Journal of Molecular Neuroscience

, Volume 51, Issue 3, pp 655–662

Using Protein Misfolding Cyclic Amplification Generates a Highly Neurotoxic PrP Dimer Causing Neurodegeneration

  • XiuJin Yang
  • LiFeng Yang
  • XiangMei Zhou
  • Sher Hayat Khan
  • HuiNuan Wang
  • XiaoMin Yin
  • Zhen Yuan
  • ZhiQi Song
  • WenYu Wu
  • DeMing Zhao
Article

DOI: 10.1007/s12031-013-0039-z

Cite this article as:
Yang, X., Yang, L., Zhou, X. et al. J Mol Neurosci (2013) 51: 655. doi:10.1007/s12031-013-0039-z

Abstract

Under the “protein-only” hypothesis, prion-based diseases are proposed to result from an infectious agent that is an abnormal isoform of the prion protein in the scrapie form, PrPSc. However, since PrPSc is highly insoluble and easily aggregates in vivo, this view appears to be overly simplistic, implying that the presence of PrPSc may indirectly cause neurodegeneration through its intermediate soluble form. We generated a neurotoxic PrP dimer with partial pathogenic characteristics of PrPSc by protein misfolding cyclic amplification in the presence of 1-palmitoyl-2-oleoylphosphatidylglycerol consisting of recombinant hamster PrP (23–231). After intracerebral injection of the PrP dimer, wild-type hamsters developed signs of neurodegeneration. Clinical symptoms, necropsy findings, and histopathological changes were very similar to those of transmissible spongiform encephalopathies. Additional investigation showed that the toxicity is primarily related to cellular apoptosis. All results suggested that we generated a new neurotoxic form of PrP, PrP dimer, which can cause neurodegeneration. Thus, our study introduces a useful model for investigating PrP-linked neurodegenerative mechanisms.

Keywords

PrionPrP dimerPMCAPrPScPrP

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • XiuJin Yang
    • 1
  • LiFeng Yang
    • 1
  • XiangMei Zhou
    • 1
  • Sher Hayat Khan
    • 1
  • HuiNuan Wang
    • 1
  • XiaoMin Yin
    • 1
  • Zhen Yuan
    • 1
  • ZhiQi Song
    • 1
  • WenYu Wu
    • 1
  • DeMing Zhao
    • 1
  1. 1.State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy LaboratoryCollege of Veterinary Medicine, China Agricultural UniversityBeijingChina