Linked Life Data

11966461

Source:http://linkedlifedata.com/resource/pubmed/id/11966461

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-4-22
pubmed:abstractText
The amyloid-beta peptide (Abeta) is the major protein component of the characteristic cerebral plaques of Alzheimer s disease (AD), and a large body of evidence supports a pathogenic role for this peptide. Thus, the proteases beta- and gamma-secretase that are responsible for carving Abeta out of its precursor protein are considered prime targets for therapeutic design. beta-Secretase is a membrane-anchored aspartyl protease of the pepsin family, while gamma-secretase is much more complex. gamma-Secretase requires presenilin, a multipass membrane protein that is the site of dozens of missense mutations that alter Abeta formation and cause hereditary AD. Two conserved aspartates in presenilin are required for gamma-secretase activity, and aspartyl protease transition-state analogue inhibitors of gamma-secretase bind directly to presenilins, strong evidence that presenilin is the catalytic component of a novel membrane aspartyl protease. gamma-Secretase appears to be a multi-component complex of integral membrane proteins, and so far presenilin and a single-pass membrane protein called nicastrin have been identified as members of this complex. A closely similar or identical protease activity is essential for a signaling pathway critical for embryogenesis and hematopoiesis, raising concerns about gamma-secretase as a target. The development of potent and selective inhibitors with good pharmacokinetic properties may soon address these concerns.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases, http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor, http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/BACE1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Molecular Probes, http://linkedlifedata.com/resource/pubmed/chemical/PSEN1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PSEN2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-1, http://linkedlifedata.com/resource/pubmed/chemical/Presenilin-2, http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1568-0266
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
371-83
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Secretase as a target for Alzheimer's disease.
pubmed:affiliation
Center for Neurologic Diseases, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, H.I.M. 626, Boston, MA 02115, USA. mwolfe@rics.bwh.harvard.edu
pubmed:publicationType
Journal Article, Review