title: Evaluation of longevity enhancing compounds against transactive response DNA-binding protein-43 neuronal toxicity.
abstract: In simple systems, lifespan can be extended by various methods including dietary restriction, mutations in the insulin/insulin-like growth factor (IGF) pathway or mitochondria among other processes. It is widely held that the mechanisms that extend lifespan may be adapted for diminishing age-associated pathologies. We tested whether a number of compounds reported to extend lifespan in C. elegans could reduce age-dependent toxicity caused by mutant TAR DNA-binding protein-43 in C. elegans motor neurons. Only half of the compounds tested show protective properties against neurodegeneration, suggesting that extended lifespan is not a strong predictor for neuroprotective properties. We report here that resveratrol, rolipram, reserpine, trolox, propyl gallate, and ethosuximide protect against mutant TAR DNA-binding protein-43 neuronal toxicity. Finally, of all the compounds tested, only resveratrol required daf-16 and sir-2.1 for protection, and ethosuximide showed dependence on daf-16 for its activity.
authors.affiliation: CRCHUM, Montréal, Québec, Canada.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Tauffenberger
authors.forename: Carl
authors.initials: C
authors.lastname: Julien
authors.forename: J Alex
authors.initials: JA
authors.lastname: Parker
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology*; D002839:Chromans / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005013:Ethosuximide / Q000493:pharmacokinetics*; D008136:Longevity / Q000187:drug effects* / Q000235:genetics*; D009046:Motor Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D011435:Propyl Gallate / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology*; D000077185:Resveratrol; D020889:Rolipram / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D002839:Chromans; D004268:DNA-Binding Proteins; D018696:Neuroprotective Agents; D013267:Stilbenes; D005013:Ethosuximide; D012110:Reserpine; D011435:Propyl Gallate; D020889:Rolipram; D000077185:Resveratrol; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid