Prevention of beta-amyloid neurotoxicity by blockade of the ubiquitin-proteasome proteolytic pathway.
J Neurochem
; 75(3): 1258-63, 2000 Sep.
Article
em En
| MEDLINE
| ID: mdl-10936209
ABSTRACT
In many neurodegenerative disorders, such as Alzheimer's disease, inclusions containing ubiquitinated proteins have been found in the brain, suggesting a pathophysiological role for ubiquitin-mediated proteasomal degradation of neuronal proteins. Here we show for the first time that the beta-amyloid fragment 1-40, which in micromolar levels causes the death of cortical neurons, also induces the ubiquitination of several neuronal proteins. Prevention of ubiquitination and inhibition of proteasome activity block the neurotoxic effect of beta-amyloid. These data suggest that beta-amyloid neurotoxicity may cause toxicity through the activation of protein degradation via the ubiquitin-proteasome pathway. These findings suggest possible new pharmacological targets for the prophylaxis and/or treatment of Alzheimer's disease and possibly for other related neurodegenerative disorders.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Acetilcisteína
/
Cisteína Endopeptidases
/
Ubiquitinas
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Peptídeos beta-Amiloides
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Complexos Multienzimáticos
/
Neurônios
/
Neurotoxinas
Limite:
Animals
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article