title: Glycosaminoglycan mimetics: a therapeutic approach to cerebral amyloid angiopathy.
abstract: Amyloid deposits characteristic of cerebral amyloid angiopathy lead to vessel rupture and intracerebral hemorrhage. Proteoglycans associate with the amyloid fibril deposits and are thought to play a role in the polymerization of amyloid proteins and the propagation of the deposition process. A series of low molecular weight anionic compounds was developed to mimic the glycosaminoglycan moieties of these proteoglycans. These compounds were tested in different in vitro systems to determine their anti-Abeta amyloid activity. Specific compounds were identified as being anti-fibrillogenic and protective against Abeta-induced cvtotoxicity. Such compounds also did not show intrinsic cellular toxicity could cross the blood-brain barrier (BBB) in vivo, and showed a good safety profile following chronic' exposure. Molecules showing an anti-amyloid profile combined with the ability to cross the BBB represent promising therapeutics for CAA.
authors.affiliation: Neurochem Inc, St-Laurent, Quebec, Canada. fgervais@neurochem.com
authors.forename: F
authors.initials: F
authors.lastname: Gervais
authors.forename: R
authors.initials: R
authors.lastname: Chalifour
authors.forename: D
authors.initials: D
authors.lastname: Garceau
authors.forename: X
authors.initials: X
authors.lastname: Kong
authors.forename: J
authors.initials: J
authors.lastname: Laurin
authors.forename: R
authors.initials: R
authors.lastname: Mclaughlin
authors.forename: C
authors.initials: C
authors.lastname: Morissette
authors.forename: J
authors.initials: J
authors.lastname: Paquette
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D002478:Cells, Cultured; D016657:Cerebral Amyloid Angiopathy / Q000188:drug therapy* / Q000378:metabolism; D002942:Circular Dichroism; D006025:Glycosaminoglycans / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008854:Microscopy, Electron; D018716:Molecular Mimicry; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D006025:Glycosaminoglycans