期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 281, 期 39, 页码 29268-29277出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M600690200
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资金
- Medical Research Council [G0500306] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- Medical Research Council [G0500306] Funding Source: researchfish
- MRC [G0500306] Funding Source: UKRI
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.
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