Linked Life Data

10816583

Source:http://linkedlifedata.com/resource/pubmed/id/10816583

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pubmed-article:10816583pubmed:abstractTextPresenilins (PSs) are polytopic membrane proteins that have been implicated as potential therapeutic targets in Alzheimer's disease because of their role in regulating the gamma-secretase cleavage that generates the amyloid beta protein (Abeta). It is not clear how PSs regulate gamma-secretase cleavage, but there is evidence that PSs could be either essential cofactors in the gamma-secretase cleavage, gamma-secretase themselves, or regulators of intracellular trafficking that indirectly influence gamma-secretase cleavage. Using presenilin 1 (PS1) mutants that inhibit Abeta production in conjunction with transmembrane domain mutants of the amyloid protein precursor that are cleaved by pharmacologically distinct gamma-secretases, we show that PS1 regulates multiple pharmacologically distinct gamma-secretase activities as well as inducible alpha-secretase activity. It is likely that PS1 acts indirectly to regulate these activities (as in a trafficking or chaperone role), because these data indicate that for PS1 to be gamma-secretase it must either have multiple active sites or exist in a variety of catalytically active forms that are altered to an equivalent extent by the mutations we have studied.lld:pubmed
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pubmed-article:10816583pubmed:articleTitlePresenilin 1 regulates pharmacologically distinct gamma -secretase activities. Implications for the role of presenilin in gamma -secretase cleavage.lld:pubmed
pubmed-article:10816583pubmed:affiliationMayo Clinic Jacksonville, Department of Pharmacology, Jacksonville, Florida 32224, USA.lld:pubmed
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pubmed-article:10816583pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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