Beta-secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice.
FASEB J
; 25(2): 775-84, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-21059748
ABSTRACT
Alzheimer disease is intimately linked to an excess amount of amyloid-ß (Aß) in the brain. Thus, therapeutic inhibition of Aß production is an attractive clinical approach to treat this disease. Here we provide the first direct experimental evidence that the treatment of Tg2576 transgenic mice with an inhibitor of ß-secretase, GRL-8234, rescues the age-related cognitive decline. We demonstrated that the injected GRL-8234 effectively enters the brain and rapidly decreases soluble Aß in the brain of Tg2576 mice. The rescue of cognition, which was observed only after long-term inhibitor treatment ranging from 5 to 7.5 mo, was associated with a decrease of brain amyloid-ß plaque load. We also found no accumulation of amyloid-ß precursor protein after several months of inhibitor treatment. These observations substantiate the idea that Aß accumulation plays a major role in the cognitive decline of Tg2576 mice and support the concept of Aß reduction therapy as a treatment of AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Ftálicos
/
Sulfonamidas
/
Precursor de Proteína beta-Amiloide
/
Secretases da Proteína Precursora do Amiloide
Limite:
Animals
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos