Linked Life Data

12052174

Source:http://linkedlifedata.com/resource/pubmed/id/12052174

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2002-6-7
pubmed:abstractText
A considerable body of evidence has accumulated in recent years implicating the beta-amyloid protein (Abeta) in the etiology of Alzheimer s disease (AD). The highly hydrophobic Abeta can nucleate and form neurotoxic fibrils that are the principal components of the cerebral plaques characteristic of AD. Abeta is formed from the amyloid-beta precursor protein (APP) through two protease activities. First, beta-secretase cleaves APP at the Abeta N-terminus, resulting in a soluble, secreted APP derivative (beta-APPs) and a 12 kDa membrane-retained C-terminal fragment. The latter is further processed to Abeta by gamma secretases, which cleave within the single transmembrane region. Other APP molecules can be cleaved by alpha-secretase within the Abeta region, thus precluding Abeta formation. Both beta- and gamma- secretase have become prime targets for the development of therapeutic agent that reduce Abeta production. Beta-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 gamma-secretases, novel intramembrane-cleaving aspartyl proteases activated through autoproteolysis. In this article, we review the current knowledge of gamma-secretase biochemistry and cell biology and the development of inhibitors of this important therapeutic target.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0929-8673
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1087-106
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
The search for gamma-secretase and development of inhibitors.
pubmed:affiliation
PPG Industrial, 440 College Park Drive, Monroeville, PA 15146, USA. jytsai@ppg.com
pubmed:publicationType
Journal Article, Review