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Implications of Heparan Sulfate and Heparanase in Amyloid Diseases

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Heparanase

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1221))

Abstract

Amyloidosis refers to a group of diseases characterized by abnormal deposition of denatured endogenous proteins, termed amyloid, in the affected organs. Analysis of biopsy and autopsy tissues from patients revealed the presence of heparan sulfate proteoglycans (HSPGs) along with amyloid proteins in the deposits. For a long time, HSPGs were believed to occur in the deposits as an innocent bystander. Yet, the consistent presence of HSPGs in various deposits, regardless of the amyloid species, led to the hypothesis that these macromolecular glycoconjugates might play functional roles in the pathological process of amyloidosis. In vitro studies have revealed that HSPGs, or more precisely, the heparan sulfate (HS) side chains interact with amyloid peptides, thus promoting amyloid fibrillization. Although information on the mechanisms of HS participation in amyloid deposition is limited, recent studies involving a transgenic mouse model of Alzheimer’s disease point to an active role of HS in amyloid formation. Heparanase cleavage alters the molecular structure of HS, and thus modulates the functional roles of HS in homeostasis, as well as in diseases, including amyloidosis. The heparanase transgenic mice have provided models for unveiling the effects of heparanase, through cleavage of HS, in various amyloidosis conditions.

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References

  1. Benson, M. D., Buxbaum, J. N., Eisenberg, D. S., Merlini, G., Saraiva, M. J. M., Sekijima, Y., et al. (2018). Amyloid nomenclature 2018: Recommendations by the international society of Amyloidosis (ISA) nomenclature committee. Amyloid, 25(4), 215–219.

    Article  CAS  PubMed  Google Scholar 

  2. Sipe, J. D., Benson, M. D., Buxbaum, J. N., Ikeda, S. I., Merlini, G., Saraiva, M. J., et al. (2016). Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification international society of Amyloidosis 2016 nomenclature guidelines. Amyloid, 23(4), 209–213.

    Article  CAS  PubMed  Google Scholar 

  3. van Horssen, J., Wesseling, P., van den Heuvel, L. P., de Waal, R. M., & Verbeek, M. M. (2003). Heparan sulphate proteoglycans in Alzheimer’s disease and amyloid-related disorders. Lancet Neurology, 2(8), 482–492.

    Article  PubMed  Google Scholar 

  4. Ancsin, J. B. (2003). Amyloidogenesis: Historical and modern observations point to heparan sulfate proteoglycans as a major culprit. Amyloid, 10(2), 67–79.

    Article  CAS  PubMed  Google Scholar 

  5. Sipe, J. D., & Cohen, A. S. (2000). Review: History of the amyloid fibril. Journal of Structural Biology, 130(2–3), 88–98.

    Article  CAS  PubMed  Google Scholar 

  6. Chiti, F., & Dobson, C. M. (2006). Protein misfolding, functional amyloid, and human disease. Annual Review of Biochemistry, 75, 333–366.

    Article  CAS  PubMed  Google Scholar 

  7. Hardy, J., & Selkoe, D. J. (2002). The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science, 297(5580), 353–356.

    Article  CAS  PubMed  Google Scholar 

  8. Querfurth, H. W., & LaFerla, F. M. (2010). Alzheimer’s disease. The New England Journal of Medicine, 362(4), 329–344.

    Article  CAS  PubMed  Google Scholar 

  9. Westermark, P., Wilander, E., & Johnson, K. H. (1987). Islet amyloid polypeptide. Lancet, 2(8559), 623.

    Article  CAS  PubMed  Google Scholar 

  10. Sanke, T., Bell, G. I., Sample, C., Rubenstein, A. H., & Steiner, D. F. (1988). An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing. The Journal of Biological Chemistry, 263(33), 17243–17246.

    CAS  PubMed  Google Scholar 

  11. Westermark, P., Wernstedt, C., Wilander, E., Hayden, D. W., O’Brien, T. D., & Johnson, K. H. (1987). Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. Proceedings of the National Academy of Sciences of the United States of America, 84(11), 3881–3885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Westermark, P., Engstrom, U., Westermark, G. T., Johnson, K. H., Permerth, J., & Betsholtz, C. (1989). Islet amyloid polypeptide (IAPP) and pro-IAPP immunoreactivity in human islets of Langerhans. Diabetes Research and Clinical Practice, 7(3), 219–226.

    Article  CAS  PubMed  Google Scholar 

  13. Hull, R. L., Westermark, G. T., Westermark, P., & Kahn, S. E. (2004). Islet amyloid: A critical entity in the pathogenesis of type 2 diabetes. The Journal of Clinical Endocrinology and Metabolism, 89(8), 3629–3643.

    Article  CAS  PubMed  Google Scholar 

  14. Merlini, G., & Westermark, P. (2004). The systemic amyloidoses: Clearer understanding of the molecular mechanisms offers hope for more effective therapies. Journal of Internal Medicine, 255(2), 159–178.

    Article  CAS  PubMed  Google Scholar 

  15. Westermark, G. T., Fandrich, M., & Westermark, P. (2015). AA amyloidosis: Pathogenesis and targeted therapy. Annual Review of Pathology, 10, 321–344.

    Article  CAS  PubMed  Google Scholar 

  16. Ledue TB, Weiner DL, Sipe JD, Poulin SE, Collins MF, Rifai N. 1998 Analytical evaluation of particle-enhanced immunonephelometric assays for C-reactive protein, serum amyloid a and mannose-binding protein in human serum. Annals of Clinical Biochemistry;35 ( Pt 6):745–753.

    Google Scholar 

  17. Hawkins, P. N., Ando, Y., Dispenzeri, A., Gonzalez-Duarte, A., Adams, D., & Suhr, O. B. (2015). Evolving landscape in the management of transthyretin amyloidosis. Annals of Medicine, 47(8), 625–638.

    Article  CAS  PubMed  Google Scholar 

  18. Serpell, L. C., Sunde, M., Fraser, P. E., Luther, P. K., Morris, E. P., Sangren, O., et al. (1995). Examination of the structure of the transthyretin amyloid fibril by image reconstruction from electron micrographs. Journal of Molecular Biology, 254(2), 113–118.

    Article  CAS  PubMed  Google Scholar 

  19. Eriksson, M., Buttner, J., Todorov, T., Yumlu, S., Schonland, S., Hegenbart, U., et al. (2009). Prevalence of germline mutations in the TTR gene in a consecutive series of surgical pathology specimens with ATTR amyloid. The American Journal of Surgical Pathology, 33(1), 58–65.

    Article  PubMed  Google Scholar 

  20. Plante-Bordeneuve, V. (2018). Transthyretin familial amyloid polyneuropathy: An update. Journal of Neurology, 265(4), 976–983.

    Article  CAS  PubMed  Google Scholar 

  21. Hou, X., Aguilar, M. I., & Small, D. H. (2007). Transthyretin and familial amyloidotic polyneuropathy. Recent progress in understanding the molecular mechanism of neurodegeneration. The FEBS Journal, 274(7), 1637–1650.

    Article  CAS  PubMed  Google Scholar 

  22. Westermark, P., Bergstrom, J., Solomon, A., Murphy, C., & Sletten, K. (2003). Transthyretin-derived senile systemic amyloidosis: Clinicopathologic and structural considerations. Amyloid, 10(Suppl 1), 48–54.

    Article  CAS  PubMed  Google Scholar 

  23. Mankad, A. K., & Shah, K. B. (2017). Transthyretin cardiac amyloidosis. Current Cardiology Reports, 19(10), 97.

    Article  PubMed  Google Scholar 

  24. Snow, A. D., 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. The American Journal of Pathology, 133(3), 456–463.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 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. The Journal of Biological Chemistry, 274(43), 30631–30635.

    Article  CAS  PubMed  Google Scholar 

  26. Noborn, F., O’Callaghan, P., Hermansson, E., Zhang, X., Ancsin, J. B., Damas, A. M., et al. (2011). Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein. PNAS, 108(14), 5584–5589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Oskarsson, M. E., Singh, K., Wang, J., Vlodavsky, I., Li, J. P., & Westermark, G. T. (2015). Heparan sulfate proteoglycans are important for islet amyloid formation and islet amyloid polypeptide-induced apoptosis. The Journal of Biological Chemistry, 290(24), 15121–15132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Digre, A., Nan, J., Frank, M., & Li, J. P. (2016). Heparin interactions with apoA1 and SAA in inflammation-associated HDL. Biochemical and Biophysical Research Communications, 474(2), 309–314.

    Article  CAS  PubMed  Google Scholar 

  29. Li JP, Galvis ML, Gong F, Zhang X, Zcharia E, Metzger S, et al. In vivo fragmentation of heparan sulfate by heparanase overexpression renders mice resistant to amyloid protein a amyloidosis. Proceedings of the National Academy of Sciences of the United States of America 2005;102(18):6473–6477.

    Google Scholar 

  30. Wang, B., Tan, Y. X., Jia, J., Digre, A., Zhang, X., Vlodavsky, I., et al. (2012). Accelerated resolution of AA amyloid in Heparanase knockout mice is associated with matrix Metalloproteases. PLoS One, 7(7), e39899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Jendresen, C. B., Cui, H., Zhang, X., Vlodavsky, I., Nilsson, L. N., & Li, J. P. (2015). Overexpression of Heparanase lowers the amyloid burden in amyloid-beta precursor protein transgenic mice. The Journal of Biological Chemistry, 290(8), 5053–5064.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang, X., Wang, B., O’Callaghan, P., Hjertstrom, E., Jia, J., Gong, F., et al. (2012). Heparanase overexpression impairs inflammatory response and macrophage-mediated clearance of amyloid-beta in murine brain. Acta Neuropathologica, 124(4), 465–478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Garcia, B., Martin, C., Garcia-Suarez, O., Muniz-Alonso, B., Ordiales, H., Fernandez-Menendez, S., et al. (2017). Upregulated expression of Heparanase and Heparanase 2 in the brains of Alzheimer’s disease. Journal of Alzheimer’s Disease, 58(1), 185–192.

    Article  CAS  PubMed  Google Scholar 

  34. Snow, A. D., & Willmer, J. (1987). Kisilevsky R. a close ultrastructural relationship between sulfated proteoglycans and AA amyloid fibrils. Laboratory Investigation, 57(6), 687–698.

    CAS  PubMed  Google Scholar 

  35. Donahue, J. E., Berzin, T. M., Rafii, M. S., Glass, D. J., Yancopoulos, G. D., Fallon, J. R., et al. (1999). Agrin in Alzheimer’s disease: Altered solubility and abnormal distribution within microvasculature and brain parenchyma. Proceedings of the National Academy of Sciences of the United States of America, 96(11), 6468–6472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. O’Callaghan, P., Sandwall, E., Li, J. P., Yu, H., Ravid, R., Guan, Z. Z., et al. (2008). Heparan sulfate accumulation with Abeta deposits in Alzheimer’s disease and Tg2576 mice is contributed by glial cells. Brain Pathology, 18(4), 548–561.

    PubMed  PubMed Central  Google Scholar 

  37. Bruinsma, I. B., te Riet, L., Gevers, T., ten Dam, G. B., van Kuppevelt, T. H., David, G., et al. (2010). Sulfation of heparan sulfate associated with amyloid-beta plaques in patients with Alzheimer’s disease. Acta Neuropathologica, 119(2), 211–220.

    Article  CAS  PubMed  Google Scholar 

  38. Magnus, J. H., Stenstad, T., Kolset, S. O., & Husby, G. (1991). Glycosaminoglycans in extracts of cardiac amyloid fibrils from familial amyloid cardiomyopathy of Danish origin related to variant transthyretin met 111. Scandinavian Journal of Immunology, 34(1), 63–69.

    Article  CAS  PubMed  Google Scholar 

  39. Dahm, C. N., Cornell, R. F., & Lenihan, D. J. (2018). Advances in treatment of cardiac amyloid. Current Treatment Options in Cardiovascular Medicine, 20(5), 37.

    Article  PubMed  Google Scholar 

  40. Young, I. D., Ailles, L., Narindrasorasak, S., Tan, R., & Kisilevsky, R. (1992). Localization of the basement membrane heparan sulfate proteoglycan in islet amyloid deposits in type II diabetes mellitus. Archives of Pathology & Laboratory Medicine, 116(9), 951–954.

    CAS  Google Scholar 

  41. Kahn, S. E., Andrikopoulos, S., & Verchere, C. B. (1999). Islet amyloid: A long-recognized but underappreciated pathological feature of type 2 diabetes. Diabetes, 48(2), 241–253.

    Article  CAS  PubMed  Google Scholar 

  42. Gruys, E., & Snel, F. W. (1994). Animal models for reactive amyloidosis. Baillière’s Clinical Rheumatology, 8(3), 599–611.

    Article  CAS  PubMed  Google Scholar 

  43. Kisilevsky, R., & Fraser, P. E. (1997). A beta amyloidogenesis: Unique, or variation on a systemic theme? Critical Reviews in Biochemistry and Molecular Biology, 32(5), 361–404.

    Article  CAS  PubMed  Google Scholar 

  44. Narindrasorasak S, Lowery D, Gonzalez-De Whitt.P, Poorman RA, Greenberg B, Kisilevsky R. 1991 High affinity interactions between the Alzheimer’s beta-amyloid precursor proteins and the basement membrane form of heparan sulfate proteoglycan. The Journal of Biological Chemistry;266(20):12878–12883.

    Google Scholar 

  45. Brunden, K. R., Richter-Cook, N. J., Chaturvedi, N., & Frederickson, R. C. (1993). pH-dependent binding of synthetic beta-amyloid peptides to glycosaminoglycans. Journal of Neurochemistry, 61(6), 2147–2154.

    Article  CAS  PubMed  Google Scholar 

  46. Watson, D. J., Lander, A. D., & Selkoe, D. J. (1997). Heparin-binding properties of the amyloidogenic peptides Abeta and amylin. Dependence on aggregation state and inhibition by Congo red. The Journal of Biological Chemistry, 272(50), 31617–31624.

    Article  CAS  PubMed  Google Scholar 

  47. Castillo, G. M., Cummings, J. A., Yang, W., Judge, M. E., Sheardown, M. J., Rimvall, K., et al. (1998). Sulfate content and specific glycosaminoglycan backbone of perlecan are critical for perlecan’s enhancement of islet amyloid polypeptide (amylin) fibril formation. Diabetes, 47(4), 612–620.

    Article  CAS  PubMed  Google Scholar 

  48. Park, K., & Verchere, C. B. (2001). Identification of a heparin binding domain in the N-terminal cleavage site of pro-islet amyloid polypeptide. Implications for islet amyloid formation. The Journal of Biological Chemistry, 276(20), 16611–16616.

    Article  CAS  PubMed  Google Scholar 

  49. Abedini, A., Tracz, S. M., Cho, J. H., & Raleigh, D. P. (2006). Characterization of the heparin binding site in the N-terminus of human pro-islet amyloid polypeptide: Implications for amyloid formation. Biochemistry, 45(30), 9228–9237.

    Article  CAS  PubMed  Google Scholar 

  50. Paulsson, J. F., & Westermark, G. T. (2005). Aberrant processing of human proislet amyloid polypeptide results in increased amyloid formation. Diabetes, 54(7), 2117–2125.

    Article  CAS  PubMed  Google Scholar 

  51. Potter-Perigo, S., Hull, R. L., Tsoi, C., Braun, K. R., Andrikopoulos, S., Teague, J., et al. (2003). Proteoglycans synthesized and secreted by pancreatic islet beta-cells bind amylin. Archives of Biochemistry and Biophysics, 413(2), 182–190.

    Article  CAS  PubMed  Google Scholar 

  52. Hull, R. L., Zraika, S., Udayasankar, J., Kisilevsky, R., Szarek, W. A., Wight, T. N., et al. (2007). Inhibition of glycosaminoglycan synthesis and protein glycosylation with WAS-406 and azaserine result in reduced islet amyloid formation in vitro. American Journal of Physiology. Cell Physiology, 293(5), C1586–C1593.

    Article  CAS  PubMed  Google Scholar 

  53. Ancsin, J. B., & Kisilevsky, R. (1999). The heparin/heparan sulfate-binding site on apo-serum amyloid a. implications for the therapeutic intervention of amyloidosis. The Journal of Biological Chemistry, 274(11), 7172–7181.

    Article  CAS  PubMed  Google Scholar 

  54. Noborn, F., Ancsin, J. B., Ubhayasekera, W., Kisilevsky, R., & Li, J. P. (2012). Heparan sulfate dissociates serum amyloid a (SAA) from acute-phase high-density lipoprotein, promoting SAA aggregation. The Journal of Biological Chemistry, 287(30), 25669–25677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Elimova, E., Kisilevsky, R., Szarek, W. A., & Ancsin, J. B. (2004). Amyloidogenesis recapitulated in cell culture: A peptide inhibitor provides direct evidence for the role of heparan sulfate and suggests a new treatment strategy. The FASEB Journal, 18(14), 1749–1751.

    Article  CAS  PubMed  Google Scholar 

  56. Kisilevsky, R., Szarek, W. A., Ancsin, J. B., Elimova, E., Marone, S., Bhat, S., et al. (2004). Inhibition of amyloid a amyloidogenesis in vivo and in tissue culture by 4-deoxy analogues of peracetylated 2-acetamido-2-deoxy-alpha- and beta-d-glucose: Implications for the treatment of various amyloidoses. The American Journal of Pathology, 164(6), 2127–2137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Lindahl, B., & Lindahl, U. (1997). Amyloid-specific Heparan sulfate from human liver and spleen. The Journal of Biological Chemistry, 272(42), 26091–26094.

    Article  CAS  PubMed  Google Scholar 

  58. Bourgault, S., Solomon, J. P., Reixach, N., & Kelly, J. W. (2011). Sulfated glycosaminoglycans accelerate transthyretin amyloidogenesis by quaternary structural conversion. Biochemistry, 50(6), 1001–1015.

    Article  CAS  PubMed  Google Scholar 

  59. Geneste, A., Andre, C., Magy-Bertrand, N., Lethier, L., Tijani, G., & Guillaume, Y. C. (2015). Thermodynamic study of transthyretin association (wild-type and senile forms) with heparan sulfate proteoglycan: pH effect and implication of the reactive histidine residue. Biomedical Chromatography, 29(4), 514–522.

    Article  CAS  PubMed  Google Scholar 

  60. Snow, A. D., Sekiguchi, R., Nochlin, D., Fraser, P., Kimata, K., Mizutani, A., et al. (1994). An important role of heparan sulfate proteoglycan (Perlecan) in a model system for the deposition and persistence of fibrillar a beta-amyloid in rat brain. Neuron, 12(1), 219–234.

    Article  CAS  PubMed  Google Scholar 

  61. Hart, M., Li, L., Tokunaga, T., Lindsey, J. R., Hassell, J. R., Snow, A. D., et al. (2001). Overproduction of perlecan core protein in cultured cells and transgenic mice. The Journal of Pathology, 194(2), 262–269.

    Article  CAS  PubMed  Google Scholar 

  62. Bergamaschini, L., Rossi, E., Storini, C., Pizzimenti, S., Distaso, M., Perego, C., et al. (2004). Peripheral treatment with enoxaparin, a low molecular weight heparin, reduces plaques and beta-amyloid accumulation in a mouse model of Alzheimer’s disease. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience., 24(17), 4181–4186.

    Article  CAS  Google Scholar 

  63. Zhu, H., Yu, J., & Kindy, M. S. (2001). Inhibition of amyloidosis using low-molecular-weight heparins. Molecular Medicine, 7(8), 517–522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Haass, C., & Selkoe, D. J. (2007). Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer’s amyloid beta-peptide. Nature Reviews. Molecular Cell Biology, 8(2), 101–112.

    Article  CAS  PubMed  Google Scholar 

  65. Sandwall, E., O’Callaghan, P., Zhang, X., Lindahl, U., Lannfelt, L., & Li, J. P. (2010). Heparan sulfate mediates amyloid-beta internalization and cytotoxicity. Glycobiology, 20(5), 533–541.

    Article  CAS  PubMed  Google Scholar 

  66. Sousa, M. M., & Saraiva, M. J. (2001). Internalization of transthyretin. Evidence of a novel yet unidentified receptor-associated protein (RAP)-sensitive receptor. The Journal of Biological Chemistry, 276(17), 14420–14425.

    Article  CAS  PubMed  Google Scholar 

  67. O’Callaghan, P., Li, J. P., Lannfelt, L., Lindahl, U., & Zhang, X. (2015). Microglial Heparan sulfate proteoglycans facilitate the cluster-of-differentiation 14 (CD14)/toll-like receptor 4 (TLR4)-dependent inflammatory response. The Journal of Biological Chemistry, 290(24), 14904–14914.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Zhang, G. L., Zhang, X., Wang, X. M., & Li, J. P. (2014). Towards understanding the roles of heparan sulfate proteoglycans in Alzheimer’s disease. BioMed Research International, 2014, 516028.

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Biochemistry and Microbiology and the SciLifeLab, Uppsala University, Uppsala, Sweden

    Jin-Ping Li

  2. Department of Neuroscience, Uppsala University, Uppsala, Sweden

    Xiao Zhang

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  1. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Israel Vlodavsky

  2. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    Ralph D. Sanderson

  3. Technion Integrated Cancer Center (TICC) Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Haifa, Israel

    Neta Ilan

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Li, JP., Zhang, X. (2020). Implications of Heparan Sulfate and Heparanase in Amyloid Diseases. In: Vlodavsky, I., Sanderson, R., Ilan, N. (eds) Heparanase. Advances in Experimental Medicine and Biology, vol 1221. Springer, Cham. https://doi.org/10.1007/978-3-030-34521-1_25

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