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Gingerol‐Induced Hypoxia‐Inducible Factor 1 Alpha Inhibits Human Prion Peptide‐Mediated Neurotoxicity
Author(s) -
Jeong JaeKyo,
Moon MyungHee,
Park YangGyu,
Lee JuHee,
Lee YouJin,
Seol JaeWon,
Park SangYouel
Publication year - 2013
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.4842
Subject(s) - neuroprotection , neurotoxicity , neurodegeneration , scrapie , programmed cell death , mitochondrion , apoptosis , pharmacology , chemistry , microbiology and biotechnology , biology , biochemistry , medicine , toxicity , prion protein , pathology , disease , organic chemistry
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. Copyright © 2012 John Wiley & Sons, Ltd.