Abeta 1-42 induces mild endoplasmic reticulum stress in an aggregation state-dependent manner.
Antioxid Redox Signal
; 9(12): 2245-54, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17979527
ABSTRACT
Alzheimer's disease (AD) is characterized by the aggregation of misfolded proteins. Previously we reported activation of the unfolded protein response (UPR) in AD neurons. A potential source for UPR activation in AD neurons may be the increased levels of beta-amyloid (Abeta). In this study, we used preparations enriched in oligomeric or fibrillar Abeta (1-42) to investigate the role of the conformational state of Abeta in UPR activation in differentiated neuroblastoma cells. Both oligomeric and fibrillar Abeta (1-42) do not induce BiP expression to the extent that it can be detected in a pool of cells. However, using a fluorescent UPR reporter cell line that allows analysis of individual cells, we demonstrated mild activation of the UPR by oligomeric but not fibrillar Abeta (1-42). We showed that oligomeric Abeta (1-42) is significantly more toxic to cells primed for UPR than is fibrillar Abeta (1-42), indicating that activation of the UPR contributes to oligomer-specific Abeta (1-42) toxicity. Because UPR activation is observed in AD brain at a stage that precedes the massive fibrillar Abeta deposition and tangle formation, this may indicate a role for nonfibrillar Abeta in the induction of the UPR in AD neurons.
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Conformação Proteica
/
Estresse Fisiológico
/
Peptídeos beta-Amiloides
/
Retículo Endoplasmático
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article