PBT2 reduces toxicity in a C. elegans model of polyQ aggregation and extends lifespan, reduces striatal atrophy and improves motor performance in the R6/2 mouse model of Huntington's disease

Journal of Huntington's Disease

Volumn 1, Issue 2, 2012, Pages 211-219

  Cherny, Robert A ^a,b   Ayton, Scott ^a   Finkelstein, David I ^a,b   Bush, Ashley I ^a   McColl, Gawain ^a   Massa, Stephen M ^c  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b Prana Biotechnology   (Australia)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

C. elegans; metals; PBT2; R6 2

Indexed keywords

8 QUINOLINOL DERIVATIVE; PBT 2; POLYGLUTAMINE; UNCLASSIFIED DRUG; CLIOQUINOL; PBT2 COMPOUND;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR; BODY WEIGHT; BRAIN ATROPHY; BRAIN WEIGHT; CAENORHABDITIS ELEGANS; CONTROLLED STUDY; DRUG EFFICACY; HUNTINGTON CHOREA; LIFESPAN; MALE; MOTOR PERFORMANCE; NEMATODE; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN EXPRESSION; ROTAROD TEST; TASK PERFORMANCE; ANALOGS AND DERIVATIVES; ANIMAL; ATROPHY; CORPUS STRIATUM; DISEASE PREDISPOSITION; DOSE RESPONSE; DRUG EFFECTS; DRUG RESISTANCE; HUNTINGTON DISEASE; LONGEVITY; MOUSE; PATHOLOGY; PATHOPHYSIOLOGY; SPECIES DIFFERENCE; TRANSGENIC MOUSE;

ANIMALS; ATROPHY; CAENORHABDITIS ELEGANS; CLIOQUINOL; CORPUS STRIATUM; DISEASE SUSCEPTIBILITY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE; HUNTINGTON DISEASE; LONGEVITY; MICE; MICE, TRANSGENIC; MOTOR SKILLS; SPECIES SPECIFICITY;

EID: 84885372632     PISSN: 18796397     EISSN: 18796400     Source Type: Journal    
DOI: 10.3233/JHD-120029     Document Type: Article

References (43)

1. Kremer B, Goldberg P, Andrew SE, Theilmann J, Telenius H, et al. Aworldwide study of the Huntington's disease mutation: The sensitivity and specificity of measuring CAG repeats. N Eng J Med. 1994;330:1401-6.
2. Ravina B, Romer M, Constantinescu R, Biglan K, Brocht A, et al. The relationship between CAG repeat length and clinical progression in Huntington's disease. Mov Disord. 2008;23:1223-7.
3. Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, et al. Iron-export ferroxidase activity of beta-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. Cell. 2010;142:857-67.
4. Crouch PJ, Hung LW, Adlard PA, Cortes M, Lal V, et al. Increasing Cu bioavailability inhibits Abeta oligomers and tau phosphorylation. Proc Natl Acad Sci USA. 2009;106: 381-6.
5. Fox JH, Kama JA, Lieberman G, Chopra R, Dorsey K, et al. Mechanisms of copper ion mediated Huntington's disease progression. PLoS ONE. 2007;2:e334.
6. Fox J, Connor T, Stiles M, Kama J, Lu Z, et al. Cysteine oxidation within N-terminal mutant huntingtin promotes oligomerization and delays clearance of soluble protein. J Biol Chem. 2011;286:18320-30.
7. Rosas HD, Chen YI, Doros G, Salat DH, Chen N-k, et al. Alterations in brain transition metals in Huntington disease: An evolving and intricate story. Arch Neurol. 2012;69:887-93.
8. Tardiff DF, Tucci ML, Caldwell KA, Caldwell GA, Lindquist S. Different 8-hydroxyquinolines protect models of TDP-43 protein, α-Synuclein, and polyglutamine proteotoxicity through distinct mechanisms. J Biol Chem. 2012;287:4107-20.
9. Nguyen T, Hamby A, Massa SM (2005) Clioquinol downregulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model. Proc Natl Acad Sci U S A. 2005;102:11840-5. (Pubitemid 41170812)
10. Adlard PA, Cherny RA, Finkelstein DI, Gautier E, Robb E, et al. Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron. 2008;59: 43-55. (Pubitemid 351905863)
11. White AR, Du T, Laughton KM, Volitakis I, Sharples RA, et al. Degradation of the Alzheimer's disease amyloid beta peptide by metal-dependent up-regulation of metalloprotease activity. J Biol Chem. 2006;81:17670-17680. (Pubitemid 44035565)
12. Adlard PA, Parncutt JM, Finkelstein DI, Bush AI. Cognitive loss in zinc transporter-3 knock-out mice: A phenocopy for the synaptic and memory deficits of Alzheimer's disease? J Neurosci. 2010;30:1631-6.
13. Caragounis A, Du T, Fi GF, Laughton KM, Volitakis I, et al. Differential modulation of Alzheimer's disease amyloid beta-peptide accumulation by diverse classes of metal ligands. Biochemical Journal. 2007;407:435-50. (Pubitemid 350058477)
14. Adlard PA, Bica L, White AR, Nurjono M, Filiz G, et al. Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer's disease. PLoS ONE. 2011;6:e17669.
15. Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, et al. Genetic or pharmacological iron chelation prevents MPTPinduced neurotoxicity in vivo:Anovel therapy for Parkinson's disease. Neuron. 2003;37:899-909. (Pubitemid 36398297)
16. Faux NG, Ritchie CW, Gunn A, Rembach A, Tsatsanis A, et al. PBT2 rapidly improves cognition in Alzheimer's disease: Additional phase II analyses. Journal of Alzheimers Disease. 2010;20:509-16.
17. Lannfelt L, Blennow K, Zetterberg H, Batsman S, Ames D, et al. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer's disease: A phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2008;7:779-86.
18. Lannfelt L BK, Zetterberg H. [Errata] Safety, efficacy, and biomarker findings of PBT2 in targeting A beta as a modifying therapy for Alzheimer's disease: A phase IIa, double-blind, randomised, palcebo-controlled trial (Original publn: 2008:7;779). Lancet Neurol. 2009;8:981.
19. 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; 99:10417-22.
20. WoodW. The Nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press. Cold Spring Harbor, NY, USA, 1988.
21. Newcombe RG. Two-sided confidence intervals for the single proportion: Comparison of seven methods. Stat Med. 1998;17:857-72. (Pubitemid 28185165)
22. Gil JM, Mohapel P, Araujo IM, Popovic N, Li JY, et al. Reduced hippocampal neurogenesis in R6/2 transgenic Huntington's disease mice. Neurobiol Dis. 2005;20:744-51. (Pubitemid 41619351)
23. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell. 1996;87:493-506. (Pubitemid 26374323)
24. Hockly E,Woodman B, Mahal A, Lewis CM, Bates G. Standardization and statistical approaches to therapeutic trials in the R6/2 mouse. Brain Res Bull. 2003;61: 469-79. (Pubitemid 37117193)
25. Adlard PA, Bica L, White AR, Nurjono M, Filiz G, et al. Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer's disease. PLoS ONE. 2011;6:e17669.
26. Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med. 2004;10:148-54. (Pubitemid 38524884)
27. 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 Nat Acad Sci. 2002;99:10417-22.
28. Grossi C, Francese S, Casini A, Rosi MC, Luccarini I, et al. Clioquinol decreases Amyloid-beta burden and reducesworking memory impairment in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 2009.
29. Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits -amyloid accumulation in Alzheimer's disease transgenic mice. Neuron. 2001;30:665-76. (Pubitemid 32607332)
30. Fox JH, Kama JA, Lieberman G, Chopra R, Dorsey K, et al. Mechanisms of copper ion mediated Huntington's disease progression. PLoS ONE. 2007;2:e334.
31. Crouch PJ, Savva MS, Hung LW, Donnelly PS, Mot AI, et al. The Alzheimer's therapeutic PBT2 promotes amyloid- degradation andGSK3phosphorylation via ametal chaperone activity. J Neurochem. 2011;119:220-30.
32. van Ham TJ, Holmberg MA, van der Goot AT, Teuling E, Garcia-Arencibia M, et al. Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity. Cell. 2010;142: 601-12.
33. Kaletta T, Hengartner MO. Finding function in novel targets: C. elegans as a model organism. Nat Rev Drug Discov. 2006;5:387-99. (Pubitemid 43904931)
34. Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid [beta]-peptide. Nat Rev Mol Cell Biol. 2007;8:101-12. (Pubitemid 46432529)
35. Lajoie P, Snapp EL. Formation and toxicity of soluble polyglutamine oligomers in living cells. PLoS ONE. 2010;5: e15245.
36. Rammes G HA, Sroka K, Parsons CG. Aggregation inhibitors reverse -amyloid (A)-induced inhibition of long term potentiation (LTP) in murine hippoampal slices. Society for Neuroscience Washington DC. 2011.
37. Gil JM, Rego AC. The R6 lines of transgenic mice: A model for screening new therapies for Huntington's disease. Brain Res Rev. 2009;59:410-31.
38. Karpuj MV, Becher MW, Springer JE, Chabas D, Youssef S, et al. Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine. Nat Med. 2002;8:143-9. (Pubitemid 34155125)
39. Dedeoglu A, Kubilus JK, Yang L, Ferrante KL, Hersch SM, et al. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J Neurochem. 2003;85:1359-67. (Pubitemid 36702548)
40. Jin K, LaFevre-Bernt M, Sun Y, Chen S, Gafni J, et al. FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington's disease. Proc Natl Acad Sci USA. 2005;102:18189-94. (Pubitemid 41798523)
41. Ferrante RJ, Ryu H, Kubilus JK, D'Mello S, Sugars KL, et al. Chemotherapy for the brain: The antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's disease. J Neurosci. 2004;24:10335-42. (Pubitemid 39552617)
42. Ferrante RJ, Andreassen OA, Dedeoglu A, Ferrante KL, Jenkins BG, et al. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J Neurosci. 2002;22:1592-9. (Pubitemid 35386278)
43. Feigin A, Kieburtz K, Como P, Hickey C, Abwender D, et al. Assessment of coenzyme q10 tolerability in huntington's disease. Mov Disord. 1996;11:321-3. (Pubitemid 26138832)