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Transthyretin binding to A-Beta peptide--impact on A-Beta fibrillogenesis and toxicity |
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| Authors: | Costa R Gonçalves A Saraiva M J Cardoso I |
| Institution: | a Molecular Neurobiology Unit, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre, 823, 4150-180 Porto, Portugal b ICBAS, University of Porto, Porto, Portugal |
| 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, 28 nM), 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. |
| Keywords: | AD Alzheimer&rsquo 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 |
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