title: Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway.
abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224, USA.
authors.forename: Tae Gen
authors.initials: TG
authors.lastname: Son
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Kawamoto
authors.forename: Qian-Sheng
authors.initials: QS
authors.lastname: Yu
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Simonetta
authors.initials: S
authors.lastname: Camandola
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D018698:Glutamic Acid / Q000009:adverse effects*; D056945:Hep G2 Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D061251:Primary Cell Culture; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013049:Spectrin
chemical_list: D002352:Carrier Proteins; D018698:Glutamic Acid; D008840:Microfilament Proteins; D051267:NF-E2-Related Factor 2; D009285:Naphthoquinones; D018696:Neuroprotective Agents; D013049:Spectrin; C495635:NFE2L2 protein, human; C495637:Nfe2l2 protein, rat; C005503:naphthazarin; C014758:plumbagin
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