Journal Article

FDA-Approved Drugs that Protect Mammalian Neurons from Glucose Toxicity Slow Aging Dependent on Cbp and Protect Against Proteotoxicity

Mobbs, Charles, Isoda, Fumiko, Yen, Kelvin, Nguyen, Linda, Hajje, Daher, Lublin, Alex, Patel, Harshil, Schwartz, Marc

2011

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acetaminophen / Acids / Adults / Age / Aging / Aging - drug effects / Alzheimer Disease - chemically induced / Alzheimer Disease - genetics / Alzheimer Disease - prevention & control / Alzheimer's disease / Alzheimers disease / Analgesics / Animals / Animals, Genetically Modified / Antibacterial agents / Bacitracin / Biology / Caenorhabditis elegans / Caenorhabditis elegans - genetics / Caenorhabditis elegans - growth & development / Caenorhabditis elegans - metabolism / Caenorhabditis elegans Proteins - antagonists & inhibitors / Caenorhabditis elegans Proteins - genetics / Caenorhabditis elegans Proteins - metabolism / Caffeine / Cell cycle / Complications / Dementia / Diabetes mellitus / Diet / Dietary restrictions / Disease Models, Animal / Drug Approval / Drug dosages / Drug screening / Drugs / Forkhead Transcription Factors / Genetic engineering / Glucose / Glucose - toxicity / Health aspects / Histone Acetyltransferases - antagonists & inhibitors / Histone Acetyltransferases - genetics / Histone Acetyltransferases - metabolism / Humans / Kinases / Lead compounds / Life span / Mammals / Medical treatment / Medicine / Metabolites / Mortality / Nematodes / Neurobiology / Neurodegenerative diseases / Neurons / Neurons - cytology / Neurons - drug effects / Neurosciences / Oxidative stress / Parkinson's disease / Parkinsons disease / Pharmaceutical Preparations - administration & dosage / Proteins / RNA, Small Interfering - genetics / RNA-mediated interference / Safety / Screening / Senescence / Signal Transduction - drug effects / Survival Rate / Tannic acid / Toxicity / Transcription Factors - antagonists & inhibitors / Transcription Factors - genetics / Transcription Factors - metabolism / Transgenic / United States / United States Food and Drug Administration