Cystatin C reduces the in vitro formation of soluble Abeta1-42 oligomers and protofibrils.
Scand J Clin Lab Invest
; 67(2): 179-90, 2007.
Article
em En
| MEDLINE
| ID: mdl-17365997
ABSTRACT
There are an increasing number of genetic and neuropathological observations to suggest that cystatin C, an extracellular protein produced by all nucleated cells, might play a role in the pathophysiology of sporadic Alzheimer's disease (AD). Recent observations indicate that small and large soluble oligomers of the beta-amyloid protein (Abeta) impair synaptic plasticity and induce neurotoxicity in AD. The objective of the present study was to investigate the influence of cystatin C on the production of such oligomers in vitro. Co-incubation of cystatin C with monomeric Abeta1-42 significantly attenuated the in vitro formation of Abeta oligomers and protofibrils, as determined using electron microscopy (EM), dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, thioflavin T (ThT) spectrofluorimetry and gel chromatography. However, cystatin C did not dissolve preformed Abeta oligomers. Direct binding of cystatin C to Abeta was demonstrated with the formation of an initial 11 molar high-affinity complex. These observations suggest that cystatin C might be a regulating element in the transformation of monomeric Abeta to larger and perhaps more toxic molecular species in vivo.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Inibidores de Proteases
/
Cistatinas
/
Peptídeos beta-Amiloides
Limite:
Animals
Idioma:
En
Revista:
Scand J Clin Lab Invest
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Dinamarca