γ-Oryzanol mitigates oxidative stress and prevents mutant SOD1-Related neurotoxicity in Drosophila and cell models of amyotrophic lateral sclerosis.
Oxidative stress plays a critical role in mutant copper/zinc superoxide dismutase 1 (SOD1)-linked amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by selective loss of motor neurons. Thus, an anti-oxidative stress remedy might be a promising means for the treatment of ALS. The aim of the present study is to investigate the neuroprotective effects of γ-oryzanol (Orz) and elucidate its relevant molecular mechanisms in mutant hSOD1-linked Drosophila and cell models of ALS. Orz treatment provided neuroprotection in flies with expression of hSOD1-G85R in motor neurons, as demonstrated by the prolonged survival, improvement of motor deficits, reduced oxidative damage and regulated redox homeostasis when compared with those in controls. Moreover, Orz significantly decreased neuronal apoptosis and upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutamate-cysteine ligase catalytic subunit (GCLC) antioxidant pathway via activating Akt in hSOD1-G93A-expressing NSC-34 cells. In addition, our results showed that both in vivo and in vitro, Akt served as an upstream regulator of signal transducers and activators of transcription (Stat) 3 stimulated by Orz, which further increased the level of another anti-oxidative stress factor heat-shock protein 70 (HSP70). Altogether, these findings provide evidence that Orz has potential neuroprotective effects that may be beneficial in the treatment of ALS disease with SOD1 mutations.
['Zhang|Chunting|C|', 'Liang|Weiwei|W|', 'Wang|Hongyong|H|', 'Yang|Yueqing|Y|', 'Wang|Tianhang|T|', 'Wang|Shuyu|S|', 'Wang|Xudong|X|', 'Wang|Ying|Y|', 'Feng|Honglin|H|']
D000690:Amyotrophic Lateral Sclerosis D000818:Animals D000975:Antioxidants D002460:Cell Line D004195:Disease Models, Animal D004330:Drosophila D029721:Drosophila Proteins D006801:Humans D008297:Male D051379:Mice D009046:Motor Neurons D009154:Mutation D018696:Neuroprotective Agents D018384:Oxidative Stress D010666:Phenylpropionates D013482:Superoxide Dismutase D000072105:Superoxide Dismutase-1
γ-Oryzanol Oxidative stress ALS Neuroprotection Akt SOD1