期刊
PHYTOTHERAPY RESEARCH
卷 27, 期 8, 页码 1185-1192出版社
WILEY
DOI: 10.1002/ptr.4842
关键词
gingerol; PrP(106-126); HIF-1; prion disease
资金
- National Research Foundation of the Korea
- Korean Government [2012R1A1B3000463]
- National Research Foundation of Korea [2012R1A1B3000463] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Prion diseases are a family member of neurodegenerative disorders caused by the accumulation of misfolded-prion proteins (scrapie form of PrP, PrPSc). The accumulation of PrPSc 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-1) expression. Gingerol-induced HIF-1 expression inhibited the PrP(106-126)-induced mitochondrial dysfunction. On the other hand, inhibition of gingerol-induced HIF-1 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-1-mediated signals. This study suggests that treatment with gingerol may provide a novel therapeutic strategy for prion-mediated neurotoxicity. Copyright (c) 2012 John Wiley & Sons, Ltd.
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