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Inhibition of Transthyretin Fibrillogenesis Using a Conformation Specific Antibody

Immunoglobulin-mediated inhibition of amyloid fibril formation in vivo is a promising strategy for the treatment of protein misfolding diseases such as the amyloidoses. Here we focus on transthyretin amyloidoses, a group of protein conformation diseases caused by the misfolding of the serum protein transthyretin into fibrillar structures that deposit in specific organs and tissues—often with serious pathological consequences. Using a structure-guided immunological approach, we report a novel antibody that selectively recognizes monomeric, misfolded conformations of transthyretin in vitro. Raised to an epitope normally buried in the native form of transthyretin, this antibody was found to suppress transthyretin fibrillogenesis at substoichiometric concentrations in vitro. Overall, the selectivity and inhibitory nature of the antibody signals the potential use of conformation specific antibodies in the diagnosis and treatment of transthyretin amyloidoses, conditions which remain difficult to treat and are widely under/misdiagnosed at the current time.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/32230
Date21 March 2012
CreatorsBugyei-Twum, Antoinette
ContributorsChakrabartty, Avijit
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
Languageen_ca
Detected LanguageEnglish
TypeThesis

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