Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Aβ protofibrils

被引：194

作者：

Habicht, Gernot ^{[2
]}

Haupt, Christian ^{[1
]}

Friedrich, Ralf P.

Hortschansky, Peter ^{[2
]}

Sachse, Carsten ^{[1
]}

Meinhardt, Jessica ^{[1
]}

Wieligmann, Karin ^{[1
]}

Gellermann, Gerald P. ^{[1
]}

Brodhun, Michael ^{[3
]}

Goetz, Juergen ^{[4
]}

Halbhuber, Karl-Juergen ^{[5
]}

Roecken, Christoph ^{[6
]}

Horn, Uwe ^{[2
]}

Faendrich, Marcus ^{[1
]}

机构：

[1] Fritz Lipmann Inst, Leibniz Inst Alterforsch, D-07745 Jena, Germany

[2] Hans Knoell Inst, Leibniz Inst Nat Stoff Forsch & Infekt Biol, D-07745 Jena, Germany

[3] Univ Jena, Inst Pathol, D-07740 Jena, Germany

[4] Univ Sydney, Alzheimers & Parkinsons Dis Lab, Brain & Mind Res Inst, Camperdown, NSW 2050, Australia

[5] Univ Jena, Inst Anat 2, D-07743 Jena, Germany

[6] Charite Univ Med Berlin, Inst Pathol, D-10117 Berlin, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 49期

关键词：

neurodegeneration; prion; protein folding;

D O I：

10.1073/pnas.0703793104

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

The formation of amyloid fibrils is a common biochemical characteristic that occurs in Alzheimer's disease and several other amyloidoses. The unifying structural feature of amyloid fibrils is their specific type of beta-sheet conformation that differentiates these fibrils from the products of normal protein folding reactions. Here we describe the generation of an antibody domain, termed B10, that recognizes an amyloid-specific and conformationally defined epitope. This antibody domain was selected by phage-display from a recombinant library of camelid antibody domains. Surface plasmon resonance, immunoblots, and immunohistochemistry show that this antibody domain distinguishes A beta amyloid fibrils from disaggregated A beta peptide as well as from specific A beta oligomers. The antibody domain possesses functional activity in preventing the formation of mature amyloid fibrils by stabilizing A beta protofibrils. These data suggest possible applications of B10 in the detection of amyloid fibrils or in the modulation of their formation.

引用

页码：19232 / 19237

页数：6

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