biostudies-literatureUnknown7(1)Farina FHelping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown. Using drug screening in C. elegans nematodes with neuronal expression of human exon-1 huntingtin (128Q), we found that 3ß-Methoxy-Pregnenolone (MAP4343), 17ß-oestradiol (17ßE2) and 12 flavonoids including isoquercitrin promote neuronal fScientific reports4014https://www.ebi.ac.uk/biostudies/studies/S-EPMC5479833biostudies-literatureThe stress response factor daf-16/FOXO is required for multiple compound families to prolong the function of neurons with Huntington's disease.PMC5479833Verny MBaulieu EEParker JABoddaert JLejeune FXFarina FCommeau LRoudier NLambert EFonte CNeri CfalseThe stress response factor daf-16/FOXO is required for multiple compound families to prolong the function of neurons with Huntington's disease.Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown. Using drug screening in C. elegans nematodes with neuronal expression of human exon-1 huntingtin (128Q), we found that 3ß-Methoxy-Pregnenolone (MAP4343), 17ß-oestradiol (17ßE2) and 12 flavonoids including isoquercitrin promote neuronal f2017-01-01T00:00:00Z2017 Jun2025-04-05T14:22:58.258Z2019-03-27T02:48:11ZS-EPMC54798332863807810.1038/s41598-017-04256-w