title: Amyloidosis: new strategies for treatment.
abstract: Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Over 20 unrelated proteins form amyloid fibrils in vivo, with fibrils sharing a lamellar cross-beta sheet structure, composed of non-covalently associated protein or peptide subunits. Amyloidosis may be acquired or hereditary and local or systemic, and is defined according to the precursor protein. Of note, local amyloid deposition occurs in Alzheimer's disease (AD) and maturity onset diabetes but their precise role in the pathogenesis of these diseases remains uncertain. Glycosaminoglycans (GAG) and the pentraxin protein, serum amyloid P (SAP) component, are universal non-fibrillar constituents of amyloid deposits that contribute to fibrillogenesis. We review potential therapies for amyloidosis, which include measures to reduce the production of amyloidogenic precursor proteins, interference with fibrillogenesis, and enhancement of amyloid clearance, either by active or passive immunisation or by destabilising deposits through removal of serum amyloid P component.
authors.affiliation: Centre for Amyloidosis, Royal Free University College Medical School, NW3 2PF London, UK. g.hirschfield@rfc.ucl.ac.uk
authors.forename: G M
authors.initials: GM
authors.lastname: Hirschfield
authors.forename: P N
authors.initials: PN
authors.lastname: Hawkins
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000682:Amyloid / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000686:Amyloidosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000628:therapy; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D017510:Protein Folding; D000683:Serum Amyloid P-Component / Q000378:metabolism
chemical_list: D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D006025:Glycosaminoglycans; D000683:Serum Amyloid P-Component