title: Decaffeinated coffee and nicotine-free tobacco provide neuroprotection in Drosophila models of Parkinson's disease through an NRF2-dependent mechanism.
abstract: Epidemiological studies have revealed a significantly reduced risk of Parkinson's disease (PD) among coffee and tobacco users, although it is unclear whether these correlations reflect neuroprotective/symptomatic effects of these agents or preexisting differences in the brains of tobacco and coffee users. Here, we report that coffee and tobacco, but not caffeine or nicotine, are neuroprotective in fly PD models. We further report that decaffeinated coffee and nicotine-free tobacco are as neuroprotective as their caffeine and nicotine-containing counterparts and that the neuroprotective effects of decaffeinated coffee and nicotine-free tobacco are also evident in Drosophila models of Alzheimer's disease and polyglutamine disease. Finally, we report that the neuroprotective effects of decaffeinated coffee and nicotine-free tobacco require the cytoprotective transcription factor Nrf2 and that a known Nrf2 activator in coffee, cafestol, is also able to confer neuroprotection in our fly models of PD. Our findings indicate that coffee and tobacco contain Nrf2-activating compounds that may account for the reduced risk of PD among coffee and tobacco users. These compounds represent attractive candidates for therapeutic intervention in PD and perhaps other neurodegenerative diseases.
authors.affiliation: Department of Genome Sciences and Chemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Kien
authors.initials: K
authors.lastname: Trinh
authors.forename: Laurie
authors.initials: L
authors.lastname: Andrews
authors.forename: James
authors.initials: J
authors.lastname: Krause
authors.forename: Tyler
authors.initials: T
authors.lastname: Hanak
authors.forename: Daewoo
authors.initials: D
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Gelb
authors.forename: Leo
authors.initials: L
authors.lastname: Pallanck
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002110:Caffeine / Q000302:isolation & purification; D002478:Cells, Cultured; D003069:Coffee; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D009538:Nicotine / Q000302:isolation & purification; D010300:Parkinson Disease / Q000378:metabolism / Q000517:prevention & control*; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use; D014026:Nicotiana
chemical_list: D003069:Coffee; D004224:Diterpenes; D029721:Drosophila Proteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D010936:Plant Extracts; D002110:Caffeine; D009538:Nicotine; C053400:cafestol
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