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Rapid Generation of Amyloid from Native Proteins In vitro
05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 5, 2013

A novel mechanism for the regulation of amyloid precursor protein metabolism

Qi Chen1, Hideo Kimura, David Schubert

  • 1Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

The Journal of Cell Biology
|July 3, 2002
PubMed

Insights

Modifier of cell adhesion protein (MOCA) reduces amyloid precursor protein (APP) secretion and cell adhesion by targeting APP for proteasomal degradation. This discovery reveals a novel mechanism regulating APP expression, potentially impacting Alzheimer's disease (AD) pathology.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Modifier of cell adhesion protein (MOCA) interacts with presenilin (PS) proteins, implicated in Alzheimer's disease (AD).
  • MOCA is localized to AD-affected brain regions and reduced in sporadic AD brains.
  • PS1's association with gamma-secretase suggests MOCA's role in beta-amyloid precursor protein (APP) processing.

Purpose of the Study:

  • To investigate the role of MOCA in APP processing and cell adhesion.
  • To elucidate the mechanism by which MOCA affects APP secretion and cellular behavior.

Main Methods:

  • Assessed the impact of MOCA expression on APP and amyloid beta-peptide secretion.
  • Measured cell-substratum adhesion rates.
  • Investigated the effect of MOCA on amyloid precursor-like protein (APLP) secretion.
  • Utilized proteasome inhibitors to explore the degradation pathway of APP.

Main Results:

  • MOCA expression decreased both APP and amyloid beta-peptide secretion.
  • MOCA reduced cell-substratum adhesion rates.
  • MOCA did not affect the secretion of APLP or other type 1 membrane proteins.
  • Phenotypic changes were attributed to accelerated intracellular APP degradation via proteasomes.
  • Proteasome inhibitors reversed MOCA's effects on APP secretion and cell adhesion.

Conclusions:

  • MOCA plays a significant role in APP metabolism.
  • MOCA directs nascent APP to proteasomes for degradation, a novel regulatory mechanism.
  • MOCA's effects on APP secretion and cell adhesion are downstream consequences of APP catabolism.
  • This mechanism offers new insights into APP expression regulation and potential AD therapeutic targets.

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