Genetic mechanisms of coffee extract protection in a Caenorhabditis elegans model of β-amyloid peptide toxicity.
Epidemiological studies have reported that coffee and/or caffeine consumption may reduce Alzheimer's disease (AD) risk. We found that coffee extracts can similarly protect against β-amyloid peptide (Aβ) toxicity in a transgenic Caenorhabditis elegans Alzheimer's disease model. The primary protective component(s) in this model is not caffeine, although caffeine by itself can show moderate protection. Coffee exposure did not decrease Aβ transgene expression and did not need to be present during Aβ induction to convey protection, suggesting that coffee exposure protection might act by activating a protective pathway. By screening the effects of coffee on a series of transgenic C. elegans stress reporter strains, we identified activation of the skn-1 (Nrf2 in mammals) transcription factor as a potential mechanism of coffee extract protection. Inactivation of skn-1 genetically or by RNAi strongly blocked the protective effects of coffee extract, indicating that activation of the skn-1 pathway was the primary mechanism of coffee protection. Coffee also protected against toxicity resulting from an aggregating form of green fluorescent protein (GFP) in a skn-1-dependent manner. These results suggest that the reported protective effects of coffee in multiple neurodegenerative diseases may result from a general activation of the Nrf2 phase II detoxification pathway.
Dostal
Vishantie
V
Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado 80309, USA.
Roberts
Christine M
CM
Link
Christopher D
CD
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology / Q000627:therapeutic use; D031204:Caloric Restriction; D004268:DNA-Binding Proteins / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D023421:Models, Animal; D009068:Movement / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D010243:Paralysis / Q000188:drug therapy / Q000503:physiopathology; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D020836:Protein Structure, Quaternary; D014157:Transcription Factors / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D010936:Plant Extracts; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C073702:skn-1 protein, C elegans; D002110:Caffeine
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