title: FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on cbp and protect against proteotoxicity.
abstract: Screening a library of drugs with known safety profiles in humans yielded 30 drugs that reliably protected mammalian neurons against glucose toxicity. Subsequent screening demonstrated that 6 of these 30 drugs increase lifespan in C. elegans: caffeine, ciclopirox olamine, tannic acid, acetaminophen, bacitracin, and baicalein. Every drug significantly reduced the age-dependent acceleration of mortality rate. These protective effects were blocked by RNAi inhibition of cbp-1 in adults only, which also blocks protective effects of dietary restriction. Only 2 drugs, caffeine and tannic acid, exhibited a similar dependency on DAF-16. Caffeine, tannic acid, and bacitracin also reduced pathology in a transgenic model of proteotoxicity associated with Alzheimer's disease. These results further support a key role for glucose toxicity in driving age-related pathologies and for CBP-1 in protection against age-related pathologies. These results also provide novel lead compounds with known safety profiles in human for treatment of age-related diseases, including Alzheimer's disease and diabetic complications.
authors: Fishberg Center for Neurobiology, Mount Sinai School of Medicine, New York, New York, United States of America.
authors: Alex
authors: A
authors: Lublin
authors: Fumiko
authors: F
authors: Isoda
authors: Harshil
authors: H
authors: Patel
authors: Kelvin
authors: K
authors: Yen
authors: Linda
authors: L
authors: Nguyen
authors: Daher
authors: D
authors: Hajje
authors: Marc
authors: M
authors: Schwartz
authors: Charles
authors: C
authors: Mobbs
mesh_terms: D000375:Aging / Q000187:drug effects*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017277:Drug Approval; D051858:Forkhead Transcription Factors; D005947:Glucose / Q000633:toxicity*; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D004364:Pharmaceutical Preparations; D034741:RNA, Small Interfering; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C111709:CBP-1 protein, C elegans; D051548:Histone Acetyltransferases; D005947:Glucose