In vitro inhibition of transthyretin aggregate-induced cytotoxicity by full and peptide derived forms of the soluble receptor for advanced glycation end products (RAGE).
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.
Monteiro
Filipe Almeida
FA
Molecular Neurobiology, Instituto de Biologia Celular e Molecular, Porto, Portugal.
Cardoso
Isabel
I
Sousa
Mónica Mendes
MM
Saraiva
Maria João
MJ
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
D011228:Prealbumin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011994:Recombinant Proteins