Studies on the proteolytic degradation of the β-protein precursor by proteases purified from Alzheimer's disease brain

C. R. Abraham, B. L. Razzaboni, S. S. Sisodia, E. H. Koo, D. L. Price, W. E. Van Nostrand, G. Papastoitsis

Research output: Contribution to journalArticle

Abstract

In Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis of Dutch origin, and normal aging, amyloid accumulates in the brain parenchyma and blood vessels. The major protein in the deposits is the β-protein, a 4-kD peptide possibly generated by an abnormal degradation of its precursor, the β-protein precursor (βPP). We found, as a second component of the brain amyloid, the serine protease inhibitor α1- antichymotrypsin (ACT). Inasmuch as ACT is tightly associated with the β- protein and is never found in other amyloidoses, we hypothesized a role for ACT in the degradation of the βPP. We used synthetic peptides made according to the sequence flanking the N-terminus of the β-protein to screen brain fractions for protease activity. After several purification steps, two protease fractions were found that can cleave the peptide between methionine and aspartic acid, aspartic acid being the N-terminus of the β-protein. One protease is activated by calcium and inhibited by ACT, βPP containing the Kunitz-type inhibitory domain, diisofluorophosphate, and 1,10-phenanthroline. This protease fraction is also able to degrade the βPP in vitro. The second protease is a metal-dependent cysteine protease.

Original languageEnglish (US)
Pages (from-to)161-165
Number of pages5
JournalAnnals of the New York Academy of Sciences
Volume640
DOIs
StatePublished - Jan 1 1991

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Abraham, C. R., Razzaboni, B. L., Sisodia, S. S., Koo, E. H., Price, D. L., Van Nostrand, W. E., & Papastoitsis, G. (1991). Studies on the proteolytic degradation of the β-protein precursor by proteases purified from Alzheimer's disease brain. Annals of the New York Academy of Sciences, 640, 161-165. https://doi.org/10.1111/j.1749-6632.1991.tb00209.x