FEBS Letters
Volume 582, Issue 6 , Pages 936-942, 19 March 2008

Transthyretin binding to A-Beta peptide – Impact on A-Beta fibrillogenesis and toxicity

Edited by Jesus Avila

  • R. Costa

      Affiliations

    • Molecular Neurobiology Unit, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre, 823, 4150-180 Porto, Portugal
    • ,
  • A. Gonçalves

      Affiliations

    • Molecular Neurobiology Unit, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre, 823, 4150-180 Porto, Portugal
    • ,
  • M.J. Saraiva

      Affiliations

    • Molecular Neurobiology Unit, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre, 823, 4150-180 Porto, Portugal
    • ICBAS, University of Porto, Porto, Portugal
    • ,
  • I. Cardoso

      Affiliations

    • Molecular Neurobiology Unit, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre, 823, 4150-180 Porto, Portugal
    • Corresponding Author InformationCorresponding author. Fax: +351 22 6074905.

Received 15 January 2008; received in revised form 31 January 2008; accepted 11 February 2008. published online 22 February 2008.

Abstract 

It has been suggested that transthyretin (TTR) is involved in preventing A-Beta fibrillization in Alzheimer’s disease (AD). Here, we characterized the TTR/A-Beta interaction by competition binding assays. TTR binds to different A-Beta peptide species: soluble (Kd, 28nM), oligomers and fibrils; diverse TTR variants bind differentially to A-Beta. Transmission electron microscopy (TEM) analysis demonstrated that TTR is capable of interfering with A-Beta fibrillization by both inhibiting and disrupting fibril formation. Co-incubation of the two molecules resulted in the abolishment of A-Beta toxicity. Our results confirmed TTR as an A-Beta ligand and indicated the inhibition/disruption of A-Beta fibrils as a possible mechanism underlying the protective role of TTR in AD.

Abbreviations: AD, Alzheimer’s disease, WT TTR, wild-type transthyretin, V30M TTR, transthyretin with a valine substitute by a methionine at position 30, L55P TTR, transthyretin with a leucine substitute by a praline at position 55, Y78F TTR, transthyretin with a tyrosine substituted by a phenylalanine at position 78, T119M TTR, transthyretin with a threonine substituted by a methionine at position 119

Keywords: Alzheimer’s disease, A-Beta peptide, Transthyretin, Inhibitor, Disrupter, Neuroprotector

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PII: S0014-5793(08)00142-7

doi:10.1016/j.febslet.2008.02.034

FEBS Letters
Volume 582, Issue 6 , Pages 936-942, 19 March 2008

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