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Arresting amyloidosis in vivo using small-molecule anionic sulphonates or sulphates: implications for Alzheimer's disease

Nature Medicine volume 1, pages 143–148 (1995)Cite this article

Abstract

Amyloid is a term for extracellular protein fibril deposits that have characteristic tinctorial and structural properties. Heparan sulphate, or the heparan sulphate proteoglycan perlecan, has been identified in all amyloids and implicated in the earliest stages of inflammation-associated (AA) amyloid induction. Heparan sulphate interacts with the AA amyloid precursor and the β-peptide of Alzheimer's amyloid, imparting characteristic secondary and tertiary amyloid structural features. These observations suggest that molecules that interfere with this interaction may prevent or arrest amyloidogenesis. We synthesized low-molecular-weight (135–1,000) anionic sulphonate or sulphate compounds. When administered orally, these compounds substantially reduced murine splenic AA amyloid progression. They also interfered with heparan sulphate-stimulated β-peptide fibril aggregation in vitro.

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Authors and Affiliations

  1. Department of Pathology and Biochemistry, Queen's University, and The Syl and Molly Apps Research Center, Kingston General Hospital, Kingston, Ontario, Canada, K7L 3N6

    Robert Kisilevsky

  2. Department of Pathology, Queen's University, Kingston, Ontario, Canada, K7L 3N6

    Laura J. Lemieux

  3. Center for Research in Neurodegenerative Disorders, University of Toronto, Toronto, Ontario, Canada, M5S 1A8

    Paul E. Fraser

  4. Department of Chemistry, Queen's University, Kingston, Ontario, Canada, K7L 3N6

    Xianqi Kong, Philip G. Hultin & Walter A. Szarek

  5. Department of Pathology, Queen's University, Kingston, Ontario, Canada, K7L 3N6

    Robert Kisilevsky

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Kisilevsky, R., Lemieux, L., Fraser, P. et al. Arresting amyloidosis in vivo using small-molecule anionic sulphonates or sulphates: implications for Alzheimer's disease. Nat Med 1, 143–148 (1995). https://doi.org/10.1038/nm0295-143

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