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Related Experiment Videos

Receptor-coupled amyloid precursor protein processing

R M Nitsch1, B E Slack, S A Farber

  • 1Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.

Annals of the New York Academy of Sciences
|September 24, 1993
PubMed
Summary
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Cell surface receptors and neuronal activity regulate amyloid precursor protein (APP) processing. Muscarinic acetylcholine receptors (mAChR) and bradykinin stimulation increase APP fragment release, suggesting neuronal activity influences APP processing in the brain.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Amyloid precursor protein (APP) processing involves multiple pathways, some generating amyloidogenic fragments.
  • Understanding cellular mechanisms regulating APP processing is crucial for Alzheimer's disease research.
  • Cell-surface receptor activity's role in APP processing remains to be fully elucidated.

Purpose of the Study:

  • To investigate if cell-surface receptor activity regulates APP processing.
  • To determine the role of neuronal activity in APP processing within the mammalian brain.

Main Methods:

  • HEK 293 cell lines expressing different muscarinic acetylcholine receptor (mAChR) subtypes were stimulated with carbachol.
  • Differentiated PC-12 cells were stimulated with bradykinin.

Related Experiment Videos

  • Electrically stimulated rat hippocampal slices were used to assess APP derivative release.

    • Main Results:

    • Carbachol increased amino-terminal APP fragment release 4-6 fold in m1 and m3 mAChR expressing cells, mediated by protein kinase C (PKC).
    • Bradykinin stimulation also increased amino-terminal APP derivative secretion.
    • Electrically stimulated hippocampal slices released twice as many amino-terminal APP derivatives, with release increasing with stimulation frequency.

    Conclusions:

    • Cell-surface receptors, specifically m1 and m3 mAChRs, can regulate APP processing.
    • Neuronal activity, through depolarization, significantly impacts APP processing in the brain.
    • These findings suggest a link between neuronal activity and the generation of APP derivatives.