Neuroscience: An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Ab42 aggregates linked with Alzheimer's disease

Science Advances

Volumn 2, Issue 2, 2016, Pages

  Habchi, Johnny ^a   Arosio, Paolo ^a   Perni, Michele ^a   Costa, Ana Rita ^a   Yagi Utsumi, Maho ^a   Joshi, Priyanka ^a   Chia, Sean ^a   Cohen, Samuel I A ^a   Müller, Martin B D ^b   Linse, Sara ^c   Nollen, Ellen A A ^b   Dobson, Christopher M ^a   Knowles, Tuomas P J ^a   Vendruscolo, Michele ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^c LUND UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

AGGREGATES; CHEMICAL ANALYSIS; NUCLEATION; SELF ASSEMBLY;

ALZHEIMER'S DISEASE; CAENORHABDITIS ELEGANS; FOOD AND DRUG ADMINISTRATION; MOLECULAR MECHANISM; NEUROBLASTOMA CELLS; NEURODEGENERATIVE DISORDERS; PRIMARY NUCLEATION; THERAPEUTIC AGENTS;

NEURODEGENERATIVE DISEASES;

AMYLOID BETA PROTEIN; AMYLOID BETA-PROTEIN (1-42); ANTINEOPLASTIC AGENT; BEXAROTENE; HOMOTAURINE; PEPTIDE FRAGMENT; RECOMBINANT PROTEIN; TAURINE; TETRALIN DERIVATIVE;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; ANALOGS AND DERIVATIVES; ANIMAL; ANIMAL MODEL; CAENORHABDITIS ELEGANS; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; GENETICS; HUMAN; IN VITRO STUDY; KINETICS; METABOLISM; MOLECULAR GENETICS; PROCEDURES; PROTEIN MULTIMERIZATION; TRANSGENIC ANIMAL;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; AMYLOID BETA-PEPTIDES; ANIMALS; ANIMALS, GENETICALLY MODIFIED; ANTINEOPLASTIC AGENTS; CAENORHABDITIS ELEGANS; DRUG DISCOVERY; HUMANS; IN VITRO TECHNIQUES; KINETICS; MODELS, ANIMAL; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; PROTEIN MULTIMERIZATION; RECOMBINANT PROTEINS; TAURINE; TETRAHYDRONAPHTHALENES;

EID: 84961154608     PISSN: None     EISSN: 23752548     Source Type: Journal    
DOI: 10.1126/sciadv.1501244     Document Type: Article

References (53)

1. Alzheimer's Association, 2012 Alzheimer's disease facts and figures. Alzheimer's Dement. 8, 131-168 (2012).
2. F. Chiti, C. M. Dobson, Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem. 75, 333-366 (2006).
3. C. M. Dobson, Protein folding and misfolding. Nature 426, 884-890 (2003).
4. D. J. Selkoe, Folding proteins in fatal ways. Nature 426, 900-904 (2003).
5. C. Haass, D. J. Selkoe, Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid b-peptide. Nat. Rev. Mol. Cell Biol. 8, 101-112 (2007).
6. W. E. Balch, R. I. Morimoto, A. Dillin, J. W. Kelly, Adapting proteostasis for disease intervention. Science 319, 916-919 (2008).
7. F. U. Hartl, A. Bracher, M. Hayer-Hartl, Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332 (2011).
8. D. Eisenberg, M. Jucker, The amyloid state of proteins in human diseases. Cell 148, 1188-1203 (2012).
9. T. P. J. Knowles, M. Vendruscolo, C. M. Dobson, The amyloid state and its association with protein misfolding diseases. Nat. Rev. Mol. Cell Biol. 15, 384-396 (2014).
10. J. Habchi, P. Tompa, S. Longhi, V. N. Uversky, Introducing protein intrinsic disorder. Chem. Rev. 114, 6561-6588 (2014).
11. J. Bieschke, Natural compounds may open new routes to treatment of amyloid diseases. Neurotherapeutics 10, 429-439 (2013).
12. J. Chen, A. H. Armstrong, A. N. Koehler, M. H. Hecht, Small molecule microarrays enable the discovery of compounds that bind the Alzheimer's Ab peptide and reduce its cytotoxicity. J. Am. Chem. Soc. 132, 17015-17022 (2010).
13. M. Ito, J. Johansson, R. Strömberg, L. Nilsson, Effects of ligands on unfolding of the amyloid b-peptide central helix: Mechanistic insights from molecular dynamics simulations. PLOS One 7, e30510 (2012).
14. H. Kroth, A. Ansaloni, Y. Varisco, A. Jan, N. Sreenivasachary, N. Rezaei-Ghaleh, V. Giriens, S. Lohmann, M. P. López-Deber, O. Adolfsson, M. Pihlgren, P. Paganetti, W. Froestl, L. Nagel-Steger, D. Willbold, T. Schrader, M. Zweckstetter, A. Pfeifer, H. A. Lashuel, A. Muhs, Discovery and structure activity relationship of small molecule inhibitors of toxic b-amyloid-42 fibril formation. J. Biol. Chem. 287, 34786-34800 (2012).
15. M. Necula, R. Kayed, S. Milton, C. G. Glabe, Small molecule inhibitors of aggregation indicate that amyloid b oligomerization and fibrillization pathways are independent and distinct. J. Biol. Chem. 282, 10311-10324 (2007).
16. Q. Nie, X. Du, M. Geng, Small molecule inhibitors of amyloid b peptide aggregation as a potential therapeutic strategy for Alzheimer's disease. Acta Pharmacol. Sin. 32, 545-551 (2011).
17. Y. Porat, A. Abramowitz, E. Gazit, Inhibition of amyloid fibril formation by polyphenols: Structural similarity and aromatic interactions as a common inhibition mechanism. Chem. Biol. Drug Des. 67, 27-37 (2006).
18. S. Sinha, D. H. J. Lopes, Z. Du, E. S. Pang, A. Shanmugam, A. Lomakin, P. Talbiersky, A. Tennstaedt, K. McDaniel, R. Bakshi, P.-Y. Kuo, M. Ehrmann, G. B. Benedek, J. A. Loo, F.-G. Klärner, T. Schrader, C. Wang, G. Bitan, Lysine-specific molecular tweezers are broad-spectrum inhibitors of assembly and toxicity of amyloid proteins. J. Am. Chem. Soc. 133, 16958-16969 (2011).
19. A. Abelein, L. Lang, C. Lendel, A. Gräslund, J. Danielsson, Transient small molecule interactions kinetically modulate amyloid b peptide self-assembly. FEBS Lett. 586, 3991-3995 (2012).
20. P. T. Lansbury, H. A. Lashuel, A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature 443, 774-779 (2006).
21. J. L. Cummings, T. Morstorf, K. Zhong, Alzheimer's disease drug-development pipeline: Few candidates, frequent failures. Alzheimer's Res. Ther. 6, 37 (2014).
22. P. Arosio, R. Cukalevski, B. Frohm, T. P. J. Knowles, S. Linse, Quantification of the concentration of Ab42 propagons during the lag phase by an amyloid chain reaction assay. J. Am. Chem. Soc. 136, 219-225 (2014).
23. S. M. Butterfield, H. A. Lashuel, Amyloidogenic protein-membrane interactions: Mechanistic insight from model systems. Angew. Chem. Int. Ed. 49, 5628-5654 (2010).
24. S. Campioni, B. Mannini, M. Zampagni, A. Pensalfini, C. Parrini, E. Evangelisti, A. Relini, M. Stefani, C. M. Dobson, C. Cecchi, F. Chiti, A causative link between the structure of aberrant protein oligomers and their toxicity. Nat. Chem. Biol. 6, 140-147 (2010).
25. G. M. Shankar, S. Li, T. H. Mehta, A. Garcia-Munoz, N. E. Shepardson, I. Smith, F. M. Brett, M. A. Farrell, M. J. Rowan, C. A. Lemere, C. M. Regan, D. M. Walsh, B. L. Sabatini, D. J. Selkoe, Amyloid-b protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 14, 837-842 (2008).
26. D. M. Walsh, D. J. Selkoe, Ab oligomers-A decade of discovery. J. Neurochem. 101, 1172-1184 (2007).
27. B. Mannini, E. Mulvihill, C. Sgromo, R. Cascella, R. Khodarahmi, M. Ramazzotti, C. M. Dobson, C. Cecchi, F. Chiti, Toxicity of protein oligomers is rationalized by a function combining size and surface hydrophobicity. ACS Chem. Biol. 9, 2309-2317 (2014).
28. P. Arosio, M. Vendruscolo, C. M. Dobson, T. P. J. Knowles, Chemical kinetics for drug discovery to combat protein aggregation diseases. Trends Pharmacol. Sci. 35, 127-135 (2014).
29. T. P. J. Knowles, C. A. Waudby, G. L. Devlin, S. I. A. Cohen, A. Aguzzi, M. Vendruscolo, E. M. Terentjev, M. E. Welland, C. M. Dobson, An analytical solution to the kinetics of breakable filament assembly. Science 326, 1533-1537 (2009).
30. S. I. A. Cohen, S. Linse, L. M. Luheshi, E. Hellstrand, D. A. White, L. Rajah, D. E. Otzen, M. Vendruscolo, C. M. Dobson, T. P. J. Knowles, Proliferation of amyloid-b42 aggregates occurs through a secondary nucleation mechanism. Proc. Natl. Acad. Sci. U. S. A. 110, 9758-9763 (2013).
31. E. Hellstrand, B. Boland, D. M. Walsh, S. Linse, Amyloid b-protein aggregation produces highly reproducible kinetic data and occurs by a two-phase process. ACS Chem. Neurosci. 1, 13-18 (2010).
32. S. I. A. Cohen, M. Vendruscolo, C. M. Dobson, T. P. J. Knowles, From macroscopic measurements to microscopic mechanisms of protein aggregation. J. Mol. Biol. 421, 160-171 (2012).
33. P. J. Hajduk, W. R. J. D. Galloway, D. R. Spring, Drug discovery: A question of library design. Nature 470, 42-43 (2011).
34. D. C. Rees, M. Congreve, C. W. Murray, R. Carr, Fragment-based lead discovery. Nat. Rev. Drug Discov. 3, 660-672 (2004).
35. B. S. Appleby, J. L. Cummings, Discovering new treatments for Alzheimer's disease by repurposing approved medications. Curr. Top. Med. Chem. 13, 2306-2327 (2013).
36. A. Corbett, G. Williams, C. Ballard, Drug repositioning: An opportunity to develop novel treatments for Alzheimer's disease. Pharmaceuticals 6, 1304-1321 (2013).
37. C. Caltagirone, L. Ferrannini, N. Marchionni, G. Nappi, G. Scapagnini, M. Trabucchi, The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: A review. Aging Clin. Exp. Res. 24, 580-587 (2012).
38. V. Bomben, J. Holth, J. Reed, P. Cramer, G. Landreth, J. Noebels, Bexarotene reduces network excitability in models of Alzheimer's disease and epilepsy. Neurobiol. Aging 35, 2091-2095 (2014).
39. P. E. Cramer, J. R. Cirrito, D. W. Wesson, C. Y. D. Lee, J. C. Karlo, A. E. Zinn, B. T. Casali, J. L. Restivo, W. D. Goebel, M. J. James, K. R. Brunden, D. A. Wilson, G. E. Landreth, ApoE-directed therapeutics rapidly clear b-amyloid and reverse deficits in AD mouse models. Science 335, 1503-1506 (2012).
40. N. F. Fitz, A. A. Cronican, I. Lefterov, R. Koldamova, Comment on "ApoE-directed therapeutics rapidly clear b-amyloid and reverse deficits in AD mouse models". Science 340, 924-c (2013).
41. A. R. Price, G. Xu, Z. B. Siemienski, L. A. Smithson, D. R. Borchelt, T. E. Golde, K. M. Felsenstein, Comment on "ApoE-directed therapeutics rapidly clear b-amyloid and reverse deficits in AD mouse models". Science 340, 924-d (2013).
42. I. Tesseur, A. C. Lo, A. Roberfroid, S. Dietvorst, B. Van Broeck, M. Borgers, H. Gijsen, D. Moechars, M. Mercken, J. Kemp, R. D'Hooge, B. De Strooper, Comment on "ApoEdirected therapeutics rapidly clear b-amyloid and reverse deficits in AD mouse models". Science 340, 924-e (2013).
43. K. Veeraraghavalu, C. Zhang, S. Miller, J. K. Hefendehl, T. W. Rajapaksha, J. Ulrich, M. Jucker, D. M. Holtzman, R. E. Tanzi, R. Vassar, S. S. Sisodia, Comment on "ApoE-directed therapeutics rapidly clear b-amyloid and reverse deficits in AD mouse models". Science 340, 924-f (2013).
44. K. D. LaClair, K. F. Manaye, D. L. Lee, J. S. Allard, A. V. Savonenko, J. C. Troncoso, P. C. Wong, Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice. Mol. Neurodegener. 8, 18 (2013).
45. J. Fantini, C. Di Scala, N. Yahi, J.-D. Troadec, K. Sadelli, H. Chahinian, N. Garmy, Bexarotene blocks calcium-permeable ion channels formed by neurotoxic Alzheimer's b-amyloid peptides. ACS Chem. Neurosci. 5, 216-224 (2014).
46. G. McColl, B. R. Roberts, T. L. Pukala, V. B. Kenche, C. M. Roberts, C. D. Link, T. M. Ryan, C. L. Masters, K. J. Barnham, A. I. Bush, R. A. Cherny, Utility of an improved model of amyloid-beta (Ab1-42) toxicity in Caenorhabditis elegans for drug screening for Alzheimer's disease. Mol. Neurodegener. 7, 57 (2012).
47. H. Olzscha, S. M. Schermann, A. C. Woerner, S. Pinkert, M. H. Hecht, G. G. Tartaglia, M. Vendruscolo, M. Hayer-Hartl, F. U. Hartl, R. M. Vabulas, Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions. Cell 144, 67-78 (2011).
48. S. I. A. Cohen, P. Arosio, J. Presto, F. R. Kurudenkandy, H. Biverstål, L. Dolfe, C. Dunning, X. Yang, B. Frohm, M. Vendruscolo, J. Johansson, C. M. Dobson, A. Fisahn, T. P. J. Knowles, S. Linse, A molecular chaperone breaks the catalytic cycle that generates toxic Ab oligomers. Nat. Struct. Mol. Biol. 22, 207-213 (2015).
49. R. A. Sperling, P. S. Aisen, L. A. Beckett, D. A. Bennett, S. Craft, A. M. Fagan, T. Iwatsubo, C. R. Jack Jr., J. Kaye, T. J. Montine, D. C. Park, E. M. Reiman, C. C. Rowe, E. Siemers, Y. Stern, K. Yaffe, M. C. Carrillo, B. Thies, M. Morrison-Bogorad, M. V. Wagster, C. H. Phelps, Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's Dement. 7, 280-292 (2011).
50. D. J. Selkoe, Resolving controversies on the path to Alzheimer's therapeutics. Nat. Med. 17, 1060-1065 (2011).
51. D. M. Walsh, E. Thulin, A. M. Minogue, N. Gustavsson, E. Pang, D. B. Teplow, S. Linse, A facile method for expression and purification of the Alzheimer's disease-associated amyloid b-peptide. FEBS J. 276, 1266-1281 (2009).
52. R. Roychaudhuri, M. Yang, M. M. Hoshi, D. B. Teplow, Amyloid b-protein assembly and Alzheimer disease. J. Biol. Chem. 284, 4749-4753 (2009).
53. S. Brenner, The genetics of Caenorhabditis elegans. Genetics 77, 71-94 (1974).