Single-domain antibodies recognize selectively small oligomeric forms of amyloid beta, prevent Abeta-induced neurotoxicity and inhibit fibril formation. - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Molecular Immunology Année : 2009

Single-domain antibodies recognize selectively small oligomeric forms of amyloid beta, prevent Abeta-induced neurotoxicity and inhibit fibril formation.

Résumé

Neurotoxic oligomers of amyloid beta (Abeta) peptide have been incriminated in the pathogenesis of Alzheimer's disease. Further exploration of this issue has been hampered to this date by the fact that all previously described anti-Abeta antibodies are unable to discriminate between the different conformations of the peptide (oligomers, protofibrils and fibrils). Here, we describe the generation of novel camelid single-chain binding domains (VHHs) that recognizes specifically low molecular-weight (MW) oligomers. Three VHH specific for Abeta were obtained from an immunized alpaca phage display library. Two were able to recognize selectively intraneuronal Abeta oligomers; furthermore, one of them, V31-1, prevented Abeta-induced neurotoxicity and inhibited fibril formation. This study confirms that VHHs may recognize non-conventional epitopes and illustrates their potential for the immunodiagnostic of diseases due to protein accumulation.

Domaines

Immunothérapie
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Dates et versions

pasteur-00429629 , version 1 (03-11-2009)

Identifiants

Citer

Pierre Lafaye, Ikbel Achour, Patrick England, Charles Duyckaerts, François Rougeon. Single-domain antibodies recognize selectively small oligomeric forms of amyloid beta, prevent Abeta-induced neurotoxicity and inhibit fibril formation.. Molecular Immunology, 2009, 46 (4), pp.695-704. ⟨10.1016/j.molimm.2008.09.008⟩. ⟨pasteur-00429629⟩

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