Genetic Mechanisms of Coffee Extract Protection in aCaenorhabditis elegansModel of β-Amyloid Peptide Toxicity
- 1 November 2010
- journal article
- Published by Oxford University Press (OUP) in Genetics
- Vol. 186 (3), 857-866
- https://doi.org/10.1534/genetics.110.120436
Abstract
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.Keywords
This publication has 47 references indexed in Scilit:
- Nuclear Erythroid Factor 2-mediated Proteasome Activation Delays Senescence in Human FibroblastsOnline Journal of Public Health Informatics, 2010
- Life‐span extension by dietary restriction is mediated by NLP‐7 signaling and coelomocyte endocytosis inC. elegansThe FASEB Journal, 2009
- Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer's diseaseProceedings of the National Academy of Sciences of the United States of America, 2009
- AIP-1 ameliorates β-amyloid peptide toxicity in a Caenorhabditis elegans Alzheimer's disease modelHuman Molecular Genetics, 2009
- Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: Critical role for the astrocyteProceedings of the National Academy of Sciences of the United States of America, 2009
- Nrf2 signaling: An adaptive response pathway for protection against environmental toxic insultsMutation Research - Reviews in Mutation Research, 2008
- Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf‐1‐dependent mechanism in Caenorhabditis elegansAging Cell, 2008
- Activation of SKN-1 by novel kinases in Caenorhabditis elegansFree Radical Biology & Medicine, 2007
- Systematic functional analysis of the Caenorhabditis elegans genome using RNAiNature, 2003
- IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNANature, 2002