Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice

Brain

Volumn 140, Issue 6, 2017, Pages 1768-1783

  Halliday, Mark ^a   Radford, Helois ^a   Zents, Karlijn A M ^b   Molloy, Collin ^a   Moreno, Julie A ^a   Verity, Nicholas C ^a   Smith, Ewan ^a   Ortori, Catharine A ^c   Barrett, David A ^c   Bushell, Martin ^a   Mallucci, Giovanna R ^a,b  

^a MRC TOXICOLOGY UNIT   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

Dementia; Drug repurposing; Neurodegeneration; Therapeutics

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; DIBENZOYLMETHANE DERIVATIVE; FIREFLY LUCIFERASE; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; INITIATION FACTOR 2ALPHA; MESSENGER RNA; PUROMYCIN; RENILLA LUCIFERIN 2 MONOOXYGENASE; TRAZODONE; TUNICAMYCIN; X BOX BINDING PROTEIN 1; CHALCONE DERIVATIVE; DIBENZOYLMETHANE; NEUROPROTECTIVE AGENT; PERK KINASE; PROTEIN KINASE INHIBITOR; PROTEIN KINASE R;

5' UNTRANSLATED REGION; ALZHEIMER DISEASE; AMNESIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD BRAIN BARRIER; CELL CULTURE; CHO CELL LINE; CONTROLLED STUDY; ENDOPLASMIC RETICULUM STRESS; ENZYME REPRESSION; EX VIVO STUDY; FEMALE; FRONTOTEMPORAL DEMENTIA; HEK293 CELL LINE; HISTOLOGY; HUMAN; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; INTRACELLULAR SIGNALING; LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY; LUCIFERASE ASSAY; MEMORY DISORDER; MEMORY TEST; MOLECULAR LIBRARY; MOUSE; NERVE DEGENERATION; NEUROLOGIC DISEASE; NEUROPROTECTION; NONHUMAN; OPEN READING FRAME; POLYMERASE CHAIN REACTION; PRION DISEASE; PRIORITY JOURNAL; PROTEIN SYNTHESIS; PROTEIN TARGETING; SITE DIRECTED MUTAGENESIS; TAUOPATHY; UNFOLDED PROTEIN RESPONSE; ANIMAL; ANIMAL BEHAVIOR; ANTAGONISTS AND INHIBITORS; COMPLICATION; DISEASE MODEL; MEMORY DISORDERS; PRION DISEASES; SIGNAL TRANSDUCTION;

ANIMALS; BEHAVIOR, ANIMAL; CHALCONES; DISEASE MODELS, ANIMAL; EIF-2 KINASE; FRONTOTEMPORAL DEMENTIA; MEMORY DISORDERS; MICE; NEUROPROTECTIVE AGENTS; PRION DISEASES; PROTEIN KINASE INHIBITORS; SIGNAL TRANSDUCTION; TRAZODONE; UNFOLDED PROTEIN RESPONSE;

EID: 85020602496     PISSN: 00068950     EISSN: 14602156     Source Type: Journal    
DOI: 10.1093/brain/awx074     Document Type: Article

References (49)

1. Celardo I, Costa AC, Lehmann S, Jones C, Wood N, Mencacci NE, et al. Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson's disease. Cell Death Dis 2016; 7: e2271.
2. Devi L, Ohno M. PERK mediates eIF2 alpha phosphorylation responsible for BACE1 elevation, CREB dysfunction and neurodegeneration in a mouse model of Alzheimer's disease. Neurobiol Aging 2014; 35: 2272-81.
3. Dinkova-Kostova AT, Talalay P. Relation of structure of curcumin analogs to their potencies as inducers of Phase 2 detoxification enzymes. Carcinogenesis 1999; 20: 911-14.
4. Frazier MC, Jackson KM, Jankowska-Stephens E, Anderson MG, Harris WB. Proteomic analysis of proteins altered by dibenzoylmethane in human prostatic cancer LNCaP cells. Proteomics 2004; 4: 2814-21.
5. Halliday M, Mallucci GR. Modulating the unfolded protein response to prevent neurodegeneration and enhance memory. Neuropathol Appl Neurobiol 2015; 41: 414-27.
6. Halliday M, Radford H, Sekine Y, Moreno J, Verity N, le Quesne J, et al. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death Dis 2015; 6: e1672.
7. Harding HP, Zhang Y, Khersonsky S, Marciniak S, Scheuner D, Kaufman RJ, et al. Bioactive small molecules reveal antagonism between the integrated stress response and sterol-regulated gene expression. Cell Metab 2005; 2: 361-71.
8. He CH, Gong P, Hu B, Stewart D, Choi ME, Choi AM, et al. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J Biol Chem 2001; 276: 20858-65.
9. Hegedus C, Lakatos P, Kiss-Szikszai A, Patonay T, Gergely S, Gregus A, et al. Cytoprotective dibenzoylmethane derivatives protect cells from oxidative stress-induced necrotic cell death. Pharmacol Res 2013; 72: 25-34.
10. Hetz C, Chevet E, Harding HP. Targeting the unfolded protein response in disease. Nat Rev Drug Discov 2013; 12: 703-19.
11. Hoozemans JJ, van Haastert ES, Eikelenboom P, de Vos RA, Rozemuller JM, Scheper W. Activation of the unfolded protein response in Parkinson's disease. Biochem Biophys Res Commun 2007; 354: 707-11.
12. Hoozemans JJ, van Haastert ES, Nijholt DA, Rozemuller AJ, Eikelenboom P, Scheper W. The unfolded protein response is activated in pretangle neurons in Alzheimer's disease hippocampus. Am J Pathol 2009; 174: 1241-51.
13. Huang MT, Lou YR, Xie JG, Ma W, Lu YP, Yen P, et al. Effect of dietary curcumin and dibenzoylmethane on formation of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and lymphomas/ leukemias in Sencar mice. Carcinogenesis 1998; 19: 1697-700.
14. Khor TO, Yu S, Barve A, Hao X, Hong JL, Lin W, et al. Dietary feeding of dibenzoylmethane inhibits prostate cancer in transgenic adenocarcinoma of the mouse prostate model. Cancer Res 2009; 69: 7096-102.
15. Kim HJ, Raphael AR, LaDow ES, McGurk L, Weber RA, Trojanowski JQ, et al. Therapeutic modulation of eIF2alpha phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nature Genet 2014; 46: 152-60.
16. Kumar P, Kalonia H, Kumar A. Nitric oxide mechanism in the protective effect of antidepressants against 3-nitropropionic acidinduced cognitive deficit, glutathione and mitochondrial alterations in animal model of Huntington's disease. Behav Pharmacol 2010; 21: 217-30.
17. Kumar P, Kalonia H, Kumar A. Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington's-like symptoms: a comparative study. J Psychopharmacol 2011; 25: 1399-411.
18. Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord 2004; 17: 355-9.
19. Lopez-Pousa S, Garre-Olmo J, Vilalta-Franch J, Turon-Estrada A, Pericot-Nierga I. Trazodone for Alzheimer's disease: a naturalistic follow-up study. Arch Gerontol Geriatr 2008; 47: 207-15.
20. Ma T, Trinh MA, Wexler AJ, Bourbon C, Gatti E, Pierre P, et al. Suppression of eIF2alpha kinases alleviates Alzheimer's diseaserelated plasticity and memory deficits. Nat Neurosci 2013; 16: 1299-305.
21. Mallucci G, Dickinson A, Linehan J, Klohn PC, Brandner S, Collinge J. Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 2003; 302: 871-4.
22. Mallucci GR, Ratte S, Asante EA, Linehan J, Gowland I, Jefferys JG, et al. Post-natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration. EMBO J 2002; 21: 202-10.
23. McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in Alzheimer's disease. Cochrane Database Syst Rev 2014; 3: CD009178.
24. Meijer HA, Kong YW, Lu WT, Wilczynska A, Spriggs RV, Robinson SW, et al. Translational repression and eIF4A2 activity are critical for microRNA-mediated gene regulation. Science 2013; 340: 82-5.
25. Monti JM, Pellejero T, Jantos H. Effects of H1-and H2-histamine receptor agonists and antagonists on sleep and wakefulness in the rat. J Neural Transm 1986; 66: 1-11.
26. Moreno JA, Halliday M, Molloy C, Radford H, Verity N, Axten JM, et al. Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice. Sci Transl Med 2013; 5: 206ra138.
27. Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Martin MG, et al. Sustained translational repression by eIF2alpha-P mediates prion neurodegeneration. Nature 2012; 485: 507-11.
28. Nijholt DA, Nolle A, van Haastert ES, Edelijn H, Toonen RF, Hoozemans JJ, et al. Unfolded protein response activates glycogen synthase kinase-3 via selective lysosomal degradation. Neurobiol Aging 2013; 34: 1759-71.
29. Nijholt DA, van Haastert ES, Rozemuller AJ, Scheper W, Hoozemans JJ. The unfolded protein response is associated with early tau pathology in the hippocampus of tauopathies. J Pathol 2012; 226: 693-702.
30. Oslowski CM, Urano F. Measuring ER stress and the unfolded protein response using mammalian tissue culture system. Methods Enzymol 2011; 490: 71-92.
31. Peretti D, Bastide A, Radford H, Verity N, Molloy C, Martin MG, et al. RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration. Nature 2015; 518: 236-9.
32. Quaglio E, Restelli E, Garofoli A, Dossena S, De Luigi A, Tagliavacca L, et al. Expression of mutant or cytosolic PrP in transgenic mice and cells is not associated with endoplasmic reticulum stress or proteasome dysfunction. PLoS One 2011; 6: e19339.
33. Radford H, Moreno JA, Verity N, Halliday M, Mallucci GR. PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia. Acta Neuropathol 2015; 130: 633-42.
34. Ramsden M, Kotilinek L, Forster C, Paulson J, McGowan E, SantaCruz K, et al. Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L). J Neurosci 2005; 25: 10637-47.
35. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008; 22: 659-61.
36. Richardson CE, Kinkel S, Kim DH. Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity. PLoS Genet 2011; 7: e1002391.
37. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007; 8: 519-29.
38. Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005; 309: 476-81.
39. Sekine Y, Zyryanova A, Crespillo-Casado A, Fischer PM, Harding HP, Ron D. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science 2015; 348: 1027-30.
40. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. eLife 2013; 2: e00498.
41. Sidrauski C, Tsai JC, Kampmann M, Hearn BR, Vedantham P, Jaishankar P, et al. Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response. eLife 2015; 4: e07314.
42. Smith HL, Mallucci GR. The unfolded protein response: mechanisms and therapy of neurodegeneration. Brain 2016; 139 (Pt 8): 2113-21.
43. Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 2009; 136: 731-45.
44. Stahl SM. Mechanism of action of trazodone: a multifunctional drug. CNS Spectr 2009; 14: 536-46.
45. Stutzbach LD, Xie SX, Naj AC, Albin R, Gilman S, Group PSPGS, et al. The unfolded protein response is activated in disease-affected brain regions in progressive supranuclear palsy and Alzheimer's disease. Acta Neuropathol Commun 2013; 1: 31.
46. Takano K, Kitao Y, Tabata Y, Miura H, Sato K, Takuma K, et al. A dibenzoylmethane derivative protects dopaminergic neurons against both oxidative stress and endoplasmic reticulum stress. Am J Physiol Cell Physiol 2007; 293: C1884-94.
47. Thimmulappa RK, Rangasamy T, Alam J, Biswal S. Dibenzoylmethane activates Nrf2-dependent detoxification pathway and inhibits benzo(a)pyrene induced DNA adducts in lungs. Med Chem 2008; 4: 473-81.
48. van der Harg JM, Nolle A, Zwart R, Boerema AS, van Haastert ES, Strijkstra AM, et al. The unfolded protein response mediates reversible tau phosphorylation induced by metabolic stress. Cell Death Dis 2014; 5: e1393.
49. Vattem KM, Wek RC. Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proc Natl Acad Sci U S A 2004; 101: 11269-74.