Human anti-prion antibodies block prion peptide fibril formation and neurotoxicity

Xing Wei, Yvonne Roettger, Bailin Tan, Yongzheng He, Richard Dodel, Harald Hampel, Gang Wei, Jillian Haney, Huiying Gu, Brian H. Johnstone, Junyi Liu, Martin R. Farlow, Yansheng Du

Research output: Contribution to journalArticle

16 Scopus citations


Prion diseases are a group of rare, fatal neurodegenerative disorders associated with a conformational transformation of the cellular prion protein (PrP C) into a self-replicating and proteinase K-resistant conformer, termed scrapie PrP (PrP Sc). Aggregates of PrP Sc deposited around neurons lead to neuropathological alterations. Currently, there is no effective treatment for these fatal illnesses; thus, the development of an effective therapy is a priority. PrP peptide-based ELISA assay methods were developed for detection and immunoaffinity chromatography capture was developed for purification of naturally occurring PrP peptide autoantibodies present in human CSF, individual donor serum, and commercial preparations of pooled intravenous immunoglobulin (IVIg). The ratio of anti- PrP autoantibodies (PrP-AA) to total IgG was ∼1:1200. The binding epitope of purified PrP-AA was mapped to an N-terminal region comprising the PrP amino acid sequence KTNMK. Purified PrP-AA potently blocked fibril formation by a toxic 21-amino acid fragment of the PrP peptide containing the amino acid alanine to valine substitution corresponding to position 117 of the full-length peptide (A117V). Furthermore, PrP-AA attenuated the neurotoxicity of PrP(A117V) and wildtype peptides in rat cerebellar granule neuron (CGN) cultures. In contrast, IgG preparations depleted of PrP-AA had little effect on PrP fibril formation or PrP neurotoxicity. The specificity of PrP-AA was demonstrated by immunoprecipitating PrP protein in brain tissues of transgenic mice expressing the human PrP(A117V) epitope and Sc237 hamster. Based on these intriguing findings, it is suggested that human PrP-AA may be useful for interfering with the pathogenic effects of pathogenic prion proteins and, thereby has the potential to be an effective means for preventing or attenuating human prion disease progression.

Original languageEnglish (US)
Pages (from-to)12858-12866
Number of pages9
JournalJournal of Biological Chemistry
Issue number16
StatePublished - Apr 13 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Human anti-prion antibodies block prion peptide fibril formation and neurotoxicity'. Together they form a unique fingerprint.

  • Cite this

    Wei, X., Roettger, Y., Tan, B., He, Y., Dodel, R., Hampel, H., Wei, G., Haney, J., Gu, H., Johnstone, B. H., Liu, J., Farlow, M. R., & Du, Y. (2012). Human anti-prion antibodies block prion peptide fibril formation and neurotoxicity. Journal of Biological Chemistry, 287(16), 12858-12866.