Neurotoxin ßNmethylaminoLalanine induces endoplasmic reticulum stressmediated neuronal apoptosis.
Mol Med Rep
; 14(5): 4873-4880, 2016 Nov.
Article
em En
| MEDLINE
| ID: mdl-27748814
ABSTRACT
ß-N-methylamino-L-alanine (BMAA) is a neurotoxin that is closely associated with the incidence of amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. In cultured neuronal cells, BMAA notably induces the upregulation of endoplasmic reticulum (ER) chaperons and activates the unfolded protein response (UPR) receptor pathways of protein kinase RNAlike endoplasmic reticulum kinase, inositolrequiring kinase 1 and transcription factor 6. The ER stressspecific protein CCAAT/enhancerbinding protein homologous protein (CHOP) affords proapoptotic responses that cause mitochondrial damage and caspase activation. BMAA also induces the activation of mitogenactivated protein kinase member cJUN Nterminal kinase, p38 and extracellular signalregulated kinase, which have been suggested to be involved in the signaling pathway of UPRmediated apoptosis. Inhibition of ER stress using ER stress antagonist, salubrinal, attenuated the expression of CHOP and alleviated neuronal death. Overexpression of heat shock protein 70 suppressed the activation of UPR receptors and UPRevoked apoptotic signaling. The present findings demonstrated that ER stress induced by BMAA is the important mediator of neuronal injury and apoptotic death, and suggests development in novel therapeutic strategies for treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse do Retículo Endoplasmático
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Diamino Aminoácidos
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Neurônios
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Neurotoxinas
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2016
Tipo de documento:
Article