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

被引：121

作者：

Costa, R. ^{[1
]}

Goncalves, A. ^{[1
]}

Saralva, M. J. ^{[1
,2
]}

Cardoso, I. ^{[1
]}

机构：

[1] IBMC, Mol Neurobiol Unit, P-4150180 Oporto, Portugal

[2] Univ Porto, ICBAS, P-4100 Oporto, Portugal

来源：

FEBS LETTERS | 2008年 / 582卷 / 06期

关键词：

Alzheimer's disease; A-Beta peptide; transthyretin; inhibitor; disrupter; neuroprotector;

D O I：

10.1016/j.febslet.2008.02.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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收藏

页码：936 / 942

页数：7

相关论文

共 35 条

[1] Thyroxine binding to transthyretin Met 119 - Comparative studies of different heterozygotic carriers and structural analysis [J].

Almeida, MR ;

Damas, AM ;

Lans, MC ;

Brouwer, A ;

Saraiva, MJ .

ENDOCRINE, 1997, 6 (03) :309-315

[2] Comparative studies of two transthyretin variants with protective effects on familial amyloidotic polyneuropathy: TTR R104H and TTR T119M [J].

Almeida, MR ;

Alves, IL ;

Terazaki, H ;

Ando, Y ;

Saraiva, MJ .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 270 (03) :1024-1028

[3] Comparative stability and clearance of [Met30]transthyretin and [Met119]transthyretin [J].

Alves, IL ;

Hays, MT ;

Saraiva, MJM .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 249 (03) :662-668

[4] Alzheimer's disease: Neurodevelopment converges with neurodegeneration [J].

Bothwell, M ;

Giniger, E .

CELL, 2000, 102 (03) :271-273

[5] Transthyretin fibrillogenesis entails the assembly of monomers:: A molecular model for in vitro assembled transthyretin amyloid-like fibrils [J].

Cardoso, I ;

Goldsbury, CS ;

Müller, SA ;

Olivieri, V ;

Wirtz, S ;

Damas, AM ;

Aebi, U ;

Saraiva, MJ .

JOURNAL OF MOLECULAR BIOLOGY, 2002, 317 (05) :683-695

[6] Serum insulin-like growth factor I regulates brain amyloid-levels [J].

Carro, E ;

Trejo, JL ;

Gomez-Isla, T ;

LeRoith, D ;

Torres-Aleman, I .

NATURE MEDICINE, 2002, 8 (12) :1390-1397

[7] Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer's disease and non-demented elderly subjects [J].

Castaño, EM ;

Roher, AE ;

Esh, CL ;

Kokjohn, TA ;

Beach, T .

NEUROLOGICAL RESEARCH, 2006, 28 (02) :155-163

[8] Binding of gelsolin, a secretory protein, to amyloid β-protein [J].

Chauhan, VPS ;

Ray, I ;

Chauhan, A ;

Wisniewski, HM .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 258 (02) :241-246

[9] Accelerated Aβ deposition in APPswe/PS1ΔE9 mice with hemizygous deletions of TTR (transthyretin) [J].

Choi, Se Hoon ;

Leight, Susan N. ;

Lee, Virginia M. -Y. ;

Li, Tong ;

Wong, Philip C. ;

Johnson, Jeffrey A. ;

Saraiva, Maria J. ;

Sisodia, Sangram S. .

JOURNAL OF NEUROSCIENCE, 2007, 27 (26) :7006-7010

[10] Mechanisms of Aβ mediated neurodegeneration in Alzheimer's disease [J].

Crouch, Peter J. ;

Harding, Susan-Marie E. ;

White, Anthony R. ;

Camakaris, James ;

Bush, Ashley I. ;

Masters, Colin L. .

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (02) :181-198

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