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Updated: Jun 3, 2026
Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Differential targeting of neurons by prion strains
1Department of Pathology (Neuropathology), University of California, San Francisco, CA.
Abstract:
A basic principle of microbiology that applies to all conventional infectious pathogens is that the disease phenotype is a function of both the infecting agent and the host's response to it. All evidence indicates that this principle is also true for diseases acquired by infection with prions, given that inoculation of different scrapie prion strains into inbred mouse strains shows that reproducible differences in the disease phenotype are determined by both the strain of scrapie prion and a host gene or genes (1-6). The disease parameters used to characterize and define each prion strain, then and now, include: the relative or complete failure of transmission of a prion strain from one animal species to another, designated the "host species barrier"; incubation time, defined as the time from inoculation of a prion strain to the onset of clinical signs; the neuroanatomic distribution of spongiform degeneration, also designated the "lesion profile"; and whether or not PrP amyloid plaques are formed in the brain. Of these parameters, least is known about how each prion strain targets a different population of neurons for degeneration to create the strain-specific lesion profile. The goal of this report is to review the evidence, which argues that PrP(Sc) is the main and perhaps sole prion factor determining the disease phenotype, and that PrP(C) expressed by the host animal is the predominant host factor determining the disease phenotype, including differential targeting of neurons.
Insights
Prion diseases are influenced by both the infectious prion strain and the host
Area of Science:
- Neuroscience
- Microbiology
- Genetics
Background:
- The disease phenotype of infectious agents is determined by both the agent and the host's response.
- This principle extends to prion diseases, where disease characteristics depend on the prion strain and host genetics.
- Key prion disease parameters include host species barrier, incubation time, lesion profile, and plaque formation.
Purpose of the Study:
- To review evidence on how prion strains target neuronal populations.
- To elucidate the roles of PrP(Sc) and PrP(C) in determining prion disease phenotypes.
- To understand the host's role in differential neuronal targeting in prion diseases.
Main Methods:
- Review of existing scientific literature and experimental evidence.
- Analysis of prion strain characteristics and host genetic influences.
- Examination of neuroanatomical and biochemical data related to prion infections.
Main Results:
- Prion protein scrapie (PrP(Sc)) is identified as the primary prion factor influencing disease phenotype.
- Host prion protein cellular (PrP(C)) is the predominant host factor determining disease phenotype.
- Evidence suggests PrP(C) plays a crucial role in the differential targeting of neurons by prion strains.
Conclusions:
- The disease phenotype in prion infections is a complex interplay between the prion agent and host factors.
- PrP(Sc) and host PrP(C) are critical determinants of prion disease characteristics, including lesion profiles.
- Understanding these interactions is key to deciphering the mechanisms underlying prion disease pathogenesis.
