All quiet on the neuronal front: NMDA receptor inhibition by prion protein

J Cell Biol. 2008 May 5;181(3):407-9. doi: 10.1083/jcb.200803152. Epub 2008 Apr 28.

Abstract

The normal function of the prion protein (PrP)-the causative agent of mad cow or prion disease-has long remained out of reach. Deciphering PrP's function may help to unravel the complex chain of events triggered by PrP misfolding during prion disease. In this issue of the JCB, an exciting paper (Khosravani, H., Y. Zhang, S. Tsutsui, S. Hameed, C. Altier, J. Hamid, L. Chen, M. Villemaire, Z. Ali, F.R. Jirik, and G.W. Zamponi. 2008. J. Cell Biol. 181:551-565) connects diverse observations regarding PrP into a coherent framework whereby PrP dampens the activity of an N-methyl-d-aspartate (NMDA) receptor (NMDAR) subtype and reduces excitotoxic lesions. The findings of this study suggest that understanding the normal function of proteins associated with neurodegenerative disease may elucidate the molecular pathogenesis.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Excitatory Amino Acid Agonists / metabolism
  • Humans
  • Mice
  • Mice, Knockout
  • N-Methylaspartate / metabolism
  • Neurons / metabolism*
  • Neurons / pathology
  • Prions / chemistry
  • Prions / genetics
  • Prions / metabolism*
  • Protein Folding
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Excitatory Amino Acid Agonists
  • Prions
  • Protein Subunits
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate