Source:http://linkedlifedata.com/resource/pubmed/id/16164418
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2005-9-16
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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.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin B,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Endopeptidases
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1431-6730
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
386
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
931-40
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16164418-Alzheimer Disease,
pubmed-meshheading:16164418-Amino Acid Sequence,
pubmed-meshheading:16164418-Amyloid Precursor Protein Secretases,
pubmed-meshheading:16164418-Amyloid beta-Peptides,
pubmed-meshheading:16164418-Animals,
pubmed-meshheading:16164418-Cathepsin B,
pubmed-meshheading:16164418-Cattle,
pubmed-meshheading:16164418-Chromaffin Cells,
pubmed-meshheading:16164418-Cysteine Endopeptidases,
pubmed-meshheading:16164418-Cysteine Proteinase Inhibitors,
pubmed-meshheading:16164418-Endopeptidases,
pubmed-meshheading:16164418-Molecular Sequence Data,
pubmed-meshheading:16164418-Neurons,
pubmed-meshheading:16164418-Secretory Vesicles
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pubmed:year |
2005
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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.
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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
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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