title: Gingerol-induced hypoxia-inducible factor 1 alpha inhibits human prion peptide-mediated neurotoxicity.
abstract: 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.
authors.affiliation: Korea Zoonoses Research Institute, Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk, South Korea.
authors.forename: Jae-Kyo
authors.initials: JK
authors.lastname: Jeong
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Moon
authors.forename: Yang-Gyu
authors.initials: YG
authors.lastname: Park
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Seol
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002396:Catechols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005233:Fatty Alcohols / Q000494:pharmacology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000009:adverse effects*; D011328:Prions / Q000009:adverse effects*
chemical_list: D002396:Catechols; D005233:Fatty Alcohols; D051793:Hypoxia-Inducible Factor 1; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126); C007845:gingerol