Skip to main content

Amyloid Precursor Protein Processing in Vivo - Insights from a Chemically- Induced Constitutive Overactivation of Protein Kinase C in Guinea Pig Brain

Buy Article:

$55.00 plus tax (Refund Policy)

Aberrant proteolytical processing of the amyloid precursor protein (APP) gives rise to β-amyloid peptides, which form deposits characteristic for the brains of Alzheimer's disease patients. From in vitro studies, protein kinase C (PKC) is known for almost 20 years to be involved the secretory pathway of APP processing, resulting in the reduced generation of β-amyloid peptides. However, the toxicity of activators of PKC, such as phorbol esters, has prevented to test the hypothesis of an inverse regulation of secretory APP processing and β-amyloid generation in vivo. Here we present an animal model which allows to reveal the function of PKC in the proteolytical processing of APP in vivo.

Studies by Johnstone and Coyle from the early 1980s have shown that treatment of pregnant rats with methylazoxymethanol acetate (MAM) results in the induction of neocortical microencephalopathy of the offsprings. Later on, the constitutive overactivation of PKC isoforms was described in affected brain structures of these animals. This led to the idea to study the APP processing under conditions of overactivated PKC in the brains of such animals in vivo. However, in mice and rats one can follow the generation of secretory APP products but the detection of rodent β-amyloid peptides is delicate.

Therefore, we adapted the MAM model to guinea pigs, which have a human β-amyloid sequence, and investigated the relation between secretory APP processing and β-amyloid generation in vivo. In the brains of microencephalic guinea pigs we observed increased levels of secretory APP fragments but no change in the concentration of β-amyloid peptides. Our results indicate that both pathways of APP processing are differentially controlled under these experimental conditions in vivo.

No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: alzheimers disease; amyloid precursor protein; guinea pig; microencephalopathy; protein kinase c; secretases

Document Type: Review Article

Publication date: 2003-05-01

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more