15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis.

      Nature
      Amyloidosis, blood, drug therapy, metabolism, Animals, Calcium, Carboxylic Acids, chemistry, pharmacology, therapeutic use, Cross-Linking Reagents, Crystallography, X-Ray, Dimerization, Humans, Inhibitory Concentration 50, Liver, Mice, Models, Molecular, Protein Binding, Protein Structure, Quaternary, drug effects, Pyrrolidines, Serum Amyloid P-Component, antagonists & inhibitors

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The normal plasma protein serum amyloid P component (SAP) binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. In order to intervene in this process we have developed a drug, R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid, that is a competitive inhibitor of SAP binding to amyloid fibrils. This palindromic compound also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP. This mechanism of drug action potently removes SAP from human amyloid deposits in the tissues and may provide a new therapeutic approach to both systemic amyloidosis and diseases associated with local amyloid, including Alzheimer's disease and type 2 diabetes.

          Related collections

          Author and article information

          Comments

          Comment on this article