ARRESTING AMYLOIDOSIS IN-VIVO USING SMALL-MOLECULE ANIONIC SULFONATESOR SULFATES - IMPLICATIONS FOR ALZHEIMERS-DISEASE

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-as sociated (AA) amyloid induction. Heparan sulphate interacts with the A A amyloid precursor and the beta-peptide of Alzheimer's amyloid, impar ting characteristic secondary and tertiary amyloid structural features . These observations suggest that molecules that interfere with this i nteraction may prevent or arrest amyloidogenesis. We synthesized low-m olecular-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 sul phate-stimulated beta-peptide fibril aggregation in vitro.