Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment
  • Atiq, A.
  • Lee, H.J.
  • Khan, A.
  • Kang, M.H.
  • Rehman, I.U.
  • ... Kim, M.O.
  • 외 5명
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초록

Trolox is a potent antioxidant and a water-soluble analog of vitamin E. It has been used in scientific studies to examine oxidative stress and its impact on biological systems. Trolox has been shown to have a neuroprotective effect against ischemia and IL-1β-mediated neurodegeneration. In this study, we investigated the potential protective mechanisms of Trolox against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease mouse model. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of trolox against neuroinflammation, the oxidative stress mediated by MPTP in the Parkinson’s disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25–30 g). Our study showed that MPTP increased the expression of α-synuclein, decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, Trolox treatment significantly reversed these PD-like pathologies. Furthermore, Trolox treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Lastly, Trolox treatment inhibited the activated astrocytes (GFAP) and microglia (Iba-1), also reducing phosphorylated nuclear factor-κB, (p-NF-κB) and tumor necrosis factor-alpha (TNF-α) in the PD mouse brain. Overall, our study demonstrated that Trolox may exert neuroprotection on dopaminergic neurons against MPTP-induced oxidative stress, neuroinflammation, motor dysfunction, and neurodegeneration. © 2023 by the authors.

키워드

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)neurodegenerationneuroinflammationoxidative stresssubstantia nigra pars compacta (SNpc)trolox
제목
Vitamin E Analog Trolox Attenuates MPTP-Induced Parkinson’s Disease in Mice, Mitigating Oxidative Stress, Neuroinflammation, and Motor Impairment
저자
Atiq, A.Lee, H.J.Khan, A.Kang, M.H.Rehman, I.U.Ahmad, R.Tahir, M.Ali, J.Choe, K.Park, J.S.Kim, M.O.
DOI
10.3390/ijms24129942
발행일
2023-06
유형
Article
저널명
International Journal of Molecular Sciences
24
12