Methylene blue modulates Huntingtin aggregation intermediates and is protective in Huntington's disease models

Journal of Neuroscience

Volumn 32, Issue 32, 2012, Pages 11109-11119

  Sontag, Emily Mitchell ^a   Lotz, Gregor P ^b,c   Agrawal, Namita ^a,e   Tran, Andrew ^a   Aron, Rebecca ^b,c   Yang, Guocheng ^b,c   Necula, Mihaela ^a   Lau, Alice ^a   Finkbeiner, Steven ^b,c,d   Glabe, Charles ^a   Marsh, J Lawrence ^a   Muchowski, Paul J ^b,c,d   Thompson, Leslie M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b GLADSTONE INSTITUTE OF NEUROLOGICAL DISEASE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e UNIVERSITY OF DELHI   (India)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; HUNTINGTIN; METHYLENE BLUE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATOMIC FORCE MICROSCOPY; CONTROLLED STUDY; DROSOPHILA MELANOGASTER; EMBRYO; HUNTINGTON CHOREA; IMMUNOHISTOCHEMISTRY; MOUSE; NERVE DEGENERATION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; ROTAROD TEST;

ANALYSIS OF VARIANCE; ANIMALS; BRAIN-DERIVED NEUROTROPHIC FACTOR; CELLS, CULTURED; CEREBRAL CORTEX; DISEASE MODELS, ANIMAL; DROSOPHILA; EMBRYO, MAMMALIAN; ENZYME INHIBITORS; EXCITATORY AMINO ACID ANTAGONISTS; HUMANS; HUNTINGTON DISEASE; KYNURENIC ACID; METHYLENE BLUE; MICE; MICE, INBRED C57BL; MICROSCOPY, ATOMIC FORCE; MUTATION; NERVE TISSUE PROTEINS; NEURODEGENERATIVE DISEASES; NEURONS; PSYCHOMOTOR PERFORMANCE; RATS; ROTAROD PERFORMANCE TEST; TRANSFECTION; TRINUCLEOTIDE REPEAT EXPANSION;

EID: 84864862868     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.0895-12.2012     Document Type: Article

References (61)

1. Apostol BL, Simmons DA, Zuccato C, Illes K, Pallos J, Casale M, Conforti P, Ramos C, Roarke M, Kathuria S, Cattaneo E, Marsh JL, Thompson LM (2008) CEP-1347 reduces mutant huntingtin-associated neurotoxicity and restores BDNF levels in R6/2 mice. Mol Cell Neurosci 39:8-20.
2. Arrasate M, Finkbeiner S (2005) Automated microscope system for determining factors that predict neuronal fate. Proc Natl Acad Sci U S A 102:3840-3845.
3. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S (2004) Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431:805-810.
4. Atamna H, Kumar R (2010) Protective role of methylene blue in Alzheimer's disease via mitochondria and cytochrome c oxidase. J Alzheimers Disease 20 [Suppl 2]:S439-S452.
5. Atamna H, Krugliak M, Shalmiev G, Deharo E, Pescarmona G, Ginsburg H (1996) Mode of antimalarial effect of methylene blue and some of its analogues on Plasmodium falciparum in culture and their inhibition of P. vinckei petteri and P. yoelii nigeriensis in vivo. Biochemical Pharmacol 51:693-700.
6. Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN (2008) Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. FASEB J 22:703-712.
7. Behrends C, Langer CA, Boteva R, Bottcher UM, Stemp MJ, Schaffar G, Rao BV, Giese A, Kretzschmar H, Siegers K, Hartl FU (2006) Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic oligomers. Mol Cell 23:887-897.
8. Callaway NL, Riha PD, Bruchey AK, Munshi Z, Gonzalez-Lima F (2004) Methylene blue improves brain oxidative metabolism and memory retention in rats. Pharmacol Biochemistry Behav 77:175-181.
9. Carter RJ, Lione LA, Humby T, Mangiarini L, Mahal A, Bates GP, Dunnett SB, Morton AJ (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. J Neurosci 19:3248-3257.
10. Chopra V, Fox JH, Lieberman G, Dorsey K, Matson W, Waldmeier P, Housman DE, Kazantsev A, Young AB, Hersch S (2007) A small-molecule therapeutic lead for Huntington's disease: preclinical pharmacology and efficacy of C2-8 in the R6/2 transgenic mouse. Proc Natl Acad Sci U S A 104:16685-16689.
11. Conforti P, Ramos C, Apostol BL, Simmons DA, Nguyen HP, Riess O, Thompson LM, Zuccato C, Cattaneo E (2008) Blood level of brainderived neurotrophic factor mRNA is progressively reduced in rodent models of Huntington's disease: restoration by the neuroprotective compound CEP-1347. Mol Cell Neurosci 39:1-7.
12. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90:537-548.
13. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277:1990-1993.
14. DiSanto AR, Wagner JG (1972) Pharmacokinetics of highly ionized drugs. II. Methylene blue-absorption, metabolism, and excretion in man and dog after oral administration. J Pharm Sci 61:1086-1090.
15. Doh-Ura K, Iwaki T, Caughey B (2000) Lysosomotropic agents and cysteine protease inhibitors inhibit scrapie-associated prion protein accumulation. J Virol 74:4894-4897.
16. Donovan J, Brown P (2006) Euthanasia. Curr Protoc Immunol. 73:1.8.1-1.8.4.
17. Ehrlich P, Guttman P (1891) Ueber die wirkung des methylenblau bei malaria. Berlin Klin Wochenschr 28:953-956.
18. Faber P, Ronald A, Millar BW (2005) Methylthioninium chloride: pharmacology and clinical applications with special emphasis on nitric oxide mediated vasodilatory shock during cardiopulmonary bypass. Anaesthesia 60:575-587.
19. Gauthier LR, Charrin BC, Borrell-Pagés M, Dompierre JP, Rangone H, Cordeliéres FP, De Mey J, MacDonald ME, Lessmann V, Humbert S, Saudou F (2004) Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 118:127-138.
20. The Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72:971-983.
21. Gura T (2008) Hope in Alzheimer's fight emerges from unexpected places. Nat Med 14:894.
22. Gusella JF, MacDonald ME (1995) Huntington's disease. Semin Cell Biol 6:21-28.
23. Harper PS (1991) Huntington's disease. London: W.B. Saunders.
24. Hickey MA, Kosmalska A, Enayati J, Cohen R, Zeitlin S, Levine MS, Chesselet MF (2008) Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in knock-in Huntington's disease mice. Neuroscience 157:280-295.
25. Korth C, May BC, Cohen FE, Prusiner SB (2001) Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc Natl Acad Sci U S A 98:9836-9841.
26. Kristiansen JE (1989) Dyes, antipsychotic drugs, and antimicrobial activity. Fragments of a development, with special reference to the influence of Paul Ehrlich. Danish Med Bull 36:178-185.
27. Küpfer A, Aeschlimann C, Wermuth B, Cerny T (1994) Prophylaxis and reversal of ifosfamide encephalopathy with methylene-blue. Lancet 343:763-764.
28. Kwok ES, Howes D (2006) Use of methylene blue in sepsis: a systematic review. J Intensive Care Med 21:359-363.
29. Legleiter J, Mitchell E, Lotz GP, Sapp E, Ng C, DiFiglia M, Thompson LM, Muchowski PJ (2010) Mutant huntingtin fragments form oligomers in a polyglutamine length-dependent manner in vitro and in vivo. J Biol Chem 285:14777-14790.
30. Lotz GP, Legleiter J, Aron R, Mitchell EJ, Huang SY, Ng C, Glabe C, Thompson LM, Muchowski PJ (2010) Hsp70 and Hsp40 functionally interact with soluble mutant huntingtin oligomers in a classic ATP-dependent reaction cycle. J Biol Chem 285:38183-38193.
31. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW, Bates GP (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493-506.
32. Mansouri A, Lurie AA (1993) Concise review: methemoglobinemia. Am J Hematol 42:7-12.
33. Medina DX, Caccamo A, Oddo S (2010) Methylene blue reduces aβ levels and rescues early cognitive deficit by increasing proteasome activity. Brain Pathol 21:140-149.
34. Miller J, Arrasate M, Brooks E, Libeu CP, Legleiter J, Hatters D, Curtis J, Cheung K, Krishnan P, Mitra S, Widjaja K, Shaby BA, Lotz GP, Newhouse Y, Mitchell EJ, Osmand A, Gray M, Thulasiramin V, Saudou F, Segal M, et al. (2011) Identifying polyglutamine protein species in situ that best predict neurodegeneration. Nat Chem Biol 7:925-934.
35. Moreno-Villoslada I, Torres-Gallegos C, Araya-Hermosilla R, Nishide H (2010) Influence of the linear aromatic density on methylene blue aggregation around polyanions containing sulfonate groups. J Phys Chem B 114:4151-4158.
36. Muchowski PJ, Schaffar G, Sittler A, Wanker EE, Hayer-Hartl MK, Hartl FU (2000) Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc Natl Acad Sci U S A 97:7841-7846.
37. Naylor GJ, Martin B, Hopwood SE, Watson Y (1986) A two-year doubleblind crossover trial of the prophylactic effect of methylene blue in manicdepressive psychosis. Biol Psychiatry 21:915-920.
38. Necula M, Breydo L, Milton S, Kayed R, van der Veer WE, Tone P, Glabe CG (2007) Methylene blue inhibits amyloid Aβ oligomerization by promoting fibrillization. Biochemistry 46:8850-8860.
39. O'Leary JC 3rd, Li Q, Marinec P, Blair LJ, Congdon EE, Johnson AG, Jinwal UK, Koren J 3rd, Jones JR, Kraft C, Peters M, Abisambra JF, Duff KE, Weeber EJ, Gestwicki JE, Dickey CA (2010) Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener 5:45.
40. Patel PN (2006) Methylene blue for management of Ifosfamide-induced encephalopathy. Ann Pharmacother 40:299-303.
41. Pelgrims J, De Vos F, Van den Brande J, Schrijvers D, Prové A, Vermorken JB (2000) Methylene blue in the treatment and prevention of ifosfamideinduced encephalopathy: report of 12 cases and a review of the literature. Br J Cancer 82:291-294.
42. Peng Q, Masuda N, Jiang M, Li Q, Zhao M, Ross CA, Duan W (2008) The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington's disease mouse model. Exp Neurol 210:154-163.
43. Peter C, Hongwan D, Küpfer A, Lauterburg BH (2000) Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol 56:247-250.
44. Riha PD, Bruchey AK, Echevarria DJ, Gonzalez-Lima F (2005) Memory facilitation by methylene blue: dose-dependent effect on behavior and brain oxygen consumption. Eur J Pharmacol 511:151-158.
45. Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lehrach H, Wanker EE (1997) Huntingtinencoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 90:549-558.
46. Sontag EM, Lotz GP, Yang G, Sontag CJ, Cummings BJ, Glabe CG, Muchowski PJ, Thompson LM (2012) Detection of mutant Huntingtin aggregation conformers and modulation of SDS-soluble fibrillar oligomers by small molecules. J Hunting Dis 1:119-132.
47. Southwell AL, Ko J, Patterson PH (2009) Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington's disease. J Neurosci 29:13589-13602.
48. Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, Apostol BL, Kazantsev A, Schmidt E, Zhu YZ, Greenwald M, Kurokawa R, Housman DE, Jackson GR, Marsh JL, Thompson LM (2001) Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413:739-743.
49. Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, Kurosawa M, Nekooki M, Nukina N (2004) Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med 10:148-154.
50. Taniguchi S, Suzuki N, Masuda M, Hisanaga S, Iwatsubo T, Goedert M, Hasegawa M (2005) Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins. J Biol Chem 280:7614-7623.
51. van Bebber F, Paquet D, Hruscha A, Schmid B, Haass C (2010) Methylene blue fails to inhibit Tau and polyglutamine protein dependent toxicity in zebrafish. Neurobiol Dis 39:265-271.
52. Wacker JL, Zareie MH, Fong H, Sarikaya M, Muchowski PJ (2004) Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nat Struct Mol Biol 11:1215-1222.
53. Walter-Sack I, Rengelshausen J, Oberwittler H, Burhenne J, Mueller O, Meissner P, Mikus G (2009) High absolute bioavailability of methylene blue given as an aqueous oral formulation. Eur J Clin Pharmacol 65:179-189.
54. Wang AM, Morishima Y, Clapp KM, Peng HM, Pratt WB, Gestwicki JE, Osawa Y, Lieberman AP (2010) Inhibition of hsp70 by methylene blue affects signaling protein function and ubiquitination and modulates polyglutamine protein degradation. J Biol Chem 285:15714-15723.
55. Wanker EE, Scherzinger E, Heiser V, Sittler A, Eickhoff H, Lehrach H (1999) Membrane filter assay for detection of amyloid-like polyglutaminecontaining protein aggregates. Methods Enzymol 309:375-386.
56. Weiss A, Klein C, Woodman B, Sathasivam K, Bibel M, Régulier E, Bates GP, Paganetti P (2008) Sensitive biochemical aggregate detection reveals aggregation onset before symptom development in cellular and murine models of Huntington's disease. J Neurochem 104:846-858.
57. Wischik CM, Edwards PC, Lai RY, Roth M, Harrington CR (1996) Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci U S A 93:11213-11218.
58. Wrubel KM, Riha PD, Maldonado MA, McCollum D, Gonzalez-Lima F (2007) The brain metabolic enhancer methylene blue improves discrimination learning in rats. Pharmacol Biochem Behav 86:712-717.
59. Yero T, Rey JA (2008) Tetrabenazine (Xenazine), an FDA-approved treatment option for Huntington's disease-related chorea. P T 33:690-694.
60. Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, Timmusk T, Sipione S, Cattaneo E (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 293:493-498.
61. Zuccato C, Liber D, Ramos C, Tarditi A, Rigamonti D, Tartari M, Valenza M, Cattaneo E (2005) Progressive loss of BDNF in a mouse model of Huntington's disease and rescue by BDNF delivery. Pharmacol Res 52:133-139.