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Amyloid beta/A4 precursor protein (APP) processing in lysosomes.

K Tagawa1, K Maruyama, S Ishiura

  • 1National Institute of Neuroscience, NCNP, Tokyo, Japan.

Annals of the New York Academy of Sciences
|December 31, 1992
PubMed
Summary
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Cathepsin B acts as an enzyme in processing amyloid precursor protein (APP), potentially contributing to Alzheimer's disease pathogenesis by cleaving APP into specific fragments.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Molecular Biology

Background:

  • Alzheimer's disease (AD) is linked to amyloid beta protein plaques.
  • Amyloid precursor protein (APP) processing is crucial in AD pathogenesis.

Purpose of the Study:

  • To investigate the role of cathepsin B as a potential secretase for APP.
  • To determine if lysosomal cathepsin B is involved in constitutive APP processing.

Main Methods:

  • Utilized APP-transfected COS-1 cells for experimental analysis.
  • Conducted digestion experiments to assess cathepsin B activity on APP.

Main Results:

  • Confirmed cathepsin B's involvement in constitutive APP processing.
  • Demonstrated cathepsin B cleavage of APP into 115 kDa and 9 kDa fragments.

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Conclusions:

  • Lysosomal cathepsin B is identified as a candidate APP secretase.
  • The cleavage products suggest a role for cathepsin B in normal APP metabolism and potentially AD.