Korea Zoonoses Research Institute, Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk, South Korea.
Phytother Res. 2013 Aug;27(8):1185-92. doi: 10.1002/ptr.4842. Epub 2012 Sep 25.
Prion diseases are a family member of neurodegenerative disorders caused by the accumulation of misfolded-prion proteins (scrapie form of PrP, PrP(Sc)). The accumulation of PrP(Sc) in the brain leads to neurotoxicity by the induction of mitochondrial-apoptotic pathways. Recent studies implicated gingerol in protection against neurodegeneration. However, the basis of the neuroprotection in prion disease remains unclear. Thus, we investigated the influence of gingerol on prion peptide-induced neuronal damage. Gingerol blocked PrP(106-126)-mediated neurotoxicity by protecting mitochondrial function. Moreover, the protective effect of gingerol against PrP(106-126)-induced mitochondrial damage was associated with hypoxia-inducible factor 1 alpha (HIF-1α) expression. Gingerol-induced HIF-1α expression inhibited the PrP(106-126)-induced mitochondrial dysfunction. On the other hand, inhibition of gingerol-induced HIF-1 α expression attenuated the gingerol-mediated neuroprotective effect. Here, we demonstrate for the first time that treatment with gingerol prevents prion peptide-mediated neuronal cell death and that the neuroprotection is induced by HIF-1α-mediated signals. This study suggests that treatment with gingerol may provide a novel therapeutic strategy for prion-mediated neurotoxicity.
朊病毒病是由错误折叠的朊病毒蛋白（瘙痒形式的 PrP，PrP(Sc)）积累引起的神经退行性疾病家族成员。脑内 PrP(Sc) 的积累通过诱导线粒体凋亡途径导致神经毒性。最近的研究表明姜辣素具有预防神经退行性变的作用。然而，朊病毒病中神经保护的基础仍不清楚。因此，我们研究了姜辣素对朊病毒肽诱导的神经元损伤的影响。姜辣素通过保护线粒体功能来阻断 PrP(106-126)介导的神经毒性。此外，姜辣素对 PrP(106-126)诱导的线粒体损伤的保护作用与低氧诱导因子 1α (HIF-1α)表达有关。姜辣素诱导的 HIF-1α表达抑制了 PrP(106-126)诱导的线粒体功能障碍。另一方面，抑制姜辣素诱导的 HIF-1α表达减弱了姜辣素介导的神经保护作用。本研究首次证明，姜辣素治疗可预防朊病毒肽介导的神经元细胞死亡，且神经保护作用是通过 HIF-1α介导的信号诱导的。本研究提示，姜辣素治疗可能为朊病毒介导的神经毒性提供一种新的治疗策略。
