BioSpace Collaborative

Academic/Biomedical Research
News & Jobs
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

Free Newsletters
My Subscriptions

News by Subject
News by Disease
News by Date
Search News
Post Your News

Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Pharm Country
  Bio NC
  Southern Pharm
  BioCanada East
  C2C Services & Suppliers™


Company Profiles

Research Store

Research Events
Post an Event
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Biochemistry - Neurological Disorders

Differential Regulation of Amyloid Precursor Protein/Presenilin 1 Interaction during Ab40/42 Production Detected Using Fusion Constructs
Published: Monday, November 12, 2012
Author: Naoyuki Sato et al.

by Naoyuki Sato, Masayasu Okochi, Mitsuru Shinohara, Gopal Thinakaran, Shuko Takeda, Akio Fukumori, Motoko Shinohara-Noma, Mari Mori-Ueda, Hizuki Hamada, Masatoshi Takeda, Hiromi Rakugi, Ryuichi Morishita

Beta amyloid peptides (Aß) play a key role in the pathogenesis of Alzheimer disease (AD). Presenilins (PS) function as the catalytic subunits of ?-secretase, the enzyme that releases Aß from ectodomain cleaved amyloid precursor protein (APP) by intramembrane proteolysis. Familial Alzheimer disease (FAD)-linked PSEN mutations alter APP processing in a manner that increases the relative abundance of longer Aß42 peptides to that of Aß40 peptides. The mechanisms by which Aß40 and Aß42 peptides are produced in a ratio of ten to one by wild type presenilin (PS) and by which Aß42 is overproduced by FAD-linked PS variants are not completely understood. We generated chimeras of the amyloid precursor protein C-terminal fragment (C99) and PS to address this issue. We found a chimeric protein where C99 is fused to the PS1 N-terminus undergoes in cis processing to produce Aß and that a fusion protein harboring FAD-linked PS1 mutations overproduced Aß42. To change the molecular interactions within the C99-PS1 fusion protein, we made sequential deletions of the junction between C99 and PS1. We found differential effects of deletion in C99-PS1 on Aß40 and 42 production. Deletion of the junction between APP CTF and PS1 in the fusion protein decreased Aß40, while it did not decrease Aß42 production in the presence or absence of FAD-linked PS1 mutation. These results are consistent with the idea that the APP/PS interaction is differentially regulated during Aß40 and 42 production.