Phosphatidylinositol-glycan-phospholipase D is involved in neurodegeneration in prion disease

PLoS One. 2015 Apr 13;10(4):e0122120. doi: 10.1371/journal.pone.0122120. eCollection 2015.


PrPSc is formed from a normal glycosylphosphatidylinositol (GPI)-anchored prion protein (PrPC) by a posttranslational modification. Most GPI-anchored proteins have been shown to be cleaved by GPI phospholipases. Recently, GPI-phospholipase D (GPI-PLD) was shown to be a strictly specific enzyme for GPI anchors. To investigate the involvement of GPI-PLD in the processes of neurodegeneration in prion diseases, we examined the mRNA and protein expression levels of GPI-PLD in the brains of a prion animal model (scrapie), and in both the brains and cerebrospinal fluids (CSF) of sporadic and familial Creutzfeldt-Jakob disease (CJD) patients. We found that compared with controls, the expression of GPI-PLD was dramatically down-regulated in the brains of scrapie-infected mice, especially in the caveolin-enriched membrane fractions. Interestingly, the observed decrease in GPI-PLD expression levels began at the same time that PrPSc began to accumulate in the infected brains and this decrease was also observed in both the brain and CSF of CJD patients; however, no differences in expression were observed in either the brains or CSF specimens from Alzheimer's disease patients. Taken together, these results suggest that the down-regulation of GPI-PLD protein may be involved in prion propagation in the brains of prion diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Brain / enzymology
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Neurodegenerative Diseases / enzymology
  • Neurodegenerative Diseases / pathology*
  • Phospholipase D / cerebrospinal fluid
  • Phospholipase D / metabolism*
  • Prion Diseases / enzymology
  • Prion Diseases / pathology*


  • Phospholipase D
  • glycoprotein phospholipase D

Grant support

The present study was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2008-313-E00110, KRF-2011-619-E0001).