Linked Life Data

21146496

Source:http://linkedlifedata.com/resource/pubmed/id/21146496

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-10
pubmed:abstractText
?-Secretase plays an important function in the development of Alzheimer disease, since it participates in the production of the toxic amyloid ?-peptide (A?) from the amyloid precursor protein (APP). Besides APP, ?-secretase cleaves many other substrates resulting in adverse side effects when ?-secretase inhibitors are used in clinical trials. ?-Secretase is a membrane bound protein complex consisting of at least four subunits, presenilin (PS), nicastrin, Aph-1 and Pen-2. PS and Aph-1 exist as different homologs (PS1/PS2 and Aph-1a/Aph-1b, respectively), which generates a variation in complex composition. PS1 and PS2 appears to have distinct roles since PS1 is essential during embryonic development whereas PS2 deficient mice are viable with a mild phenotype. The molecular mechanism behind this diversity is, however, largely unknown. In order to investigate whether PS1 and PS2 show different substrate specificity, we used PS1 or PS2 deficient mouse embryonic fibroblasts to study the processing on the ?-secretase substrates APP, Notch, N-cadherin, and ephrinB. We found that whereas depletion of PS1 severely affected the cleavage of all substrates, the effect of PS2 depletion was minor. In addition, less PS2 was found in active ?-secretase complexes. We also studied the effect of PS2 depletion in adult mouse brain and, in concordance with the results from the mouse embryonic fibroblasts, PS2 deficiency did not alter the cleavage of the two most important substrates, APP and Notch. In summary, this study shows that the contribution of PS2 on ?-secretase activity is of less importance, explaining the mild phenotype of PS2-deficient mice.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
404
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
564-8
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Minor contribution of presenilin 2 for ?-secretase activity in mouse embryonic fibroblasts and adult mouse brain.
pubmed:affiliation
Karolinska Institutet-Alzheimer Disease Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Novum, SE-141 86 Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't