title: In vitro inhibition of transthyretin aggregate-induced cytotoxicity by full and peptide derived forms of the soluble receptor for advanced glycation end products (RAGE).
abstract: Familial amyloidotic polyneuropathy is a neurodegenerative disorder characterized by systemic extracellular deposition of transthyretin (TTR) amyloid fibrils. The latter have been proposed to trigger neurodegeneration through engagement of the receptor for advanced glycation end products (RAGE). Here we show that TTR interaction with RAGE is conserved across mouse and human species and is not dependent on RAGE glycosylation. Moreover, strand D of TTR structure seems important for the TTR-RAGE interaction as well as a motif in RAGE (residues 102-118) located within the V-domain; this motif suppressed TTR aggregate-induced cytotoxicity in cell culture.
authors.affiliation: Molecular Neurobiology, Instituto de Biologia Celular e Molecular, Porto, Portugal.
authors.forename: Filipe Almeida
authors.initials: FA
authors.lastname: Monteiro
authors.forename: Isabel
authors.initials: I
authors.lastname: Cardoso
authors.forename: Mónica Mendes
authors.initials: MM
authors.lastname: Sousa
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Saraiva
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D011228:Prealbumin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D011228:Prealbumin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011994:Recombinant Proteins