Worming our way to novel drug discovery with the Caenorhabditis elegans proteostasis network, stress response and insulin-signaling pathways

Bibliography

• Powers ET, Morimoto RI, Dillin A, et al. Biological and chemical approaches to diseases of proteostasis deficiency. Annu Rev Biochem 2009;78:959-91
   PubMed Web of Science ®Google Scholar
• Denny RA, Gavrin LK, Saiah E. Recent developments in targeting protein misfolding diseases. Bioorg Med Chem Lett 2013;23(7):1935-44
   PubMed Web of Science ®Google Scholar
• Westerheide SD, Bosman JD, Mbadugha BN, et al. Celastrols as inducers of the heat shock response and cytoprotection. J Biol Chem 2004;279(53):56053-60
   PubMed Web of Science ®Google Scholar
• Silverman GA, Pak SC, Perlmutter DH. Disorders of protein misfolding: alpha-1-antitrypsin deficiency as prototype. J Pediatr 2013;163(2):320-6
   PubMed Web of Science ®Google Scholar
• Cohen E, Dillin A. The insulin paradox: aging, proteotoxicity and neurodegeneration. Nat Rev Neurosci 2008;9(10):759-67
   PubMed Web of Science ®Google Scholar
• Florez-McClure ML, Hohsfield LA, Fonte G, et al. Decreased insulin-receptor signaling promotes the autophagic degradation of beta-amyloid peptide in C. elegans. Autophagy 2007;3(6):569-80
   PubMed Web of Science ®Google Scholar
• Boccitto M, Lamitina T, Kalb RG. Daf-2 signaling modifies mutant SOD1 toxicity in C. elegans. PLoS One 2012;7(3):e33494
   Google Scholar
• Cohen E, Bieschke J, Perciavalle RM, et al. Opposing activities protect against age-onset proteotoxicity. Science 2006;313(5793):1604-10
   PubMed Web of Science ®Google Scholar
• Cohen E, Paulsson JF, Blinder P, et al. Reduced IGF-1 signaling delays age-associated proteotoxicity in mice. Cell 2009;139(6):1157-69
   PubMed Web of Science ®Google Scholar
• Gosai SJ, Kwak JH, Luke CJ, et al. Automated high-content live animal drug screening using C. elegans expressing the aggregation prone serpin alpha1-antitrypsin Z. PLoS One 2010;5(11):e15460
   PubMed Web of Science ®Google Scholar
• Giacomotto J, Segalat L, Carre-Pierrat M, Gieseler K. Caenorhabditis elegans as a chemical screening tool for the study of neuromuscular disorders. Manual and semi-automated methods. Methods 2012;56(1):103-13
   PubMed Web of Science ®Google Scholar
• Calamini B, Silva MC, Madoux F, et al. Small-molecule proteostasis regulators for protein conformational diseases. Nat Chem Biol 2012;8(2):185-96
   Web of Science ®Google Scholar
• Hetz C, Chevet E, Harding HP. Targeting the unfolded protein response in disease. Nat Rev Drug Discov 2013;12(9):703-19
   PubMed Web of Science ®Google Scholar
• Ozcan U, Yilmaz E, Ozcan L, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006;313(5790):1137-40
   PubMed Web of Science ®Google Scholar
• Ryno LM, Wiseman RL, Kelly JW. Targeting unfolded protein response signaling pathways to ameliorate protein misfolding diseases. Curr Opin Chem Biol 2013;17(3):346-52
   PubMed Web of Science ®Google Scholar
• Westerheide SD, Morimoto RI. Heat shock response modulators as therapeutic tools for diseases of protein conformation. J Biol Chem 2005;280(39):33097-100
   PubMed Web of Science ®Google Scholar
• Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007;8(7):519-29
   PubMed Web of Science ®Google Scholar
• Morimoto RI. The heat shock response: systems biology of proteotoxic stress in aging and disease. Cold Spring Harb Symp Quant Biol 2011;76:91-9
   PubMedGoogle Scholar
• Morimoto RI. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 1998;12(24):3788-96
   PubMed Web of Science ®Google Scholar
• Voellmy R. Transduction of the stress signal and mechanisms of transcriptional regulation of heat shock/stress protein gene expression in higher eukaryotes. Crit Rev Eukaryot Gene Expr 1994;4(4):357-401
   PubMedGoogle Scholar
• Zhang Y, Huang L, Zhang J, et al. Targeted disruption of hsf1 leads to lack of thermotolerance and defines tissue-specific regulation for stress-inducible Hsp molecular chaperones. J Cell Biochem 2002;86(2):376-93
   PubMed Web of Science ®Google Scholar
• Lu L, Han AP, Chen JJ. Translation initiation control by heme-regulated eukaryotic initiation factor 2alpha kinase in erythroid cells under cytoplasmic stresses. Mol Cell Biol 2001;21(23):7971-80
   PubMed Web of Science ®Google Scholar
• Scheper GC, Thomas AA, van Wijk R. Inactivation of eukaryotic initiation factor 2B in vitro by heat shock. Biochem J 1998;334(Pt 2):463-7
   PubMedGoogle Scholar
• Gasch AP, Spellman PT, Kao CM, et al. Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 2000;11(12):4241-57
   PubMed Web of Science ®Google Scholar
• Heldens L, Hensen SM, Onnekink C, et al. An atypical unfolded protein response in heat shocked cells. PLoS One 2011;6(8):e23512
   Google Scholar
• Matsumoto R, Akama K, Rakwal R, Iwahashi H. The stress response against denatured proteins in the deletion of cytosolic chaperones SSA1/2 is different from heat-shock response in Saccharomyces cerevisiae. BMC Genomics 2005;6:141
   PubMedGoogle Scholar
• Kaneto H, Katakami N, Kawamori D, et al. Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 2007;9(3):355-66
   PubMed Web of Science ®Google Scholar
• Robertson R, Zhou H, Zhang T, Harmon JS. Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in type 2 diabetes. Cell Biochem Biophys 2007;48(2-3):139-46
   PubMed Web of Science ®Google Scholar
• Robertson RP. Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem 2004;279(41):42351-4
   PubMed Web of Science ®Google Scholar
• Cardozo AK, Ortis F, Storling J, et al. Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic beta-cells. Diabetes 2005;54(2):452-61
   PubMed Web of Science ®Google Scholar
• Chambers KT, Unverferth JA, Weber SM, et al. The role of nitric oxide and the unfolded protein response in cytokine-induced beta-cell death. Diabetes 2008;57(1):124-32
   PubMed Web of Science ®Google Scholar
• Kharroubi I, Ladriere L, Cardozo AK, et al. Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: role of nuclear factor-kappaB and endoplasmic reticulum stress. Endocrinology 2004;145(11):5087-96
   PubMed Web of Science ®Google Scholar
• Mujcic H, Rzymski T, Rouschop KM, et al. Hypoxic activation of the unfolded protein response (UPR) induces expression of the metastasis-associated gene LAMP3. Radiother Oncol 2009;92(3):450-9
   PubMed Web of Science ®Google Scholar
• Zheng X, Wang X, Ma Z, et al. Acute hypoxia induces apoptosis of pancreatic beta-cell by activation of the unfolded protein response and upregulation of CHOP. Cell Death Dis 2012;3:e322
   Google Scholar
• Hebert DN, Molinari M. In and out of the ER: protein folding, quality control, degradation, and related human diseases. Physiol Rev 2007;87(4):1377-408
   PubMed Web of Science ®Google Scholar
• Rodriguez M, Snoek LB, De Bono M, Kammenga JE. Worms under stress: C. elegans stress response and its relevance to complex human disease and aging. Trends Genet 2013;29(6):367-74
   PubMed Web of Science ®Google Scholar
• Travers KJ, Patil CK, Wodicka L, et al. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 2000;101(3):249-58
   PubMed Web of Science ®Google Scholar
• Ben-Zvi A, Miller EA, Morimoto RI. Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Proc Natl Acad Sci USA 2009;106(35):14914-19
   PubMed Web of Science ®Google Scholar
• David DC, Ollikainen N, Trinidad JC, et al. Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol 2010;8(8):e1000450
   PubMed Web of Science ®Google Scholar
• Morley JF, Brignull HR, Weyers JJ, Morimoto RI. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc Natl Acad Sci USA 2002;99(16):10417-22
   PubMed Web of Science ®Google Scholar
• Burkewitz K, Choe K, Strange K. Hypertonic stress induces rapid and widespread protein damage in C. elegans. Am J Physiol Cell Physiol 2011;301(3):C566-76
   Google Scholar
• Gidalevitz T, Ben-Zvi A, Ho KH, et al. Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 2006;311(5766):1471-4
   PubMed Web of Science ®Google Scholar
• Murphy CT. The search for DAF-16/FOXO transcriptional targets: approaches and discoveries. Exp Gerontol 2006;41(10):910-21
   PubMed Web of Science ®Google Scholar
• Murphy CT, McCarroll SA, Bargmann CI, et al. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 2003;424(6946):277-83
   PubMed Web of Science ®Google Scholar
• Park SK, Tedesco PM, Johnson TE. Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1. Aging Cell 2009;8(3):258-69
   PubMed Web of Science ®Google Scholar
• Chiang WC, Ching TT, Lee HC, et al. HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell 2012;148(1-2):322-34
   PubMed Web of Science ®Google Scholar
• Hsu AL, Murphy CT, Kenyon C. Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 2003;300(5622):1142-5
   PubMed Web of Science ®Google Scholar
• Melendez A, Talloczy Z, Seaman M, et al. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 2003;301(5638):1387-91
   PubMed Web of Science ®Google Scholar
• Hansen M, Chandra A, Mitic LL, et al. A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet 2008;4(2):e24
   PubMed Web of Science ®Google Scholar
• Huang H, Regan KM, Wang F, et al. Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc Natl Acad Sci USA 2005;102(5):1649-54
   PubMed Web of Science ®Google Scholar
• Vilchez D, Morantte I, Liu Z, et al. RPN-6 determines C. elegans longevity under proteotoxic stress conditions. Nature 2012;489(7415):263-8
   PubMed Web of Science ®Google Scholar
• Glover-Cutter KM, Lin S, Blackwell TK. Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. PLoS Genet 2013;9(9):e1003701
   Google Scholar
• Henis-Korenblit S, Zhang P, Hansen M, et al. Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci USA 2010;107(21):9730-5
   PubMed Web of Science ®Google Scholar
• Link CD. C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer’s disease. Exp Gerontol 2006;41(10):1007-13
   PubMed Web of Science ®Google Scholar
• Long OS, Benson JA, Kwak JH, et al. A C. elegans model of human alpha1-antitrypsin deficiency links components of the RNAi pathway to misfolded protein turnover. Hum Mol Genet 2014, doi:10.1093/hmg/ddu235
   Web of Science ®Google Scholar
• Giacomotto J, Segalat L. High-throughput screening and small animal models, where are we? Br J Pharmacol 2010;160(2):204-16
   PubMed Web of Science ®Google Scholar
• O’Reilly LP, Luke CJ, Perlmutter DH, et al. C. elegans in high-throughput drug discovery. Adv Drug Deliv Rev 2014;69-70C:247-53
   Web of Science ®Google Scholar
• Fatouros C, Pir GJ, Biernat J, et al. Inhibition of tau aggregation in a novel Caenorhabditis elegans model of tauopathy mitigates proteotoxicity. Hum Mol Genet 2012;21(16):3587-603
   PubMed Web of Science ®Google Scholar
• Gieseler K, Grisoni K, Segalat L. Genetic suppression of phenotypes arising from mutations in dystrophin-related genes in Caenorhabditis elegans. Curr Biol 2000;10(18):1092-7
   PubMed Web of Science ®Google Scholar
• Hamamichi S, Rivas RN, Knight AL, et al. Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson’s disease model. Proc Natl Acad Sci USA 2008;105(2):728-33
   PubMed Web of Science ®Google Scholar
• Li J, Li T, Zhang X, et al. Human superoxide dismutase 1 overexpression in motor neurons of Caenorhabditis elegans causes axon guidance defect and neurodegeneration. Neurobiol Aging 2014;35(4):837-46
   PubMed Web of Science ®Google Scholar
• McColl G, Roberts BR, Pukala TL, et al. Utility of an improved model of amyloid-beta (Abeta(1)(-)(4)(2)) toxicity in Caenorhabditis elegans for drug screening for Alzheimer’s disease. Mol Neurodegener 2012;7:57
   PubMed Web of Science ®Google Scholar
• Siddiqui SS, Loganathan S, Krishnaswamy S, et al. C. elegans as a model organism for in vivo screening in cancer: effects of human c-Met in lung cancer affect C. elegans vulva phenotypes. Cancer Biol Ther 2008;7(6):856-63
   PubMed Web of Science ®Google Scholar
• Wang J, Farr GW, Hall DH, et al. An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans. PLoS Genet 2009;5(1):e1000350
   PubMed Web of Science ®Google Scholar
• Caruso ME, Jenna S, Bouchecareilh M, et al. GTPase-mediated regulation of the unfolded protein response in Caenorhabditis elegans is dependent on the AAA+ ATPase CDC-48. Mol Cell Biol 2008;28(13):4261-74
   PubMed Web of Science ®Google Scholar
• Leung CK, Wang Y, Malany S, et al. An ultra high-throughput, whole-animal screen for small molecule modulators of a specific genetic pathway in Caenorhabditis elegans. PLoS One 2013;8(4):e62166
   PubMed Web of Science ®Google Scholar
• Li J, Pak SC, O’Reilly LP, et al. Fluphenazine Reduces Proteotoxicity in C. elegans and Mammalian Models of Alpha-1-Antitrypsin Deficiency. PLoS One 2014;9(1):e87260
   Google Scholar
• Miedel MT, Graf NJ, Stephen KE, et al. A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-associated degradation in C. elegans. PLoS One 2012;7(7):e40145
   PubMed Web of Science ®Google Scholar
• Morley JF, Morimoto RI. Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 2004;15(2):657-64
   PubMed Web of Science ®Google Scholar
• Segref A, Torres S, Hoppe T. A screenable in vivo assay to study proteostasis networks in Caenorhabditis elegans. Genetics 2011;187(4):1235-40
   PubMed Web of Science ®Google Scholar
• Kwok TC, Ricker N, Fraser R, et al. A small-molecule screen in C. elegans yields a new calcium channel antagonist. Nature 2006;441(7089):91-5
   PubMed Web of Science ®Google Scholar
• Kaletta T, Hengartner MO. Finding function in novel targets: C. elegans as a model organism. Nat Rev Drug Discov 2006;5(5):387-98
   PubMed Web of Science ®Google Scholar
• Saur T, DeMarco SE, Ortiz A, et al. A genome-wide RNAi screen in Caenorhabditis elegans identifies the nicotinic acetylcholine receptor subunit ACR-7 as an antipsychotic drug target. PLoS Genet 2013;9(2):e1003313
   Google Scholar
• O’Reilly LP, Long OS, Cobanoglu MC, et al. A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of alpha1-antitrypsin deficiency. Hum Mol Genet 2014, doi:10.1093/hmg/ddu236
   Web of Science ®Google Scholar
• Breger J, Fuchs BB, Aperis G, et al. Antifungal chemical compounds identified using a C. elegans pathogenicity assay. PLoS Pathog 2007;3(2):e18
   PubMed Web of Science ®Google Scholar
• Lindblom TH, Dodd AK. Xenobiotic detoxification in the nematode Caenorhabditis elegans. J Exp Zool A Comp Exp Biol 2006;305(9):720-30
   PubMedGoogle Scholar
• Burns AR, Wallace IM, Wildenhain J, et al. A predictive model for drug bioaccumulation and bioactivity in Caenorhabditis elegans. Nat Chem Biol 2010;6(7):549-57
   PubMed Web of Science ®Google Scholar
• Collins JJ, Evason K, Kornfeld K. Pharmacology of delayed aging and extended lifespan of Caenorhabditis elegans. Exp Gerontol 2006;41(10):1032-9
   PubMed Web of Science ®Google Scholar
• Davies AG, Pierce-Shimomura JT, Kim H, et al. A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans. Cell 2003;115(6):655-66
   PubMed Web of Science ®Google Scholar
• Evason K, Huang C, Yamben I, et al. Anticonvulsant medications extend worm life-span. Science 2005;307(5707):258-62
   PubMed Web of Science ®Google Scholar
• Zheng SQ, Ding AJ, Li GP, et al. Drug absorption efficiency in Caenorhbditis elegans delivered by different methods. PLoS One 2013;8(2):e56877
   Google Scholar
• Partridge FA, Tearle AW, Gravato-Nobre MJ, et al. The C. elegans glycosyltransferase BUS-8 has two distinct and essential roles in epidermal morphogenesis. Dev Biol 2008;317(2):549-59
   PubMed Web of Science ®Google Scholar
• Arya U, Das CK, Subramaniam JR. Caenorhabditis elegans for preclinical drug discovery. Current Science 2010;99(12):1669-80
   Web of Science ®Google Scholar
• Fribley AM, Cruz PG, Miller JR, et al. Complementary cell-based high-throughput screens identify novel modulators of the unfolded protein response. J Biomol Screen 2011;16(8):825-35
   PubMed Web of Science ®Google Scholar
• Rowlands MG, Newbatt YM, Prodromou C, et al. High-throughput screening assay for inhibitors of heat-shock protein 90 ATPase activity. Anal Biochem 2004;327(2):176-83
   PubMed Web of Science ®Google Scholar
• Xu S, Butkevich AN, Yamada R, et al. Discovery of an orally active small-molecule irreversible inhibitor of protein disulfide isomerase for ovarian cancer treatment. Proc Natl Acad Sci USA 2012;109(40):16348-53
   PubMed Web of Science ®Google Scholar
• Lawson B, Brewer JW, Hendershot LM. Geldanamycin, an hsp90/GRP94-binding drug, induces increased transcription of endoplasmic reticulum (ER) chaperones via the ER stress pathway. J Cell Physiol 1998;174(2):170-8
   PubMed Web of Science ®Google Scholar
• Solit DB, Osman I, Polsky D, et al. Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma. Clin Cancer Res 2008;14(24):8302-7
   PubMed Web of Science ®Google Scholar
• Powers MV, Workman P. Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors. Endocr Relat Cancer 2006;13(Suppl 1):S125-35
   Google Scholar
• Nagai Y, Fujikake N, Popiel HA, Wada K. Induction of molecular chaperones as a therapeutic strategy for the polyglutamine diseases. Curr Pharm Biotechnol 2010;11(2):188-97
   PubMed Web of Science ®Google Scholar
• Volkmann K, Lucas JL, Vuga D, et al. Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease. J Biol Chem 2011;286(14):12743-55
   PubMed Web of Science ®Google Scholar
• Cross BC, Bond PJ, Sadowski PG, et al. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc Natl Acad Sci USA 2012;109(15):E869-78
   PubMed Web of Science ®Google Scholar
• Papandreou I, Denko NC, Olson M, et al. Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood 2011;117(4):1311-14
   PubMed Web of Science ®Google Scholar
• Tomasio SM, Harding HP, Ron D, et al. Selective inhibition of the unfolded protein response: targeting catalytic sites for Schiff base modification. Mol Biosyst 2013;9(10):2408-16
   PubMed Web of Science ®Google Scholar
• Zhang YQ, Sarge KD. Celastrol inhibits polyglutamine aggregation and toxicity though induction of the heat shock response. J Mol Med 2007;85(12):1421-8
   PubMed Web of Science ®Google Scholar
• Kiaei M, Kipiani K, Petri S, et al. Celastrol blocks neuronal cell death and extends life in transgenic mouse model of amyotrophic lateral sclerosis. Neurodegener Dis 2005;2(5):246-54
   PubMed Web of Science ®Google Scholar
• Yang C, Rahimpour S, Lu J, et al. Histone deacetylase inhibitors increase glucocerebrosidase activity in Gaucher disease by modulation of molecular chaperones. Proc Natl Acad Sci USA 2013;110(3):966-71
   PubMed Web of Science ®Google Scholar
• Bouchecareilh M, Hutt DM, Szajner P, et al. Histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA)-mediated correction of alpha1-antitrypsin deficiency. J Biol Chem 2012;287(45):38265-78
   PubMedGoogle Scholar
• Di XJ, Han DY, Wang YJ, et al. SAHA enhances Proteostasis of epilepsy-associated α1(A322D)beta2gamma2 GABA(A) receptors. Chem Biol 2013;20(12):1456-68
   PubMed Web of Science ®Google Scholar
• Chen W, Wang S, Tian T, et al. Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies. Eur J Hum Genet 2009;17(12):1668-75
   PubMed Web of Science ®Google Scholar
• Mitsiades CS, Mitsiades NS, McMullan CJ, et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell 2004;5(3):221-30
   PubMed Web of Science ®Google Scholar
• Reuveni H, Flashner-Abramson E, Steiner L, et al. Therapeutic destruction of insulin receptor substrates for cancer treatment. Cancer Res 2013;73(14):4383-94
   PubMed Web of Science ®Google Scholar
• El-Ami T, Moll L, Carvalhal Marques F, et al. A novel inhibitor of the insulin/IGF signaling pathway protects from age-onset, neurodegeneration-linked proteotoxicity. Aging Cell 2014;13(1):165-74
   PubMed Web of Science ®Google Scholar
• Neef DW, Turski ML, Thiele DJ. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease. PLoS Biol 2010;8(1):e1000291
   Google Scholar
• Bouck DC, Shu P, Cui J, et al. A high-content screen identifies inhibitors of nuclear export of forkhead transcription factors. J Biomol Screen 2011;16(4):394-404
   PubMed Web of Science ®Google Scholar
• Link W, Oyarzabal J, Serelde BG, et al. Chemical interrogation of FOXO3a nuclear translocation identifies potent and selective inhibitors of phosphoinositide 3-kinases. J Biol Chem 2009;284(41):28392-400
   PubMed Web of Science ®Google Scholar
• Wu KC, McDonald PR, Liu JJ, et al. Implementation of a high-throughput screen for identifying small molecules to activate the Keap1-Nrf2-ARE pathway. PLoS One 2012;7(10):e44686
   Google Scholar
• Petrascheck M, Ye X, Buck LB. A high-throughput screen for chemicals that increase the lifespan of Caenorhabditis elegans. Ann NY Acad Sci 2009;1170:698-701
   PubMed Web of Science ®Google Scholar
• Garcia SM, Casanueva MO, Silva MC, et al. Neuronal signaling modulates protein homeostasis in Caenorhabditis elegans post-synaptic muscle cells. Genes Dev 2007;21(22):3006-16
   PubMed Web of Science ®Google Scholar
• Keowkase R, Aboukhatwa M, Luo Y. Fluoxetine protects against amyloid-beta toxicity, in part via daf-16 mediated cell signaling pathway, in Caenorhabditis elegans. Neuropharmacology 2010;59(4-5):358-65
   PubMed Web of Science ®Google Scholar
• Townsend M, Mehta T, Selkoe DJ. Soluble Abeta inhibits specific signal transduction cascades common to the insulin receptor pathway. J Biol Chem 2007;282(46):33305-12
   PubMed Web of Science ®Google Scholar
• Zhao WQ, De Felice FG, Fernandez S, et al. abeta oligomers induce impairment of neuronal insulin receptors. FASEB J 2008;22(1):246-60
   PubMed Web of Science ®Google Scholar
• Zhao WQ, Lacor PN, Chen H, et al. Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric abeta. J Biol Chem 2009;284(28):18742-53
   PubMed Web of Science ®Google Scholar