Related Experiment Video

Updated: Oct 2, 2026

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
12:57

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans

Published on: January 8, 2015

Cellular phenotyping of secretory and nuclear prion proteins associated with inherited prion diseases

Holger Lorenz1, Otto Windl, Hans A Kretzschmar

  • 1Institut für Neuropathologie, Ludwig-Maximilians-Universität München, D-81377 München, Germany.

The Journal of Biological Chemistry
|January 5, 2002
PubMed

Insights

Mutant prion protein (PrP) processing may cause infectious prion diseases. Aberrant cellular pathways for PrP mutants, like those in Creutzfeldt-Jakob disease, contribute to disease pathogenesis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Pathogenic mechanisms of prion protein (PrP) gene mutations remain unclear.
  • Investigating cellular processing of mutant PrP for infectious particle formation is crucial.

Purpose of the Study:

  • To explore how cellular processing of mutant prion protein contributes to prion disease pathogenesis.
  • To examine novel PrP mutants using a mouse PrP model.

Main Methods:

  • Established a mouse PrP model using green fluorescent protein.
  • Examined three novel PrP mutants, comparing them to wild-type and known mutants.
  • Assessed PrP localization, proteinase K resistance, and detergent insolubility.

Main Results:

  • Two Creutzfeldt-Jakob disease-associated mutants (PrP T188K, PrP T188R) showed secretory pathway localization and PrP(Sc)-like properties.
  • A truncated PrP mutant (PrP Q160(Stop)) localized to the nucleus and was degraded via the proteasomal pathway.
  • Mutant PrPs exhibited enhanced proteinase K resistance and detergent insolubility.

Conclusions:

  • Distinct pathological mechanisms likely underlie prion diseases.
  • Aberrant cellular processing of prion protein is implicated in prion disease pathogenesis.

More Related Videos

High-throughput Screening for Protein-based Inheritance in S. cerevisiae08:12

High-throughput Screening for Protein-based Inheritance in S. cerevisiae

Published on: August 8, 2017

Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster10:26

Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster

Published on: March 12, 2018

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Subviral Agents01:29

Subviral Agents

Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...