The large hydrophilic loop of presenilin 1 is important for regulating gamma-secretase complex assembly and dictating the amyloid beta peptide (Abeta) Profile without affecting Notch processing.

ABSTRACT: Gamma-secretase is an enzyme complex that mediates both Notch signaling and beta-amyloid precursor protein (APP) processing, resulting in the generation of Notch intracellular domain, APP intracellular domain, and the amyloid beta peptide (Abeta), the latter playing a central role in Alzheimer disease (AD). By a hitherto undefined mechanism, the activity of gamma-secretase gives rise to Abeta peptides of different lengths, where Abeta42 is considered to play a particular role in AD. In this study we have examined the role of the large hydrophilic loop (amino acids 320-374, encoded by exon 10) of presenilin 1 (PS1), the catalytic subunit of gamma-secretase, for gamma-secretase complex formation and activity on Notch and APP processing. Deletion of exon 10 resulted in impaired PS1 endoproteo

SUBMITTER: Wanngren J 

PROVIDER: S-EPMC2838274 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature