Skip to main content

The Search for γ-Secretase and Development of Inhibitors

Buy Article:

$55.00 plus tax (Refund Policy)

A considerable body of evidence has accumulated in recent years implicating the ß-amyloid protein (Aß) in the etiology of Alzheimer's disease (AD). The highly hydrophobic Aß can nucleate and form neurotoxic fibrils that are the principal components of the cerebral plaques characteristic of AD. Aß is formed from the amyloid-ßprecursor protein (APP) through two protease activities. First, ß-secretase cleaves APP at the Aß N-terminus, resulting in a soluble, secreted APP derivative (ß-APPs) and a 12 kDa membrane-retained C-terminal fragment. The latter is further processed to Aß by γ secretases, which cleave within the single transmembrane region. Other APP molecules can be cleaved by α-secretase within the Aß region, thus precluding Aß formation. Both β- and γ- secretase have become prime targets for the development of therapeutic agent that reduce Aβ production. β-Secretase has recently been identified as a new membrane-anchored aspartyl protease in the cathepsin D family. Inhibitor profiling, site-directed mutagenesis, and affinity labeling together have suggested that the multi-pass presenilins are γ-secretases, novel intramembrane-cleaving aspartyl proteases activated through autoproteolysis. In this article, we review the current knowledge of γ-secretase biochemistry and cell biology and the development of inhibitors of this important therapeutic target.
No References
No Citations
No Supplementary Data
No Data/Media
No Metrics

Keywords: ad and gamma secretase; app mutation; difluororetone peptidomimetics; gamma secretase; gamma secretase and inhibitors; golde; ps mutation

Document Type: Review Article

Publication date: 2002-06-01

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more