Diammonium glycyrrhizinate upregulates PGC-1α and protects against Aß1-42-induced neurotoxicity.
PLoS One
; 7(4): e35823, 2012.
Article
em En
| MEDLINE
| ID: mdl-22540007
Mitochondrial dysfunction is a hallmark of beta-amyloid (Aß)-induced neurotoxicity in Alzheimer's disease (AD), and is considered an early event in AD pathology. Diammonium glycyrrhizinate (DG), the salt form of Glycyrrhizin, is known for its anti-inflammatory effects, resistance to biologic oxidation and membranous protection. In the present study, the neuroprotective effects of DG on Aß(1-42)-induced toxicity and its potential mechanisms in primary cortical neurons were investigated. Exposure of neurons to 2 µM Aß(1-42) resulted in significant viability loss and cell apoptosis. Accumulation of reactive oxygen species (ROS), decreased mitochondrial membrane potential, and activation of caspase-9 and caspase-3 were also observed after Aß(1-42) exposure. All these effects induced by Aß(1-42) were markedly reversed by DG treatment. In addition, DG could alleviate lipid peroxidation and partially restore the mitochondrial function in Aß(1-42)-induced AD mice. DG also significantly increased the PGC-1α expression in vivo and in vitro, while knocking down PGC-1α partially blocked the protective effects, which indicated that PGC-1α contributed to the neuroprotective effects of DG. Furthermore, DG significantly decreased the escape latency and search distance and increased the target crossing times of Aß(1-42)-induced AD mice in the Morris water maze test. Therefore, these results demonstrated that DG could attenuate Aß(1-42)-induced neuronal injury by preventing mitochondrial dysfunction and oxidative stress and improved cognitive impairment in Aß(1-42)-induced AD mice, indicating that DG exerted potential beneficial effects on AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Transativadores
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Peptídeos beta-Amiloides
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Fármacos Neuroprotetores
/
Ácido Glicirrízico
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article