretase processing of the amyloid precursor protein (APP) generates Abeta40 and Abeta42, peptides that constitute the principal components of the beta-amyloid plaque pathology of Alzheimer's disease (AD). The gamma-secretase activity is executed by a high-molecular-weight complex of which presenilin 1 (PS1) is an essential component. PS1 is a multi-pass membrane protein, and the large hydrophilic loop domain between transmembrane domains 6 and 7 has been shown to interact with various proteins. To determine the physiological function of the loop domain, we created a strain of PS1 knock-in mice in which the exon 10, which encodes most of the hydrophilic loop sequence, was deleted from the endogenous PS1 gene. We report here that the homozygous exon 10-deleted mice are viable but exh

SUBMITTER: Deng Y 

PROVIDER: S-EPMC6674120 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature