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Updated: Nov 28, 2025

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain
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Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain

Published on: October 3, 2012

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Met166 -Glu168 residues in human PrP β2-α2 loop account for evolutionary resistance to prion infection

Juan Carlos Espinosa1, Alba Marín-Moreno1, Patricia Aguilar-Calvo1

  • 1Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain.

Neuropathology and Applied Neurobiology
|November 30, 2020
PubMed
Abstract

Insights

Human prion protein (PrP) sequence variations influence prion disease transmissibility. Specific amino acid changes in human PrP limit the spread of most prion strains, impacting prion disease research.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Prion Disease Research

Background:

  • Prion diseases are fatal neurodegenerative disorders linked to misfolded prion proteins (PrP).
  • The amino acid sequence of PrP is crucial for prion disease transmissibility, with minor variations potentially altering susceptibility across species.
  • While bovine spongiform encephalopathy (BSE) is zoonotic, the factors limiting human transmission of other prion strains like scrapie and chronic wasting disease (CWD) remain unclear.

Purpose of the Study:

  • To investigate the role of specific human PrP amino acid residues in limiting prion strain transmissibility.
  • To compare prion disease propagation in transgenic mice expressing wild-type human PrP versus a mutated form.

Main Methods:

  • Transgenic mice expressing either wild-type human PrP (MDE-HuTg340) or a mutated human PrP with Val166-Gln168 substitutions (VDQ-HuTg372) were generated.
  • These mice were inoculated with a panel of diverse prion strains from different species to assess transmissibility.

Main Results:

  • Transgenic mice with the mutated human PrP (VDQ-HuTg372) exhibited increased susceptibility to prion infections compared to those with wild-type human PrP (MDE-HuTg340).
  • This heightened susceptibility was observed in a prion strain-dependent manner.

Conclusions:

  • The Met166-Glu168 amino acid residues in wild-type human PrP act as molecular determinants that restrict the propagation of most prion strains within the human PrP context.
  • These findings highlight specific sequence elements in human PrP that confer resistance to prion infection, offering insights into interspecies prion transmission barriers.
Keywords:
PrPevolutionprionresistancestrain

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