Nerelius, Charlotte
- Department of Molecular Biosciences, Swedish University of Agricultural Sciences
Abstract
Alzheimer disease is characterized by extracellular plaques composed of A beta peptides. We show here that these plaques also contain the serine protease inhibitor neuroserpin and that neuroserpin forms a 1:1 binary complex with the N-terminal or middle parts of the A beta(1-42) peptide. This complex inactivates neuroserpin as an inhibitor of tissue plasminogen activator and blocks the loop-sheet polymerization process that is characteristic of members of the serpin superfamily. In contrast neuroserpin accelerates the aggregation of A beta(1-42) with the resulting species having an appearance that is distinct from the mature amyloid fibril. Neuroserpin reduces the cytotoxicity of A beta(1-42) when assessed using standard cell assays, and the interaction has been confirmed in vivo in novel Drosophila models of disease. Taken together, these data show that neuroserpin interacts with A beta(1-42) to form off-pathway non-toxic oligomers and so protects neurons in Alzheimer disease.
Published in
Journal of Biological Chemistry
2006, volume: 281, number: 39, pages: 29268-29277
SLU Authors
Johansson, Jan
- Department of Molecular Biosciences, Swedish University of Agricultural Sciences
- Department of Molecular Biosciences, Swedish University of Agricultural Sciences
UKÄ Subject classification
Veterinary Science
Animal and Dairy Science
Publication identifier
- DOI: https://doi.org/10.1074/jbc.M600690200
Permanent link to this page (URI)
https://res.slu.se/id/publ/10599