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- W4290998801 abstract "Current treatments for Parkinson's Disease (PD) only provide symptomatic relief; however, they don't delay the disease progression, hence new treatment options should be considered. Carvedilol is a nonselective β & α1 blocker with additional effects as an antioxidant, anti-inflammatory and neuro protective properties. In this research, an insilico study was conducted to primarily evaluate carvedilol as an anti-parkinsonian and anti-tau protein target. PASS prediction was performed followed by a docking study of carvedilol. Carvedilol yielded promising results and forward guided this study onto its in vivo evaluation. The in vivo study aimed to assess the neuro-protective effects of carvedilol in rotenone-induced rat model of PD and investigate the potential underlying mechanisms. The effects of carvedilol (2.5, 5, and 10 mg/kg) on the measured parameters of open field, catalepsy, Y-maze tests as well as brain histology, and tyrosine hydroxylase (TH) were evaluated. The effective doses (5 and 10 mg/kg) were further tested for their potential anti-tau protein effects. Carvedilol (5 and 10 mg/kg) prevented rotenone-induced motor deficits, spatial memory dysfunction, and histological damage. Additionally, carvedilol significantly inhibited rotenone-induced decrease in TH expression in the striata of the rats. These effects were associated with reduction of rotenone-induced neuro-inflammation, microglial activation and release of glial fibrillary acidic protein (GFAP), along with reduction in N-methyl-D-aspartate receptors activation, alpha-synculein and phospho-Tau (P-Tau) protein expression. Carvedilol also reduced tau protein hyper-phosphosrylation by Glycogen synthase 3β (GSK 3β) inhibition and Phosphoinositide 3-kinase (PI3K) stimulation. Collectively, these results suggest that carvedilol might be a possible candidate for management of PD." @default.
- W4290998801 created "2022-08-13" @default.
- W4290998801 creator A5009050214 @default.
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- W4290998801 creator A5047803303 @default.
- W4290998801 creator A5047999427 @default.
- W4290998801 creator A5077241670 @default.
- W4290998801 date "2022-10-01" @default.
- W4290998801 modified "2023-09-27" @default.
- W4290998801 title "Neuroprotective repositioning and anti-tau effect of carvedilol on rotenone induced neurotoxicity in rats: Insights from an insilico& in vivo anti-Parkinson's disease study" @default.
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- W4290998801 doi "https://doi.org/10.1016/j.ejphar.2022.175204" @default.
- W4290998801 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35964655" @default.
- W4290998801 hasPublicationYear "2022" @default.