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Cathepsin G: Localization in human cerebral cortex and generation of amyloidogenic fragments from the β-amyloid precursor protein

Savage, M.J., Iqbal, M., Loh, T., Trusko, S.P., Scott, R., Siman, R.·1994·Neuroscience
DOI 10.1016/0306-4522(94)90490-1
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Abstract

Amyloid deposits in Alzheimer's disease, Down's syndrome and aged brain are composed largely of A beta protein, which is generated by proteolytic processing of beta-amyloid precursor protein. Proteases responsible for liberating the A beta protein from the precursor have not yet been identified. Here, we examined the ability of cathepsin G, a chymotrypsin-like protease, to cleave two protease substrates: (i) a fluorogenic hexapeptide, whose sequence spans the cleavage site in the precursor for generating the A beta NH2-terminus, and (ii) recombinant human beta-amyloid precursor protein purified from a baculovirus expression system. Unlike two other members of the chymotrypsin family, cathepsin G readily degraded the hexapeptide. Furthermore, cathepsin G cleaved the beta-amyloid precursor protein to generate several breakdown products, including a prominent 11,500 mol. wt fragment immunoreactive with antibodies directed against the COOH-terminus of the protein. This COOH-terminal fragment co-migrated using two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis with C-100, a recombinant COOH-terminal segment of the beta-amyloid precursor, whose NH2-terminus is one residue upstream of the NH2-terminus of the A beta domain. We also examined the localization of cathepsin G in human brain. The distribution of cathepsin G-containing cells was examined by immunohistochemistry in the temporal cortex of both Alzheimer's and aged control samples.…

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Metadata

Authors
Savage, M. J., Iqbal, M., Loh, T., Trusko, S. P., Scott, R., & Siman, R.
Venue
Neuroscience
Publisher
Elsevier BV
Published
1994-06
Volume
60
Issue
3
Pages
607-619
ISSN
0306-4522
DOI
10.1016/0306-4522(94)90490-1
Cited by
42
References
7
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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