Nonenzymatic glycation at the N terminus of pathogenic prion protein in transmissible spongiform encephalopathies.

  • Choi Y
  • Kim J
  • Jeon Y
 et al. 
  • 6

    Readers

    Mendeley users who have this article in their library.
  • N/A

    Citations

    Citations of this article.

Abstract

Transmissible spongiform encephalopathies (TSEs) are transmissible neurodegenerative diseases characterized by the accumulation of an abnormally folded prion protein, termed PrPSc, and the development of pathological features of astrogliosis, vacuolation, neuronal cell loss, and in some cases amyloid plaques. Although considerable structural characterization of prion protein has been reported, neither the method of conversion of cellular prion protein, PrPC, into the pathogenic isoform nor the post-translational modification processes involved is known. We report that in animal and human TSEs, one or more lysines at residues 23, 24, and 27 of PrPSc are covalently modified with advanced glycosylation end products (AGEs), which may be carboxymethyl-lysine (CML), one of the structural varieties of AGEs. The arginine residue at position 37 may also be modified with AGE, but not the arginine residue at position 25. This result suggests that nonenzymatic glycation is one of the post-translational modifications of PrP(Sc). Furthermore, immunostaining studies indicate that, at least in clinically affected hamsters, astrocytes are the first site of this glycation process.

Author-supplied keywords

  • Animals
  • Arginine
  • Arginine: chemistry
  • Astrocytes
  • Binding, Competitive
  • Blotting, Western
  • Brain
  • Brain: metabolism
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Glycosylation
  • Humans
  • Immunohistochemistry
  • Kinetics
  • Lysine
  • Lysine: analogs & derivatives
  • Lysine: chemistry
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Oxygen
  • Oxygen: metabolism
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine
  • Peptides
  • Peptides: chemistry
  • PrPSc Proteins
  • PrPSc Proteins: chemistry
  • Precipitin Tests
  • Prion Diseases
  • Prion Diseases: metabolism
  • Prions
  • Prions: chemistry
  • Protein Isoforms
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Yeong-Gon Choi

  • Jae-Il Kim

  • Yong-Chul Jeon

  • Seok-Joo Park

  • Eun-Kyoung Choi

  • Richard Rubenstein

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free