TY - JOUR
T1 - FDA-approved drugs that protect mammalian neurons from glucose toxicity slow aging dependent on Cbp and protect against proteotoxicity
AU - Lublin, Alex
AU - Isoda, Fumiko
AU - Patel, Harshil
AU - Yen, Kelvin
AU - Nguyen, Linda
AU - Hajje, Daher
AU - Schwartz, Marc
AU - Mobbs, Charles
N1 - Funding Information:
All strains were obtained from the Caenorhabditis Genetics Center, funded by the NIH National Center for Research Resources (NCRR), and maintained at 20° C, under standard conditions . Strain CL2006, dvIs2[pCL12(unc-54/human Abeta peptide 1-42 minigene) + pRF4], used as a model for proteotoxicity in Alzheimer's disease, was created by Chris Link .
PY - 2011/11/16
Y1 - 2011/11/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=81155134279&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0027762
DO - 10.1371/journal.pone.0027762
M3 - Article
C2 - 22114686
AN - SCOPUS:81155134279
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e27762
ER -