A novel compound VSC2 has anti-inflammatory and antioxidant properties in microglia and in Parkinson's disease animal model.
Br J Pharmacol
; 172(4): 1087-100, 2015 Feb.
Article
de En
| MEDLINE
| ID: mdl-25297649
ABSTRACT
BACKGROUND AND PURPOSE:
Neuroinflammation through microglial activation is involved in the pathogenesis of neurodegenerative diseases including Parkinson's disease (PD), a major neurodegenerative disorder characterized by dopaminergic neuronal death in the substantia nigra. We examined our novel synthetic compound VSC2 for its anti-inflammatory properties towards development of a PD therapy. EXPERIMENTALAPPROACH:
We tested the effects of VSC2 on production of various NF-κB-dependent proinflammatory molecules and Nrf2-dependent antioxidant enzymes in BV-2 microglia and in vivo. KEYRESULTS:
The vinyl sulfone compound, VSC2, most effectively suppressed the production of NO in LPS-activated microglia. It also down-regulated expression of inducible NOS (iNOS), COX-2, IL-1ß and TNF-α and inhibited nuclear translocalization and transcriptional activity of NF-κB. VSC2 increased total and nuclear Nrf2 levels, induced Nrf2 transcriptional activity and was bound to Keap1 with high affinity. Expression of the Nrf2-regulated antioxidant enzyme genes NAD(P)H quinone oxidoreducase-1 (NQO-1), haem oxygenase-1 (HO-1) and glutamylcysteine ligase (GCL) were up-regulated by VSC2. In the MPTP mouse model of PD, oral administration of VSC2 decreased the number of activated microglia in the substantia nigra, lowered the levels of iNOS, COX-2 and IL-1ß, and protected the dopaminergic neurons. VSC2 also elevated the levels of NQO1, HO-1, GCL and Nrf2 in the nigrostriatal area. CONCLUSIONS AND IMPLICATIONS VSC2 has both anti-inflammatory and antioxidant properties and prevented neuroinflammation in microglia and in an animal model of PD. This suggests VSC2 as a potential candidate for PD therapy.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladie de Parkinson
/
Sulfones
/
Composés vinyliques
/
Microglie
/
Anti-inflammatoires
/
Antioxydants
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Br J Pharmacol
Année:
2015
Type de document:
Article
Pays d'affiliation:
Corée du Sud