Binding of proteases to fibrillar amyloid-beta protein and its inhibition by Congo red.
J Alzheimers Dis
; 12(3): 261-9, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-18057560
ABSTRACT
Fibrillar amyloid-beta protein (fAbeta) is the principal component of amyloid plaques in the brains of patients with Alzheimer's disease (AD). We have recently reported that activity of trypsin is inhibited by fAbeta and that trypsin can bind to fAbeta. Neprilysin and insulysin are important proteases for the clearance of soluble Abeta. Here, we report that fAbeta also binds to neprilysin and insulysin, which results in the inhibition of their proteolytic activities. These findings suggest that clearance of soluble Abeta may be defective in AD because of binding of proteases to amyloid plaques, leading to inactivation of proteases that are required for catabolism of Abeta. The identification of compounds that can inhibit binding of proteases to fAbeta may, therefore, be of significance for therapeutic intervention in AD. Congo red and Thioflavin T are widely used for histopathological examination of amyloid plaques because of their strong affinity to fibrillar amyloid proteins. We examined the effect of Congo red and Thioflavin T (potent fAbeta-binding compounds) on the binding of different proteases to fAbeta. While Congo red inhibited the binding of trypsin, neprilysin and insulysin to fAbeta, Thioflavin T did not have any effect. The effect of Congo red was concentration-dependent and the inhibitory effect was in the order of trypsin > insulysin > neprilysin. When the effect of prebound-Congo red to fAbeta was examined, trypsin was unable to bind to this complex suggesting that Congo red may have better affinity than trypsin for binding to fAbeta. Based on these results, we propose that the inhibition of binding of proteases to amyloid plaques may help in reducing the deposition of Abeta in AD.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Hidrolases
/
Peptídeos beta-Amiloides
/
Emaranhados Neurofibrilares
/
Vermelho Congo
/
Corantes
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article