Abstract
EXTRACELLULAR deposition of amyloid β-protein (β-AP), or A4 protein (Mr 4,000), is associated with Alzheimer's disease and with Down's syndrome (trisomy for chromosome 21)1–3. The large membrane-bound precursor protein (APP) of β-AP is normally cleaved within the β-AP region by a putative proteinase (APP secretase) to release its extracellular portion; β-AP is produced by an alternative proteolytic processing4–6. Here we demonstrate that APP contains a proteinase inhibitor domain for the matrix metalloproteinase gelatinase A, which is located in the C-terminal glycosylated region of the secretory forms of APP. In addition, we show that the gelatinase has an APP secretase-like activity, which hydrolyses the Lys l6-Leu l7 bond in the β-AP sequence. Our results indicate that the proteinase inhibitor domain of APP and gelatinase A may be involved in the formation of β-AP.
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Miyazaki, K., Hasegawa, M., Funahashi, K. et al. A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor. Nature 362, 839–841 (1993). https://doi.org/10.1038/362839a0
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DOI: https://doi.org/10.1038/362839a0
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