FDA-Approved Drugs that Protect Mammalian Neurons.ppt

FDA-Approved Drugs that Protect Mammalian Neuronsfrom Glucose Toxicity Slow Aging Dependent on Cbpand Protect Against Proteotoxicity PLoS ONE November 2011 Glucose Toxicity（葡萄糖毒性） Proteotoxicity（蛋白质毒性） Cbp（反应原件结合蛋白） Content Introduction Results Conclusion Discussion Introduction Interventions directed at fundamental processes of aging may mimic the broad protective effects of dietary restriction against age-related pathologies. We also hypothesized that the protective effects of such drugs would depend on CBP-1 and possibly DAF-16. Results The primary screen Utilizing dye-based assay for neurons viability The secondary screen Measuring lactate dehydrogenase released into the medium as a marker of cell death Caffeine increases lifespan and slows aging dependent on DAF-16 and CBP-1 and delays proteotoxicity Conclusion Conclusion We assessed protective effects of these drugs depend on CBP-1 Discussion A reduction in glucose toxicity mediates protective effects of dietary restriction during aging dependent on the activity of Cbp. Drugs which protect against glucose toxicity exhibit a remarkably high probability of increasing lifespan and reducing proteotoxicity. the present studies greatly extend the number of corroborated drugs that may protect against a wide range of age-related pathologies including diabetic complications, Alzheimer’s disease, and the rate of aging itself. * Increase lifespan in C.elegans Ciclopirox increases lifespan and slows aging, but does not delay proteotoxicity Tannic acid increases lifespan and slows aging dependent on DAF-16 and CBP-1 and delays proteotoxicity Acetaminophen increases lifespan dependent on CBP-1 and does not delay proteotoxicty Bacitracin increases lifespan dependent of CBP-1 and delays proteotoxcity Baicalein increases lifespan and slows aging dependent on CBP-1 but does not significantly delay proteotoxicity √ × × √ baicalein √ × √ √ bacitracin × × √ √ acetaminophen √ × × √ tannic acid × × √