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A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor

Nature volume 362, pages 839841 (29 April 1993) | Download Citation

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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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  1. Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, 2-120-3 Nakamura-cho, Minami-ku, Yokohama 232, Japan

    • Kaoru Miyazaki
    • , Miki Hasegawa
    • , Kayano Funahashi
    •  & Makoto Umeda

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https://doi.org/10.1038/362839a0

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