Linked Life Data

21585286

Source:http://linkedlifedata.com/resource/pubmed/id/21585286

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-5-18
pubmed:abstractText
?-site APP-cleaving enzyme (BACE1) cleaves the wild type (WT) ?-site very slowly (k(cat)/K(m): 46.6 m(-1) s(-1)). Therefore we searched for additional ?-secretases and identified three cathepsins that split the WT ?-site much faster. Human cathepsin S cleaves the WT ?-site (k(cat)/K(m): 54 700 m(-1) s(-1)) 1170-fold faster than BACE1 and cathepsins B and L are 440- and 74-fold faster than BACE1, respectively. These cathepsins split two bonds flanking the WT ?-site (K-MD-A), where the K-M bond (85%) is cleaved more efficiently than the D-A bond (15%). Cleavage at the major K-M bond yields A? (amyloid ?-peptide) extended by N-terminal Met that should be removed to generate A? initiated by Asp1. The activity of cytosol and microsomal aminopeptidases on relevant peptides revealed rapid removal of N-terminal Met but not N-terminal Asp. Brain aminopeptidases showed similar specificity. Thus, aminopeptidases would convert A? extended by Met into regular A? (Asp1) found in amyloid plaques. Earlier studies indicate that A? is likely produced in the endosome and lysosome system where cathepsins S, B and L are localized and cysteine cathepsin inhibitors reduce the level of A? in cells and animals. Taken together, cathepsins S, B and L deserve further evaluation as therapeutic targets to develop disease modifying drugs to treat Alzheimer's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1437-4315
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
392
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
555-69
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Cathepsins S, B and L with aminopeptidases display ?-secretase activity associated with the pathogenesis of Alzheimer's disease.
pubmed:affiliation
Yenuvun Research Laboratory, Rehovot 76380, Israel.
pubmed:publicationType
Journal Article