Cysteine protease inhibitors reduce brain beta-amyloid and beta-secretase activity in vivo and are potential Alzheimer's disease therapeutics.
Biol Chem
; 388(9): 979-83, 2007 Sep.
Article
em En
| MEDLINE
| ID: mdl-17696783
ABSTRACT
Beta-secretase inhibitors that lower brain beta-amyloid peptides (Abeta) are likely to be effective for treating Alzheimer's disease (AD). Irreversible epoxysuccinyl cysteine protease inhibitors are known to reduce brain Abeta and beta-secretase activity in the guinea pig model of human Abeta production. In this study, acetyl-L-leucyl-L-valyl-L-lysinal (Ac-LVK-CHO) is also shown to significantly reduce brain Abeta and beta-secretase activity and brain Abeta in the same model. Ac-LVK-CHO is structurally distinct from the epoxysuccinyl inhibitors and is a reversible cysteine protease inhibitor. The results suggest that cysteine protease inhibitors generally, and reversible cysteine protease inhibitors specifically, have potential for development as AD therapeutics.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Encéfalo
/
Cisteína Endopeptidases
/
Catepsina B
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Catepsinas
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Inibidores de Cisteína Proteinase
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Peptídeos beta-Amiloides
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Secretases da Proteína Precursora do Amiloide
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Doença de Alzheimer
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article