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Silent prions lying in wait: a two-hit model of prion/amyloid formation and infection

Damien Hall1, Herman Edskes

  • 1Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health Bethesda, MD 20892-0830, USA. drh32@cam.ac.uk

Journal of Molecular Biology
|April 21, 2004
PubMed

Insights

Amyloid and prion diseases may initiate due to a combination of protein presence and host state changes. This model suggests infectious amyloids could lie dormant, similar to cancer progression, and may be characterized by size distribution.

Area of Science:

  • Biophysics
  • Neurodegenerative Diseases
  • Molecular Biology

Background:

  • Amyloid formation is linked to diseases like Alzheimer's, Parkinson's, and type 2 diabetes.
  • Transmissible spongiform encephalopathies are caused by infectious amyloid proteins known as prions.
  • The spontaneous initiation and host-to-host transmission of amyloid/prions remain incompletely understood.

Purpose of the Study:

  • To explore a mathematical model for amyloid/prion initiation and propagation.
  • To investigate the role of host state changes in amyloid/prion pathogenesis.
  • To draw parallels between prion/amyloid diseases and the two-hit model of cancer progression.

Main Methods:

  • Development of a mathematical model to simulate amyloid/prion dynamics.
  • Analysis of the interplay between prion/amyloid presence and host susceptibility.
  • Comparison of disease initiation mechanisms with established models like the two-hit hypothesis for cancer.

Main Results:

  • The model suggests that amyloid/prion initiation and propagation depend on both the presence of the infectious agent and a favorable host state.
  • A hypothesis is proposed that infectious amyloids may remain dormant in healthy individuals until triggered by host changes or transmission.
  • Infectious amyloid strains might be distinguishable by their size distribution (length or radius).

Conclusions:

  • A combined factor of amyloid/prion presence and host state change is proposed as a mechanism for disease initiation.
  • The findings suggest a potential for dormant infectious amyloid in apparently healthy individuals.
  • The study introduces the possibility of characterizing infectious amyloid strains by their physical dimensions, drawing an analogy to cancer progression models.

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