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Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
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Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid

H Koike1, S Tomioka, H Sorimachi

  • 1Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.

The Biochemical Journal
|October 8, 1999
PubMed

Insights

Meltrin gamma (MDC9), a metalloprotease, exhibits alpha-secretase-like activity. Phorbol ester treatment activates MDC9, influencing amyloid precursor protein processing and suggesting a role in its cleavage.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • MDC9 (meltrin gamma) is a membrane-anchored metalloprotease with multiple domains.
  • Metalloproteases play crucial roles in protein processing and signaling pathways.

Purpose of the Study:

  • To investigate the enzymatic activity and function of MDC9.
  • To determine the effect of MDC9 on amyloid precursor protein (APP) processing.

Main Methods:

  • Expression of MDC9 and APP695 in COS cells.
  • Treatment with phorbol ester and a metalloprotease inhibitor (SI-27).
  • Analysis of APP cleavage products using cell culture techniques.

Main Results:

  • MDC9 undergoes cleavage between its prodomain and metalloprotease domain.
  • MDC9 expression promotes alpha-secretase-like cleavage of APP695.
  • Inhibition of MDC9 activity enhances beta-secretase cleavage of APP.

Conclusions:

  • MDC9 possesses alpha-secretase-like activity.
  • MDC9 activity is modulated by phorbol ester treatment.
  • MDC9 plays a role in regulating APP processing pathways.

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