Proteolytic Processing of β-Protein Precursor-Related Synthetic Peptides
In Alzheimer’s disease, Down’s syndrome and to a lesser extent in normal aging, abnormal proteinaceous deposits precipitate in the brain. The extracellular deposits, termed amyloid, are found in the center of senile plaques and in the blood vessel walls of the leptomeninges and the brain. In 1984, Glenner and Wong purified the amyloid fibrils from the meninges of Alzheimer’s disease (AD) and Down’s syndrome (DS) and sequenced the first 28 amino acids of the 4Kd peptide they named the β-protein (Glenner and Wong, 1984). A similar, but not identical, peptide was also purified from the amyloid cores of senile plaques (Masters et al., 1985; Selkoe et al., 1986). The β-protein is a 39–42 amino acid fragment derived from a larger, 110–135 Kd precursor protein (β-PP) whose gene has been cloned and sequenced (Goldgaber et al., 1987; Kang et al., 1987; Robakis et al., 1987; Tanzi et al., 1987a). The finding of multiple transcripts indicates alternative splicing. In addition to the β-protein, the brain amyloid contains a tightly associated serine protease inhibitor, α1-antichymotrypsin (ACT) (Abraham et al., 1988).
KeywordsDown Syndrome Amyloid Protein Precursor Amyloid Deposit Senile Plaque Amyloid Fibril
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