Advertisement

Shortening heparan sulfate chains prolongs survival and reduces parenchymal plaques in prion disease caused by mobile, ADAM10-cleaved prions

  • Patricia Aguilar-Calvo
  • Alejandro M. Sevillano
  • Jaidev Bapat
  • Katrin Soldau
  • Daniel R. Sandoval
  • Hermann C. Altmeppen
  • Luise Linsenmeier
  • Donald P. Pizzo
  • Michael D. Geschwind
  • Henry Sanchez
  • Brian S. Appleby
  • Mark L. Cohen
  • Jiri G. Safar
  • Steven D. Edland
  • Markus Glatzel
  • K. Peter R. Nilsson
  • Jeffrey D. Esko
  • Christina J. SigurdsonEmail author
Original Paper

Abstract

Cofactors are essential for driving recombinant prion protein into pathogenic conformers. Polyanions promote prion aggregation in vitro, yet the cofactors that modulate prion assembly in vivo remain largely unknown. Here we report that the endogenous glycosaminoglycan, heparan sulfate (HS), impacts prion propagation kinetics and deposition sites in the brain. Exostosin-1 haploinsufficient (Ext1+/) mice, which produce short HS chains, show a prolonged survival and a redistribution of plaques from the parenchyma to vessels when infected with fibrillar prions, and a modest delay when infected with subfibrillar prions. Notably, the fibrillar, plaque-forming prions are composed of ADAM10-cleaved prion protein lacking a glycosylphosphatidylinositol anchor, indicating that these prions are mobile and assemble extracellularly. By analyzing the prion-bound HS using liquid chromatography–mass spectrometry (LC–MS), we identified the disaccharide signature of HS differentially bound to fibrillar compared to subfibrillar prions, and found approximately 20-fold more HS bound to the fibrils. Finally, LC–MS of prion-bound HS from human patients with familial and sporadic prion disease also showed distinct HS signatures and higher HS levels associated with fibrillar prions. This study provides the first in vivo evidence of an endogenous cofactor that accelerates prion disease progression and enhances parenchymal deposition of ADAM10-cleaved, mobile prions.

Keywords

Amyloid Neurodegeneration Glycosaminoglycans ADAM10 cleavage 

Notes

Acknowledgements

We thank Chrissa Dwyer and Jessica Lawrence for discussions, Biswa Choudhury, Nazilla Alderson, and Jin Wang for outstanding technical support, and the animal care staff at UC San Diego for excellent animal care. We also thank the UC San Diego GlycoAnalytics Core for the mass spectrometry analysis. The authors are grateful to the patients’ families, the CJD Foundation, referring clinicians, and all the members of the National Prion Disease Pathology Surveillance Center for invaluable technical help. This study was supported by the National Institutes of Health grants NS069566 (CJS), NS076896 (CJS), NS103848 (JGS), AG031189 (MDG), AG061251 (PAC), IL1 TR001442 (SDE) the U.S. Centers for Disease Control and Prevention (BSA), the CJD Foundation (CJS and HCA), the Werner-Otto-Stiftung (HCA) the Michael J. Homer Family Fund (MDG), and the Ramón Areces Foundation (PAC).

Author contributions

PAC, KPRN, CJS, DRS, and JDE designed experiments, PAC, AMS, JB, KS, DPP, and KPRN performed the experiments, PAC, JB, LL, HCA, SDE, MG, JGS, KPRN, JDE, CJS, MLC, and BSA analyzed experiments, MDG and HS provided sCJD cases, and PAC and CJS wrote the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have declared that no conflict of interest exists.

Supplementary material

401_2019_2085_MOESM1_ESM.pdf (13 kb)
Bound to PrPSc (PDF 13 kb)
401_2019_2085_MOESM2_ESM.docx (15 kb)
Supplementary material 2 (DOCX 16 kb)
401_2019_2085_MOESM3_ESM.pdf (913 kb)
Online resource 1 Shortening heparan sulfate chains does not alter PrPC expression. a Western blot shows PrPC in brain homogenate of age-matched Ext1+/+ versus Ext1+/- mice and tga20+/-Ext1+/+ versus tga20+/-Ext1+/- mice (n=3/group) (anti-PrP antibody: POM19). b Quantification of PrPC levels relative to actin
401_2019_2085_MOESM4_ESM.pdf (843 kb)
Online resource 2 Shortening heparan sulfate chains does not impact the levels of PrPSc in brain. a Western blot shows PrPSc in brain homogenate of Ext1+/+ versus Ext1+/- mice (anti-PrP antibody: POM19). b Quantification of PrPSc levels (n=4-6/group)
401_2019_2085_MOESM5_ESM.pdf (785 kb)
Online resource 3 Immunolabeling for PrP and Alcian blue staining for acidic polysaccharides in the brain of prion-infected mice. Subfibrillar prions 22L, RML, and ME7 do not bind detectable levels of Alcian blue, while fibrillar prions mCWD and GPI- RML bind abundant Alcian blue, indicating the presence of acidic polysaccharides, such as GAGs. Shown is hippocampus (22L, RML, ME7, and GPI- RML) and corpus callosum (mCWD). Scale bar = 100 μm for 22L, RML, ME7, and mCWD, and 200 μm for GPI- RML
401_2019_2085_MOESM6_ESM.pdf (161 kb)
Online resource 4 mCWD plaque distribution in tga20+/-Ext1+/- and tga20+/-Ext1+/- mouse brains. aTga20+/-Ext1+/+ (Ext1+/+) and tga20+/-Ext1+/- (Ext1+/-) mice show similar plaque distribution in hippocampus (HP), thalamus (TH), hypothalamus (HT), basal ganglia (BG) and cortex (CX). bExt1+/- mice with survival times longer than 260 dpi (filled bars) show more plaques in the hippocampus and thalamus than the Ext1+/- mice with the shorter survival times (white bars) (n=10-13 mice/group). **P< 0.01 and ***P< 0.001, Fisher’s exact test
401_2019_2085_MOESM7_ESM.pdf (820 kb)
Online resource 5 PrPSc from the 22L-infected brain is composed of primarily GPI-anchored PrP and low levels of shed PrP. a Immunoblots of brain from mCWD- and 22L-infected mice labeled with POM19 antibody (discontinuous epitope at C-terminal domain, amino acids 201–225 of the mouse PrP) or sPrPG228 antibody (binds shed PrP) reveal low levels of sPrPG228 binding to 22L prions as compared to mCWD prions. b Ratios of ADAM10-cleaved PrPSc relative to total PrPSc reveal significantly lower levels of cleaved PrPSc in the 22L-infected brain as compared to mCWD-infected brain (more than 20-fold lower) [22L: 28 ± 18 (n=14) and mCWD: 630 ± 919 (n=5) (mean ± SE)]. *P< 0.05, Wilcoxon rank sum test (panel b)
401_2019_2085_MOESM8_ESM.pdf (541 kb)
Online resource 6 Silver staining of purified PrPSc for HS analysis
401_2019_2085_MOESM9_ESM.pdf (2.9 mb)
Online resource 7 Representative images of the brain histopathology from the human GSS and sCJD cases. GSS-F198S case: Frontal cortex sections immunolabeled for PrP reveal multicentric plaques. The HE stained section shows a little to no spongiform change. GSS-P102L case: Frontal cortex shows synaptic PrP deposits with fine, full-thickness spongiform degeneration (HE). sCJD cases: Brain at thalamus shows highly variable lesions associated with differences in the PRNP genotype at polymorphic codon 129. The sCJD 129 MM1 case shows diffuse or “synaptic” PrP deposits and intense fine vacuoles. The sCJD 129 MV2 case shows plaque-like deposits and vacuolar change, and the sCJD 129 VV2 case shows small plaques and moderate vacuolation. Inset shows MV2 and VV2 plaques from a different field at high magnification. Scale bars = 100 μm (GSS-F198S and sCJD), 10 μm (GSS-P102L) and 50 μm (insets)

References

  1. 1.
    Adjou KT, Simoneau S, Sales N, Lamoury F, Dormont D, Papy-Garcia D et al (2003) A novel generation of heparan sulfate mimetics for the treatment of prion diseases. J Gen Virol 84:2595–2603PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Aguilar-Calvo P, Bett C, Sevillano AM, Kurt TD, Lawrence J, Soldau K et al (2018) Generation of novel neuroinvasive prions following intravenous challenge. Brain Pathol 28:999–1011.  https://doi.org/10.1111/bpa.12598 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Aguilar-Calvo P, Xiao X, Bett C, Erana H, Soldau K et al (2017) Post-translational modifications in PrP expand the conformational diversity of prions in vivo. Sci Rep 7:43295.  https://doi.org/10.1038/srep43295 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Altmeppen HC, Prox J, Krasemann S, Puig B, Kruszewski K, Dohler F, Bernreuther C et al (2015) The sheddase ADAM10 is a potent modulator of prion disease. eLife.  https://doi.org/10.7554/elife.04260 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Ancsin JB (2003) Amyloidogenesis: historical and modern observations point to heparan sulfate proteoglycans as a major culprit. Amyloid 10:67–79PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Bazar E, Jelinek R (2010) Divergent heparin-induced fibrillation pathways of a prion amyloidogenic determinant. ChemBioChem 11:1997–2002.  https://doi.org/10.1002/cbic.201000207 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ben-Zaken O, Tzaban S, Tal Y, Horonchik L, Esko JD, Vlodavsky I et al (2003) Cellular heparan sulfate participates in the metabolism of prions. J Biol Chem 278:40041–40049.  https://doi.org/10.1074/jbc.M301152200 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Beringue V, Le Dur A, Tixador P, Reine F, Lepourry L, Perret-Liaudet A et al (2008) Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. PLoS One 3:e1419.  https://doi.org/10.1371/journal.pone.0001419 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bessen RA, Kocisko DA, Raymond GJ, Nandan S, Lansbury PT, Caughey B (1995) Non-genetic propagation of strain-specific properties of scrapie prion protein. Nature 375:698–700PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Bett C, Fernandez-Borges N, Kurt TD, Lucero M, Nilsson KP, Castilla J et al (2012) Structure of the beta2-alpha2 loop and interspecies prion transmission. FASEB J 26:2868–2876.  https://doi.org/10.1096/fj.11-200923 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bett C, Kurt TD, Lucero M, Trejo M, Rozemuller AJ, Kong Q et al (2013) Defining the conformational features of anchorless, poorly neuroinvasive prions. PLoS Pathog 9:e1003280.  https://doi.org/10.1371/journal.ppat.1003280 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bett C, Lawrence J, Kurt TD, Orru C, Aguilar-Calvo P, Kincaid AE, Surewicz WK et al (2017) Enhanced neuroinvasion by smaller, soluble prions. Acta neuropathologica communications 5:32.  https://doi.org/10.1186/s40478-017-0430-z CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Bruce ME (2003) TSE strain variation. Br Med Bull 66:99–108PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Calamai M, Kumita JR, Mifsud J, Parrini C, Ramazzotti M, Ramponi G, Taddei N et al (2006) Nature and significance of the interactions between amyloid fibrils and biological polyelectrolytes. Biochemistry 45:12806–12815.  https://doi.org/10.1021/bi0610653 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Capila I, Linhardt RJ (2002) Heparin-protein interactions. Angew Chem Int Ed Engl 41:391–412PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Castillo GM, Ngo C, Cummings J, Wight TN, Snow AD (1997) Perlecan binds to the beta-amyloid proteins (A beta) of Alzheimer’s disease, accelerates A beta fibril formation, and maintains A beta fibril stability. J Neurochem 69:2452–2465CrossRefGoogle Scholar
  17. 17.
    Caughey B, Brown K, Raymond GJ, Katzenstein GE, Thresher W (1994) Binding of the protease-sensitive form of PrP (prion protein) to sulfated glycosaminoglycan and congo red [corrected] [published erratum appears in J Virol 1994 Jun; 68(6):4107]. J Virol 68:2135–2141PubMedPubMedCentralGoogle Scholar
  18. 18.
    Caughey B, Raymond GJ (1991) The scrapie-associated form of PrP is made from a cell surface precursor that is both protease- and phospholipase-sensitive. J Biol Chem 266:18217–18223PubMedPubMedCentralGoogle Scholar
  19. 19.
    Caughey B, Raymond GJ (1993) Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells. J Virol 67:643–650PubMedPubMedCentralGoogle Scholar
  20. 20.
    Caughey BW, Dong A, Bhat KS, Ernst D, Hayes SF, Caughey WS (1991) ) Secondary structure analysis of the scrapie-associated protein PrP 27-30 in water by infrared spectroscopy [published erratum appears in Biochemistry 1991 Oct 29;30(43):10600]. Biochemistry 30:7672–7680PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Chesebro B, Trifilo M, Race R, Meade-White K, Teng C, LaCasse R et al (2005) Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 308:1435–1439PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Cohlberg JA, Li J, Uversky VN, Fink AL (2002) Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from alpha-synuclein in vitro. Biochemistry 41:1502–1511PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Cracco L, Xiao X, Nemani SK, Lavrich J, Cali I, Ghetti B et al (2019) Gerstmann–Straussler–Scheinker disease revisited: accumulation of covalently-linked multimers of internal prion protein fragments. Acta Neuropathol Commun 7:85.  https://doi.org/10.1186/s40478-019-0734-2 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Dlouhy SR, Hsiao K, Farlow MR, Foroud T, Conneally PM, Johnson P et al (1992) Linkage of the Indiana kindred of Gerstmann–Straussler–Scheinker disease to the prion protein gene. Nat Genet 1:64–67PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Doh-ura K, Ishikawa K, Murakami-Kubo I, Sasaki K, Mohri S, Race R et al (2004) Treatment of transmissible spongiform encephalopathy by intraventricular drug infusion in animal models. J Virol 78:4999–5006PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Duchesne L, Octeau V, Bearon RN, Beckett A, Prior IA, Lounis B et al (2012) Transport of fibroblast growth factor 2 in the pericellular matrix is controlled by the spatial distribution of its binding sites in heparan sulfate. PLoS Biol 10:e1001361.  https://doi.org/10.1371/journal.pbio.1001361 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ehlers B, Diringer H (1984) Dextran sulphate 500 delays and prevents mouse scrapie by impairment of agent replication in spleen. J Gen Virol 65:1325–1330PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Farquhar CF, Dickinson AG (1986) Prolongation of scrapie incubation period by an injection of dextran sulphate 500 within the month before or after infection. J Gen Virol 67:463–473PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Fenstermacher JD, Ghersi-Egea JF, Finnegan W, Chen JL (1997) The rapid flow of cerebrospinal fluid from ventricles to cisterns via subarachnoid velae in the normal rat. Acta Neurochir Suppl 70:285–287PubMedPubMedCentralGoogle Scholar
  31. 31.
    Fischer M, Rülicke T, Raeber A, Sailer A, Moser M, Oesch B et al (1996) Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie. EMBO J 15:1255–1264PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Geschwind MD (2016) Prion diseases. In: Daroff RBJJ, Mazziota JC, Pomero SL (eds) Bradley’s neurology in clinical practice 7th edn. Elsevier/Saunders, London, pp 1365–1379Google Scholar
  33. 33.
    Geschwind MD, Josephs KA, Parisi JE, Keegan BM (2007) A 54-year-old man with slowness of movement and confusion. Neurology 69:1881–1887.  https://doi.org/10.1212/01.wnl.0000290370.14036.69 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ghetti B, Dlouhy SR, Giaccone G, Bugiani O, Frangione B, Farlow MR et al (1995) Gerstmann–Straussler–Scheinker disease and the Indiana kindred. Brain Pathol 5:61–75PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Ghetti B, Piccardo P, Frangione B, Bugiani O, Giaccone G, Young K, Prelli F et al (1996) Prion protein amyloidosis. Brain Pathol 6:127–145PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Ghetti B, Piccardo P, Spillantini MG, Ichimiya Y, Porro M, Perini F et al (1996) Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci USA 93:744–748PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Ghetti B, Tagliavini F, Giaccone G, Bugiani O, Frangione B, Farlow MR et al (1994) Familial Gerstmann–Straussler–Scheinker disease with neurofibrillary tangles. Mol Neurobiol 8:41–48.  https://doi.org/10.1007/BF02778006 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Giaccone G, Verga L, Bugiani O, Frangione B, Serban D, Prusiner SB et al (1992) Prion protein preamyloid and amyloid deposits in Gerstmann-Straussler-Scheinker disease, Indiana kindred [published erratum appears in Proc Natl Acad Sci U S A 1993 Jan 1;90(1):302]. Proc Natl Acad Sci USA 89:9349–9353PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Gibson RM, Meyer AM, Winner D, Archer J, Feyertag F, Ruiz-Mateos E et al (2014) Sensitive deep-sequencing-based HIV-1 genotyping assay to simultaneously determine susceptibility to protease, reverse transcriptase, integrase, and maturation inhibitors, as well as HIV-1 coreceptor tropism. Antimicrob Agents Chemother 58:2167–2185.  https://doi.org/10.1128/aac.02710-13 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hijazi N, Kariv-Inbal Z, Gasset M, Gabizon R (2005) PrPSc incorporation to cells requires endogenous glycosaminoglycan expression. J Biol Chem 280:17057–17061PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Holmes BB, DeVos SL, Kfoury N, Li M, Jacks R, Yanamandra K et al (2013) Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. Proc Natl Acad Sci USA 110:E3138–3147.  https://doi.org/10.1073/pnas.1301440110 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Horonchik L, Tzaban S, Ben-Zaken O, Yedidia Y, Rouvinski A, Papy-Garcia D et al (2005) Heparan sulfate is a cellular receptor for purified infectious prions. J Biol Chem 280:17062–17067PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Hsiao K, Baker HF, Crow TJ, Poulter M, Owen F, Terwilliger JD et al (1989) Linkage of a prion protein missense variant to Gerstmann–Sträussler syndrome. Nature 338:342–345PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Hsiao K, Dlouhy SR, Farlow MR, Cass C, Da Costa M, Conneally PM et al (1992) Mutant prion proteins in Gerstmann–Straussler–Scheinker disease with neurofibrillary tangles. Nat Genet 1:68–71PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Ihse E, Yamakado H, van Wijk XM, Lawrence R, Esko JD, Masliah E (2017) Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type. Sci Rep 7:9008.  https://doi.org/10.1038/s41598-017-08720-5 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Imamura M, Tabeta N, Kato N, Matsuura Y, Iwamaru Y, Yokoyama T et al (2016) Heparan sulfate and heparin promote faithful prion replication in vitro by binding to normal and abnormal prion proteins in protein misfolding cyclic amplification. J Biol Chem 291:26478–26486.  https://doi.org/10.1074/jbc.M116.745851 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S (1998) Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res 57:1–9PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Jansen C, Parchi P, Capellari S, Vermeij AJ, Corrado P, Baas F et al (2010) Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP. Acta Neuropathol 119:189–197.  https://doi.org/10.1007/s00401-009-0609-x CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Kascsak RJ, Rubenstein R, Merz PA, Tonna DeMasi M, Fersko R, Carp RI et al (1987) Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. J Virol 61:3688–3693PubMedPubMedCentralGoogle Scholar
  50. 50.
    Kim MO, Cali I, Oehler A, Fong JC, Wong K, See T et al (2013) Genetic CJD with a novel E200G mutation in the prion protein gene and comparison with E200 K mutation cases. Acta Neuropathol Commun 1:80.  https://doi.org/10.1186/2051-5960-1-80 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Kim MO, Takada LT, Wong K, Forner SA, Geschwind MD (2018) Genetic PrP Prion Diseases. Cold Spring Harb Perspect Biol.  https://doi.org/10.1101/cshperspect.a033134 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Klingeborn M, Race B, Meade-White KD, Rosenke R, Striebel JF, Chesebro B (2011) Crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection. J Virol 85:1484–1494.  https://doi.org/10.1128/JVI.02167-10 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Kong Q, Zheng M, Casalone C, Qing L, Huang S, Chakraborty B et al (2008) Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain. J Virol 82:3697–3701.  https://doi.org/10.1128/JVI.02561-07 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Kovalchuk Ben-Zaken O, Nissan I, Tzaban S, Taraboulos A, Zcharia E, Matzger S et al (2015) Transgenic over-expression of mammalian heparanase delays prion disease onset and progression. Biochem Biophys Res Commun 464:698–704.  https://doi.org/10.1016/j.bbrc.2015.06.170 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Kretzschmar HA, Honold G, Seitelberger F, Feucht M, Wessely P, Mehraein P et al (1991) Prion protein mutation in family first reported by Gerstmann, Straussler, and Scheinker [letter]. Lancet 337:1160PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Ladogana A, Casaccia P, Ingrosso L, Cibati M, Salvatore M, Xi YG et al (1992) Sulphate polyanions prolong the incubation period of scrapie-infected hamsters. J Gen Virol 73:661–665PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Larramendy-Gozalo C, Barret A, Daudigeos E, Mathieu E, Antonangeli L, Riffet C et al (2007) Comparison of CR57, a new heparan mimetic, and pentosan polysulfate in the treatment of prion diseases. J Gen Virol 88:1062–1067.  https://doi.org/10.1099/vir.0.82286-0 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Lawrence R, Brown JR, Al-Mafraji K, Lamanna WC, Beitel JR, Boons GJ, Esko JD et al (2012) Disease-specific non-reducing end carbohydrate biomarkers for mucopolysaccharidoses. Nat Chem Biol 8:197–204.  https://doi.org/10.1038/nchembio.766 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Lawrence R, Olson SK, Steele RE, Wang L, Warrior R, Cummings RD, Esko JD (2008) Evolutionary differences in glycosaminoglycan fine structure detected by quantitative glycan reductive isotope labeling. J Biol Chem 283:33674–33684.  https://doi.org/10.1074/jbc.M804288200 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Lin X, Wei G, Shi Z, Dryer L, Esko JD, Wells DE et al (2000) Disruption of gastrulation and heparan sulfate biosynthesis in EXT1-deficient mice. Dev Biol 224:299–311.  https://doi.org/10.1006/dbio.2000.9798 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Lindahl B, Lindahl U (1997) Amyloid-specific heparan sulfate from human liver and spleen. J Biol Chem 272:26091–26094.  https://doi.org/10.1074/jbc.272.42.26091 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Lindahl B, Westling C, Gimenez-Gallego G, Lindahl U, Salmivirta M (1999) Common binding sites for beta-amyloid fibrils and fibroblast growth factor-2 in heparan sulfate from human cerebral cortex. J Biol Chem 274:30631–30635PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Linsenmeier L, Mohammadi B, Wetzel S, Puig B, Jackson WS, Hartmann A et al (2018) Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein. Mol Neurodegener 13:18.  https://doi.org/10.1186/s13024-018-0248-6 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Liu CC, Zhao N, Yamaguchi Y, Cirrito JR, Kanekiyo T, Holtzman DM et al (2016) Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid-beta clearance and aggregation in Alzheimer’s disease. Sci Transl Med 8:332ra344.  https://doi.org/10.1126/scitranslmed.aad3650 CrossRefGoogle Scholar
  65. 65.
    Magnusson K, Simon R, Sjolander D, Sigurdson CJ, Hammarstrom P, Nilsson KP (2014) Multimodal fluorescence microscopy of prion strain specific PrP deposits stained by thiophene-based amyloid ligands. Prion 8:319–329.  https://doi.org/10.4161/pri.29239 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    McBride PA, Wilson MI, Eikelenboom P, Tunstall A, Bruce ME (1998) Heparan sulfate proteoglycan is associated with amyloid plaques and neuroanatomically targeted PrP pathology throughout the incubation period of scrapie-infected mice. Exp Neurol 149:447–454PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Naslavsky N, Stein R, Yanai A, Friedlander G, Taraboulos A (1997) Characterization of detergent-insoluble complexes containing the cellular prion protein and its scrapie isoform. J Biol Chem 272:6324–6331PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Newman PK, Todd NV, Scoones D, Mead S, Knight RS, Will RG et al (2014) Postmortem findings in a case of variant Creutzfeldt–Jakob disease treated with intraventricular pentosan polysulfate. J Neurol Neurosurg Psychiatry 85:921–924.  https://doi.org/10.1136/jnnp-2013-305590 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Noborn F, O’Callaghan P, Hermansson E, Zhang X, Ancsin JB, Damas AM et al (2011) Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein. Proc Natl Acad Sci USA 108:5584–5589.  https://doi.org/10.1073/pnas.1101194108 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Notari S, Strammiello R, Capellari S, Giese A, Cescatti M, Grassi J et al (2008) Characterization of truncated forms of abnormal prion protein in Creutzfeldt–Jakob disease. J Biol Chem 283:30557–30565.  https://doi.org/10.1074/jbc.M801877200 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Nystrom S, Back M, Nilsson KPR, Hammarstrom P (2017) Imaging amyloid tissues stained with luminescent conjugated oligothiophenes by hyperspectral confocal microscopy and fluorescence lifetime imaging. J Vis Exp JoVE:  https://doi.org/10.3791/56279 CrossRefGoogle Scholar
  72. 72.
    Okada M, Nadanaka S, Shoji N, Tamura J, Kitagawa H (2010) Biosynthesis of heparan sulfate in EXT1-deficient cells. Biochem J 428:463–471.  https://doi.org/10.1042/bj20100101 CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Olson ST, Halvorson HR, Bjork I (1991) Quantitative characterization of the thrombin-heparin interaction. Discrimination between specific and nonspecific binding models. J Biol Chem 266:6342–6352PubMedPubMedCentralGoogle Scholar
  74. 74.
    Orru CD, Soldau K, Cordano C, Llibre-Guerra J, Green AJ, Sanchez H et al (2018) Prion seeds distribute throughout the eyes of sporadic Creutzfeldt–Jakob Disease Patients. mBio.  https://doi.org/10.1128/mbio.02095-18 CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Oskarsson ME, Singh K, Wang J, Vlodavsky I, Li JP, Westermark GT (2015) Heparan sulfate proteoglycans are important for islet amyloid formation and islet amyloid polypeptide-induced apoptosis. J Biol Chem 290:15121–15132.  https://doi.org/10.1074/jbc.M114.631697 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Pan KM, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D et al (1993) Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci USA 90:10962–10966.  https://doi.org/10.1073/pnas.90.23.10962 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Pan T, Wong BS, Liu T, Li R, Petersen RB, Sy MS (2002) Cell-surface prion protein interacts with glycosaminoglycans. Biochem J 368:81–90.  https://doi.org/10.1042/bj20020773 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Parchi P, Chen SG, Brown P, Zou W, Capellari S, Budka H et al (1998) Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann–Straussler–Scheinker disease. Proc Natl Acad Sci USA 95:8322–8327PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Parchi P, Zou W, Wang W, Brown P, Capellari S, Ghetti B et al (2000) Genetic influence on the structural variations of the abnormal prion protein. Proc Natl Acad Sci USA 97:10168–10172PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Parry A, Baker I, Stacey R, Wimalaratna S (2007) Long term survival in a patient with variant Creutzfeldt–Jakob disease treated with intraventricular pentosan polysulphate. J Neurol Neurosurg Psychiatry 78:733–734.  https://doi.org/10.1136/jnnp.2006.104505 CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Pellegrini L, Burke DF, von Delft F, Mulloy B, Blundell TL (2000) Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin. Nature 407:1029–1034.  https://doi.org/10.1038/35039551 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Peretz D, Williamson RA, Legname G, Matsunaga Y, Vergara J, Burton DR et al (2002) A change in the conformation of prions accompanies the emergence of a new prion strain. Neuron 34:921–932PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Piccardo P, Liepnieks JJ, William A, Dlouhy SR, Farlow MR, Young K et al (2001) Prion proteins with different conformations accumulate in Gerstmann–Straussler–Scheinker disease caused by A117V and F198S mutations. Am J Pathol 158:2201–2207.  https://doi.org/10.1016/S0002-9440(10)64692-5 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Piccardo P, Seiler C, Dlouhy SR, Young K, Farlow MR, Prelli F et al (1996) Proteinase-K-Resistant prion protein isoforms In Gerstmann–Straussler–Scheinker disease (Indiana Kindred). J Neuropathol Exp Neurol 55:1157–1163PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Polymenidou M, Moos R, Scott M, Sigurdson C, Shi YZ, Yajima B et al (2008) The POM monoclonals: a comprehensive set of antibodies to non-overlapping prion protein epitopes. PLoS One 3:e3872.  https://doi.org/10.1371/journal.pone.0003872 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Prusiner SB (1991) Molecular biology of prion diseases. Science 252:1515–1522PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216:136–144PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Rauch JN, Chen JJ, Sorum AW, Miller GM, Sharf T, See SK et al (2018) Tau internalization is regulated by 6-O sulfation on heparan sulfate proteoglycans (HSPGs). Sci Rep 8:6382.  https://doi.org/10.1038/s41598-018-24904-z CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Raymond GJ, Chabry J (2004) Methods and Tools in Biosciences and Medicine. In: Lehmann S, Grassi J (eds) Techniques in prion research. Birkhäuser, Basel, pp 16–26CrossRefGoogle Scholar
  90. 90.
    Revesz T, Holton JL, Lashley T, Plant G, Frangione B, Rostagno A et al (2009) Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol 118:115–130.  https://doi.org/10.1007/s00401-009-0501-8 CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Roeber S, Krebs B, Neumann M, Windl O, Zerr I, Grasbon-Frodl EM et al (2005) Creutzfeldt–Jakob disease in a patient with an R208H mutation of the prion protein gene (PRNP) and a 17-kDa prion protein fragment. Acta Neuropathol (Berl) 109:443–448CrossRefGoogle Scholar
  92. 92.
    Salanga CL, Handel TM (2011) Chemokine oligomerization and interactions with receptors and glycosaminoglycans: the role of structural dynamics in function. Exp Cell Res 317:590–601.  https://doi.org/10.1016/j.yexcr.2011.01.004 CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Sarrazin S, Lamanna WC, Esko JD (2011) Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol.  https://doi.org/10.1101/cshperspect.a004952 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Shyng SL, Lehmann S, Moulder KL, Harris DA (1995) Sulfated glycans stimulate endocytosis of the cellular isoform of the prion protein, PrPC, in cultured cells. J Biol Chem 270:30221–30229PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Sigurdson CJ, Manco G, Schwarz P, Liberski P, Hoover EA, Hornemann S et al (2006) Strain fidelity of chronic wasting disease upon murine adaptation. J Virol 80:12303–12311PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Snow AD, Kisilevsky R, Willmer J, Prusiner SB, DeArmond SJ (1989) Sulfated glycosaminoglycans in amyloid plaques of prion diseases. Acta Neuropathol Berl 77:337–342PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Snow AD, Mar H, Nochlin D, Kimata K, Kato M, Suzuki S et al (1988) The presence of heparan sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer’s disease. Am J Pathol 133:456–463PubMedPubMedCentralGoogle Scholar
  98. 98.
    Snow AD, Wight TN, Nochlin D, Koike Y, Kimata K, DeArmond SJ et al (1990) Immunolocalization of heparan sulfate proteoglycans to the prion protein amyloid plaques of Gerstmann–Straussler syndrome, Creutzfeldt–Jakob disease and scrapie. Lab Invest 63:601–611PubMedPubMedCentralGoogle Scholar
  99. 99.
    Solomon JP, Bourgault S, Powers ET, Kelly JW (2011) Heparin binds 8 kDa gelsolin cross-beta-sheet oligomers and accelerates amyloidogenesis by hastening fibril extension. Biochemistry 50:2486–2498.  https://doi.org/10.1021/bi101905n CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Spillantini MG, Tolnay M, Love S, Goedert M (1999) Microtubule-associated protein tau, heparan sulphate and alpha-synuclein in several neurodegenerative diseases with dementia. Acta Neuropathol 97:585–594PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Spudich S, Mastrianni JA, Wrensch M, Gabizon R, Meiner Z, Kahana I et al (1995) Complete penetrance of Creutzfeldt–Jakob disease in Libyan Jews carrying the E200 K mutation in the prion protein gene. Mol Med 1:607–613PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Staffaroni AM, Elahi FM, McDermott D, Marton K, Karageorgiou E, Sacco S, Paoletti M et al (2017) Neuroimaging in dementia. Semin Neurol 37:510–537.  https://doi.org/10.1055/s-0037-1608808 CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Stahl N, Baldwin MA, Burlingame AL, Prusiner SB (1990) Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein. Biochemistry 29:8879–8884PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Stahl N, Borchelt DR, Hsiao K, Prusiner SB (1987) Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell 51:229–240PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Stopschinski BE, Holmes BB, Miller GM, Manon VA, Vaquer-Alicea J, Prueitt WL et al (2018) Specific glycosaminoglycan chain length and sulfation patterns are required for cell uptake of tau versus alpha-synuclein and beta-amyloid aggregates. J Biol Chem 293:10826–10840.  https://doi.org/10.1074/jbc.RA117.000378 CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Tagliavini F, Prelli F, Porro M, Salmona M, Bugiani O, Frangione B (1992) A soluble form of prion protein in human cerebrospinal fluid: implications for prion-related encephalopathies. Biochem Biophys Res Commun 184:1398–1404PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Todd NV, Morrow J, Doh-ura K, Dealler S, O’Hare S, Farling P et al (2005) Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt–Jakob disease. J Infect 50:394–396PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    van Horssen J, Kleinnijenhuis J, Maass CN, Rensink AA, Otte-Holler I, David G et al (2002) Accumulation of heparan sulfate proteoglycans in cerebellar senile plaques. Neurobiol Aging 23:537–545PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Vieira TC, Cordeiro Y, Caughey B, Silva JL (2014) Heparin binding confers prion stability and impairs its aggregation. FASEB J 28:2667–2676.  https://doi.org/10.1096/fj.13-246777 CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Wadsworth JDF, Joiner S, Hill AF, Campbell TA, Desbruslais M, Luthert PJ et al (2001) Tissue distribution of protease resistant prion protein in variant CJD using a highly sensitive immuno-blotting assay. Lancet 358:171–180PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Wang F, Wang X, Yuan CG, Ma J (2010) Generating a prion with bacterially expressed recombinant prion protein. Science 327:1132–1135.  https://doi.org/10.1126/science.1183748 CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Webb TE, Poulter M, Beck J, Uphill J, Adamson G, Campbell T, Linehan J, Powell C et al (2008) Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series. Brain 131:2632–2646.  https://doi.org/10.1093/brain/awn202 CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Wong C, Xiong LW, Horiuchi M, Raymond L, Wehrly K, Chesebro B et al (2001) Sulfated glycans and elevated temperature stimulate PrP(Sc)-dependent cell-free formation of protease-resistant prion protein. EMBO J 20:377–386PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Xu D, Esko JD (2014) Demystifying heparan sulfate-protein interactions. Annu Rev Biochem 83:129–157.  https://doi.org/10.1146/annurev-biochem-060713-035314 CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Xu D, Young JH, Krahn JM, Song D, Corbett KD, Chazin WJ et al (2013) Stable RAGE-heparan sulfate complexes are essential for signal transduction. ACS Chem Biol 8:1611–1620.  https://doi.org/10.1021/cb4001553 CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Zanusso G, Fiorini M, Ferrari S, Meade-White K, Barbieri I, Brocchi E et al (2014) Gerstmann–Straussler–Scheinker disease and “anchorless prion protein” mice share prion conformational properties diverging from sporadic Creutzfeldt–Jakob disease. J Biol Chem 289:4870–4881.  https://doi.org/10.1074/jbc.M113.531335 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Patricia Aguilar-Calvo
    • 1
  • Alejandro M. Sevillano
    • 1
  • Jaidev Bapat
    • 1
  • Katrin Soldau
    • 1
  • Daniel R. Sandoval
    • 2
  • Hermann C. Altmeppen
    • 3
  • Luise Linsenmeier
    • 3
  • Donald P. Pizzo
    • 1
  • Michael D. Geschwind
    • 4
  • Henry Sanchez
    • 4
  • Brian S. Appleby
    • 5
    • 6
  • Mark L. Cohen
    • 5
    • 6
  • Jiri G. Safar
    • 5
    • 6
  • Steven D. Edland
    • 7
    • 8
  • Markus Glatzel
    • 3
  • K. Peter R. Nilsson
    • 9
  • Jeffrey D. Esko
    • 2
  • Christina J. Sigurdson
    • 1
    • 10
    • 11
    Email author
  1. 1.Department of PathologyUniversity of California, San Diego (UCSD)La JollaUSA
  2. 2.Department of Cellular and Molecular MedicineUniversity of California, San Diego (UCSD)La JollaUSA
  3. 3.Institute of NeuropathologyUniversity Medical Center Hamburg-Eppendorf (UKE)HamburgGermany
  4. 4.Department of Neurology, Memory and Aging CenterUniversity of California, San Francisco (UCSF)San FranciscoUSA
  5. 5.Departments of Pathology and NeurologyCase Western Reserve UniversityClevelandUSA
  6. 6.National Prion Disease Pathology Surveillance CenterCase Western Reserve UniversityClevelandUSA
  7. 7.Department of Family Medicine and Public HealthUniversity of California, San Diego (UCSD)La JollaUSA
  8. 8.Department of NeurosciencesUniversity of California, San Diego (UCSD)La JollaUSA
  9. 9.Department of Physics, Chemistry, and BiologyLinköping UniversityLinköpingSweden
  10. 10.Department of MedicineUniversity of California, San Diego (UCSD)La JollaUSA
  11. 11.Department of Pathology, Immunology, and MicrobiologyUniversity of California, Davis (UCD)DavisUSA

Personalised recommendations