Related Experiment Video

Updated: Oct 7, 2026

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase
11:57

Saccharomyces cerevisiae Models of Alzheimer's Disease to Screen Genes, Mutations, and Chemicals Affecting Amyloid Beta Production by γ-Secretase

Published on: June 24, 2025

Protein kinase Calpha and beta1 isoforms are regulators of alpha-secretory proteolytic processing of amyloid

S Rossner1, K Mendla, R Schliebs

  • 1Department of Neurochemistry, Paul Flechsig Institute for Brain Research, Jahnallee 59, 04109 Leipzig, Germany. rossn@medizin.uni-leipzig.de

The European Journal of Neuroscience
|May 1, 2001
PubMed

Insights

In utero exposure to methylazoxymethanol acetate (MAM) causes brain abnormalities and alters amyloid precursor protein (APP) processing. PKCalpha and PKCbeta1 are key regulators of non-amyloidogenic APP processing in affected guinea pigs.

Area of Science:

  • Neuroscience
  • Developmental Neuroscience
  • Molecular Biology

Background:

  • In utero exposure to methylazoxymethanol acetate (MAM) induces neocortical microencephalopathy in guinea pigs.
  • This exposure alters amyloid precursor protein (APP) processing and increases protein kinase C (PKC) activity in the offspring's neocortex.

Purpose of the Study:

  • To identify the specific protein kinase C (PKC) isoforms regulating alpha-secretory APP processing in MAM-induced neocortical microencephalopathy.
  • To investigate the role of PKCalpha and PKCbeta1 in non-amyloidogenic APP processing in vivo.

Main Methods:

  • Western blot analysis and immunocytochemistry to detect PKC isoform translocation.
  • Measurement of [3H]phorbol ester binding to assess PKC activity.
  • Pharmacological inhibition of PKCalpha/PKCbeta1 using Gö6976.
  • Correlation analysis between APP processing and PKC activity.

Main Results:

  • Selective translocation of PKCalpha and PKCbeta1 to the cell membrane in MAM-treated guinea pigs.
  • Significant increase in [3H]phorbol ester binding and basal PKC activity in microencephalic neocortex.
  • Inhibition of PKCalpha/PKCbeta1 abolished the observed increase in PKC activity.
  • Strong positive correlation between alpha-secretase-processed APP levels and PKC activity.

Conclusions:

  • PKCalpha and PKCbeta1 are the primary regulators of alpha-secretory APP processing in MAM-induced neocortical microencephalopathy.
  • Constitutive overactivation of PKCalpha and PKCbeta1 contributes to increased total PKC activity.
  • Classical PKC isoforms play a significant role in non-amyloidogenic APP processing in this model.

More Related Videos

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays09:36

Recombinant α- β- and γ-Synucleins Stimulate Protein Phosphatase 2A Catalytic Subunit Activity in Cell Free Assays

Published on: August 13, 2017

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain10:08

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain

Published on: August 28, 2012

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...