pubmed-article:16164418 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0002395 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0376604 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0699919 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0521390 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0886515 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C1454853 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0392756 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0033268 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C0332120 | lld:lifeskim |
pubmed-article:16164418 | lifeskim:mentions | umls-concept:C2353566 | lld:lifeskim |
pubmed-article:16164418 | pubmed:issue | 9 | lld:pubmed |
pubmed-article:16164418 | pubmed:dateCreated | 2005-9-16 | lld:pubmed |
pubmed-article:16164418 | pubmed:abstractText | The regulated secretory pathway of neurons is the major source of extracellular A beta that accumulates in Alzheimer's disease (AD). Extracellular A beta secreted from that pathway is generated by beta-secretase processing of amyloid precursor protein (APP). Previously, cysteine protease activity was demonstrated as the major beta-secretase activity in regulated secretory vesicles of neuronal chromaffin cells. In this study, the representative cysteine protease activity in these secretory vesicles was purified and identified as cathepsin B by peptide sequencing. Immunoelectron microscopy demonstrated colocalization of cathepsin B with A beta in these vesicles. The selective cathepsin B inhibitor, CA074, blocked the conversion of endogenous APP to A beta in isolated regulated secretory vesicles. In chromaffin cells, CA074Me (a cell permeable form of CA074) reduced by about 50% the extracellular A beta released by the regulated secretory pathway, but CA074Me had no effect on A beta released by the constitutive pathway. Furthermore, CA074Me inhibited processing of APP into the COOH-terminal beta-secretase-like cleavage product. These results provide evidence for cathepsin B as a candidate beta-secretase in regulated secretory vesicles of neuronal chromaffin cells. These findings implicate cathepsin B as beta-secretase in the regulated secretory pathway of brain neurons, suggesting that inhibitors of cathepsin B may be considered as therapeutic agents to reduce A beta in AD. | lld:pubmed |
pubmed-article:16164418 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16164418 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16164418 | pubmed:language | eng | lld:pubmed |
pubmed-article:16164418 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16164418 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:16164418 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16164418 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16164418 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16164418 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16164418 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16164418 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:16164418 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:16164418 | pubmed:month | Sep | lld:pubmed |
pubmed-article:16164418 | pubmed:issn | 1431-6730 | lld:pubmed |
pubmed-article:16164418 | pubmed:author | pubmed-author:BogyoMatthewM | lld:pubmed |
pubmed-article:16164418 | pubmed:author | pubmed-author:Medzihradszky... | lld:pubmed |
pubmed-article:16164418 | pubmed:author | pubmed-author:ToneffThomasT | lld:pubmed |
pubmed-article:16164418 | pubmed:author | pubmed-author:ReisineTerryT | lld:pubmed |
pubmed-article:16164418 | pubmed:author | pubmed-author:HookVivianV | lld:pubmed |
pubmed-article:16164418 | pubmed:author | pubmed-author:GreenbaumDoro... | lld:pubmed |
pubmed-article:16164418 | pubmed:author | pubmed-author:LaneWilliamW | lld:pubmed |
pubmed-article:16164418 | pubmed:author | pubmed-author:NeveuJohnJ | lld:pubmed |
pubmed-article:16164418 | pubmed:author | pubmed-author:HookGregoryG | lld:pubmed |
pubmed-article:16164418 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:16164418 | pubmed:volume | 386 | lld:pubmed |
pubmed-article:16164418 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:16164418 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:16164418 | pubmed:pagination | 931-40 | lld:pubmed |
pubmed-article:16164418 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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pubmed-article:16164418 | pubmed:meshHeading | pubmed-meshheading:16164418... | lld:pubmed |
pubmed-article:16164418 | pubmed:year | 2005 | lld:pubmed |
pubmed-article:16164418 | pubmed:articleTitle | Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer's disease. | lld:pubmed |
pubmed-article:16164418 | pubmed:affiliation | Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA 92093, USA. vhook@ucsd.edu | lld:pubmed |
pubmed-article:16164418 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:16164418 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
pubmed-article:16164418 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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