Abstract Title:

Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway.

Abstract Source:

Mol Med Rep. 2015 Dec 8. Epub 2015 Dec 8. PMID: 26648392

Abstract Author(s):

Qunli Cui, Xin Li, Hongcan Zhu

Article Affiliation:

Qunli Cui


Parkinson's disease (PD) is an age‑related complex neurodegenerative disease that affects ≤80% of dopaminergic neurons in the substantia nigra pars compacta (SNpc). It has previously been suggested that mitochondrial dysfunction, oxidative stress and oxidative damage underlie the pathogenesis of PD. Curcumin, which is a major active polyphenol component extracted from the rhizomes of Curcuma longa (Zingiberaceae), has been reported to exert neuroprotective effects on an experimental model of PD. The present study conducted a series of in vivo experiments, in order to investigate the effects of curcumin on behavioral deficits, oxidative damage and related mechanisms. The results demonstrated that curcumin was able to significantly alleviate motor dysfunction and increase suppressed tyrosine hydroxylase (TH) activity in the SNpc of rotenone (ROT)‑injured rats. Biochemical measurements indicated that rats pretreatedwith curcumin exhibited increased glutathione (GSH) levels, and reduced reactive oxygen species activity and malondialdehyde content. Mechanistic studies demonstrated that curcumin significantly restored the expression levels of heme oxygenase‑1 and NAD(P)H:quinone oxidoreductase 1, thus ameliorating ROT‑induced damage in vivo, via the phosphorylation of Akt and nuclear factor erythroid 2‑related factor 2 (Nrf2). Further studies indicated that the Akt/Nrf2 signaling pathway was associated with the protective role of curcumin in ROT‑treated rats. Inhibiting the Akt/Nrf2 pathway using a lentiviral vector containing Nrf2‑specific short hairpin RNA, or the phosphoinositide 3‑kinase inhibitor LY294002, markedly reduced the expression levels of TH and GSH, ultimately attenuating the neuroprotective effects of curcumin against oxidative damage. These results indicated that curcumin was able to significantly ameliorate ROT‑induced dopaminergic neuronal oxidative damage in the SNpc of rats via activation of the Akt/Nrf2 signaling pathway.

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