gamma-Secretase as a target for drug intervention in Alzheimer's disease.
Curr Opin Drug Discov Devel
; 7(5): 709-19, 2004 Sep.
Article
em En
| MEDLINE
| ID: mdl-15503873
gamma-Secretase is a critical enzyme involved in the production of amyloid-beta (Abeta) peptide, one of the main pathological hallmarks of Alzheimer's disease. gamma-Secretase cleaves the beta-amyloid precursor protein (betaAPP) at a position predicted to be within the membrane. In addition to betaAPP, gamma-secretase cleaves a range of other substrates. Thus, a key question in the development of gamma-secretase inhibitors for preventing Abeta production is whether undesired mechanism-based side effects may result from inhibition of cleavage of other substrates, and if so whether a suitable window exists to reduce brain Abeta. In this review, progress in the development of small-molecule inhibitors will be described, and potential toxicity issues associated with the development of gamma-secretase inhibitors discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endopeptidases
/
Inibidores de Proteases
/
Precursor de Proteína beta-Amiloide
/
Doença de Alzheimer
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article