Display options
Cite
West E, Osborne C, Nolan W, et al. Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage. Biology (Basel). 2015;4(2):367-82doi: 10.3390/biology4020367.
West, E., Osborne, C., Nolan, W., & Bate, C. (2015). Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage. Biology, 4(2), 367-82. https://doi.org/10.3390/biology4020367
West, Ewan, et al. "Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage." Biology vol. 4,2 (2015): 367-82. doi: https://doi.org/10.3390/biology4020367
West E, Osborne C, Nolan W, Bate C. Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage. Biology (Basel). 2015 Jun 02;4(2):367-82. doi: 10.3390/biology4020367. PMID: 26043272; PMCID: PMC4498305.
Copy Download .nbib Format: NLM
Share it on

Biology (Basel). 2015 Jun 02;4(2):367-82. doi: 10.3390/biology4020367.

Monoacylated Cellular Prion Proteins Reduce Amyloid-β-Induced Activation of Cytoplasmic Phospholipase A2 and Synapse Damage.

Biology

Ewan West, Craig Osborne, William Nolan, Clive Bate

Affiliations

  1. Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts AL97TA, UK. [email protected].
  2. Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts AL97TA, UK. [email protected].
  3. Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts AL97TA, UK. [email protected].
  4. Department of Pathology and Pathogen Biology, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts AL97TA, UK. [email protected].

PMID: 26043272 PMCID: PMC4498305 DOI: 10.3390/biology4020367

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ) and the loss of synapses. Aggregation of the cellular prion protein (PrPC) by Aβ oligomers induced synapse damage in cultured neurons. PrPC is attached to membranes via a glycosylphosphatidylinositol (GPI) anchor, the composition of which affects protein targeting and cell signaling. Monoacylated PrPC incorporated into neurons bound "natural Aβ", sequestering Aβ outside lipid rafts and preventing its accumulation at synapses. The presence of monoacylated PrPC reduced the Aβ-induced activation of cytoplasmic phospholipase A2 (cPLA2) and Aβ-induced synapse damage. This protective effect was stimulus specific, as treated neurons remained sensitive to α-synuclein, a protein associated with synapse damage in Parkinson's disease. In synaptosomes, the aggregation of PrPC by Aβ oligomers triggered the formation of a signaling complex containing the cPLA2.a process, disrupted by monoacylated PrPC. We propose that monoacylated PrPC acts as a molecular sponge, binding Aβ oligomers at the neuronal perikarya without activating cPLA2 or triggering synapse damage.

Keywords: Alzheimer’s disease; amyloid-β; glycosylphosphatidylinositols; prion; synapses; synaptophysin

References

  1. J Biol Chem. 2011 Nov 4;286(44):37955-63 - PubMed
  2. Science. 2005 Jun 3;308(5727):1435-9 - PubMed
  3. J Neurochem. 2007 Jun;101(5):1172-84 - PubMed
  4. J Biol Chem. 1993 Jul 25;268(21):15922-8 - PubMed
  5. Proc Natl Acad Sci U S A. 1998 May 26;95(11):6448-53 - PubMed
  6. Science. 2002 Jul 19;297(5580):353-6 - PubMed
  7. Biochem J. 2004 Mar 1;378(Pt 2):281-92 - PubMed
  8. J Biol Chem. 2002 Dec 6;277(49):47671-8 - PubMed
  9. Neuropharmacology. 2007 Aug;53(2):222-31 - PubMed
  10. FASEB J. 2001 Feb;15(2):545-8 - PubMed
  11. Am J Pathol. 2001 Jun;158(6):2209-18 - PubMed
  12. J Biol Chem. 2011 Mar 18;286(11):8752-8 - PubMed
  13. J Alzheimers Dis. 2005 Apr;7(2):103-17; discussion 173-80 - PubMed
  14. Science. 2002 Oct 25;298(5594):789-91 - PubMed
  15. J Neurosci. 1999 Oct 15;19(20):8866-75 - PubMed
  16. Nature. 2009 Feb 26;457(7233):1128-32 - PubMed
  17. J Neurosci. 2007 Feb 7;27(6):1405-10 - PubMed
  18. Mol Neurodegener. 2010 Dec 07;5:55 - PubMed
  19. J Biol Chem. 1995 Apr 21;270(16):9564-70 - PubMed
  20. J Biol Chem. 1994 Jul 8;269(27):18239-49 - PubMed
  21. EMBO Mol Med. 2010 Aug;2(8):306-14 - PubMed
  22. J Neurochem. 2008 Jul;106(1):45-55 - PubMed
  23. Nat Neurosci. 2000 May;3(5):460-4 - PubMed
  24. Neuron. 2010 Jun 10;66(5):739-54 - PubMed
  25. Trends Neurosci. 2001 Apr;24(4):219-24 - PubMed
  26. J Neurosci. 2009 Aug 26;29(34):10627-37 - PubMed
  27. Biochemistry. 1992 Jun 2;31(21):5043-53 - PubMed
  28. J Biol Chem. 2012 Mar 9;287(11):7935-44 - PubMed
  29. J Cell Biol. 1995 Apr;129(1):121-32 - PubMed
  30. Mol Neurodegener. 2010 Apr 08;5:13 - PubMed
  31. J Biol Chem. 2008 Oct 31;283(44):29639-43 - PubMed
  32. Biochim Biophys Acta. 2000 Nov 23;1508(1-2):182-95 - PubMed
  33. Am J Pathol. 1991 Jan;138(1):235-46 - PubMed
  34. Nature. 1996 Aug 22;382(6593):685-91 - PubMed
  35. J Cell Biol. 2001 Apr 30;153(3):529-41 - PubMed
  36. Science. 2004 Mar 5;303(5663):1514-6 - PubMed
  37. Science. 2010 Jan 1;327(5961):46-50 - PubMed
  38. J Biol Chem. 2004 Jan 2;279(1):356-62 - PubMed
  39. Arch Neurol. 2001 Aug;58(8):1233-9 - PubMed
  40. J Virol. 1989 Jan;63(1):175-81 - PubMed
  41. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6120-5 - PubMed

Publication Types