Anti-amyloid activity of the C-terminal domain of proSP-C against amyloid beta-peptide and medin.
Biochemistry
; 48(17): 3778-86, 2009 May 05.
Article
em En
| MEDLINE
| ID: mdl-19281242
ABSTRACT
Amyloid fibrils are found in approximately 25 different diseases, including Alzheimer's disease. Lung surfactant protein C (SP-C) forms fibrils in association with pulmonary disease. It was recently found that the C-terminal domain of proSP-C (CTC), which is localized to the endoplasmic reticulum (ER) lumen, protects the transmembrane (TM) part of (pro)SP-C from aggregation into amyloid until it has a folded into an alpha-helix. CTC appears to have a more general anti-amyloid effect by also acting on TM regions of other proteins. Here we investigate interactions of CTC with the amyloid beta-peptide (Abeta) associated with Alzheimer's disease and medin, a peptide that forms fibrils in the most common form of human amyloid. CTC prevents fibril formation in Abeta and medin and forms a complex with Abeta oligomers, as judged by size-exclusion chromatography and electrospray ionization mass spectrometry. These data suggest that CTC functions as a chaperone that acts preferentially against unfolded TM segments and structural motifs found during amyloid fibril formation, a mechanism that may be exploited in forming a basis for future anti-amyloid therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Precursores de Proteínas
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Peptídeos beta-Amiloides
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Proteína C Associada a Surfactante Pulmonar
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Proteínas do Leite
Limite:
Humans
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Suécia