Alzheimer's therapeutics targeting amyloid beta 1-42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits

PLoS ONE

Volumn 9, Issue 11, 2014, Pages

  Izzo, Nicholas J ^a   Staniszewski, Agnes ^g   To, Lillian ^d   Fa, Mauro ^g   Teich, Andrew F ^g   Saeed, Faisal ^g   Wostein, Harrison ^a   Walko, Thomas ^a   Vaswani, Anisha ^a   Wardius, Meghan ^a   Syed, Zanobia ^a   Ravenscroft, Jessica ^a   Mozzoni, Kelsie ^a   Silky, Colleen ^a   Rehak, Courtney ^a   Yurko, Raymond ^a   Finn, Patricia ^a   Look, Gary ^a   Rishton, Gilbert ^a   Safferstein, Hank ^a   Miller, Miles ^c   Johanson, Conrad ^c   Stopa, Edward ^c   Windisch, Manfred ^e   Hutter Paier, Birgit ^f   Shamloo, Mehrdad ^d   Arancio, Ottavio ^g   LeVine, Harry ^b   Catalano, Susan M ^a   more..

^a From Cognition Therapeutics Inc   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c BROWN UNIVERSITY   (United States)

^d STANFORD UNIVERSITY   (United States)

^e NeuroScios GmbH   (Austria)

^f QPS Austria GmbH   (Austria)

^g Department of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN[1-42]; AMYLOID BETA PROTEIN[1-42]OLIGOMER; AMYLOID BETA PROTEIN[1-42]OLIGOMER ANTAGONIST; CT 0093; CT 0109; CT 01202; CT 01206; CT 01344; CT 01346; NEW DRUG; OLIGOMER; PLACEBO; PROGESTERONE RECEPTOR; PROGESTERONE RECEPTOR MEMBRANE COMPONENT 1; RECEPTOR BLOCKING AGENT; SIGMA 2 OPIATE RECEPTOR; SYNAPTOPHYSIN; SYNTHETIC PEPTIDE; UNCLASSIFIED DRUG; AMYLOID BETA PROTEIN; AMYLOID BETA-PROTEIN (1-42); PEPTIDE FRAGMENT; PROTEIN BINDING;

ALZHEIMER DISEASE; ANIMAL BEHAVIOR; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; BRAIN CELL; CELL MEMBRANE TRANSPORT; COGNITIVE DEFECT; CONTROLLED STUDY; DENDRITIC SPINE; DOWN REGULATION; DRUG DETERMINATION; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SYNTHESIS; DRUG TARGETING; EC50; HUMAN; HUMAN TISSUE; IC50; IN VITRO STUDY; IN VIVO STUDY; LIGAND BINDING; MALE; MEMBRANE PERMEABILITY; MOUSE; MOUSE MODEL; NERVE CELL CULTURE; NERVE CELL PLASTICITY; NONHUMAN; OLIGOMERIZATION; PHENOTYPE; RAT; SYNAPTIC TRANSMISSION; TRANSGENIC MOUSE; ANIMAL; BRAIN; CHEMISTRY; COGNITION; COGNITION DISORDERS; DRUG DESIGN; DRUG EFFECTS; ENZYME LINKED IMMUNOSORBENT ASSAY; GLIA; MEDICINAL CHEMISTRY; METABOLISM; NERVE CELL; PROTEIN TRANSPORT; SPRAGUE DAWLEY RAT; SYNAPSE;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; BRAIN; CHEMISTRY, PHARMACEUTICAL; COGNITION; COGNITION DISORDERS; DRUG DESIGN; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; MICE; MICE, TRANSGENIC; NEUROGLIA; NEURONS; PEPTIDE FRAGMENTS; PROTEIN BINDING; PROTEIN TRANSPORT; RATS; RATS, SPRAGUE-DAWLEY; SYNAPSES;

EID: 84911495459     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0111898     Document Type: Article

References (74)

1. Haes AJ, Chang L, Klein WL, Van Duyne RP (2005) Detection of a biomarker for Alzheimer's disease from synthetic and clinical samples using a nanoscale optical biosensor. J Am Chem Soc 127: 2264-2271.
2. Tomic JL, Pensalfini A, Head E, Glabe CG (2009) Soluble fibrillar oligomer levels are elevated in Alzheimer's disease brain and correlate with cognitive dysfunction. Neurobiol Dis 35: 352-358.
3. Bao F, Wicklund L, Lacor PN, Klein WL, Nordberg A, et al. (2012) Different beta-amyloid oligomer assemblies in Alzheimer brains correlate with age of disease onset and impaired cholinergic activity. Neurobiol Aging 33: 825 e821- 813.
4. Esparza TJ, Zhao H, Cirrito JR, Cairns NJ, Bateman RJ, et al. (2013) Amyloidbeta oligomerization in Alzheimer dementia versus high-pathology controls. Ann Neurol 73: 104-119.
5. Yang T, Hong S, O'Malley T, Sperling RA, Walsh DM, et al. (2013) New ELISAs with high specificity for soluble oligomers of amyloid beta-protein detect natural Abeta oligomers in human brain but not CSF. Alzheimers Dement 9: 99-112.
6. Herskovits AZ, Locascio JJ, Peskind ER, Li G, Hyman BT (2013) A Luminex assay detects amyloid beta oligomers in Alzheimer's disease cerebrospinal fluid. PLoS One 8: e67898.
7. Kim T, Vidal GS, Djurisic M, William CM, Birnbaum ME, et al. (2013) Human LilrB2 Is a &beta-Amyloid Receptor and Its Murine Homolog PirB Regulates Synaptic Plasticity in an Alzheimer's Model. Science 341: 1399-1404.
8. Cisse M, Halabisky B, Harris J, Devidze N, Dubal DB, et al. (2011) Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature 469: 47-52.
9. Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457: 1128-1132.
10. Masuda-Suzukake M, Nonaka T, Hosokawa M, Oikawa T, Arai T, et al. (2013) Prion-like spreading of pathological alpha-synuclein in brain. Brain 136: 1128-1138.
11. Um JW, Kaufman AC, Kostylev M, Heiss JK, Stagi M, et al. (2013)Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer abeta oligomer bound to cellular prion protein. Neuron 79: 887-902.
12. Kessels HW, Nabavi S, Malinow R (2013) Metabotropic NMDA receptor function is required for beta-amyloid-induced synaptic depression. Proc Natl Acad Sci U S A 110: 4033-4038.
13. Renner M, Lacor PN, Velasco PT, Xu J, Contractor A, et al. (2010) Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5.Neuron 66: 739-754.
14. Lesne SE, Sherman MA, Grant M, Kuskowski M, Schneider JA, et al. (2013)Brain amyloid-beta oligomers in ageing and Alzheimer's disease. Brain 136: 1383-1398.
15. Kam TI, Song S, Gwon Y, Park H, Yan JJ, et al. (2013) FcgammaRIIb mediates amyloid-beta neurotoxicity and memory impairment in Alzheimer's disease. J Clin Invest 123: 2791-2802.
16. Ferreira IL, Bajouco LM, Mota SI, Auberson YP, Oliveira CR, et al. (2012)Amyloid beta peptide 1-42 disturbs intracellular calcium homeostasis through activation of GluN2B-containing N-methyl-d-aspartate receptors in cortical cultures. Cell Calcium 51: 95-106.
17. Zempel H, Luedtke J, Kumar Y, Biernat J, Dawson H, et al. (2013) Amyloidbeta oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin. EMBO J 32: 2920-2937.
18. Zempel H, Mandelkow EM (2012) Linking amyloid-beta and tau: amyloid-beta induced synaptic dysfunction via local wreckage of the neuronal cytoskeleton. Neurodegener Dis 10: 64-72.
19. Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, et al. (2004) Synaptic targeting by Alzheimer's-related amyloid beta oligomers. J Neurosci 24: 10191-10200.
20. Hsieh H, Boehm J, Sato C, Iwatsubo T, Tomita T, et al. (2006) AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 52: 831-843.
21. Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, et al. (2007)Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J Neurosci 27: 796-807.
22. Shrestha BR, Vitolo OV, Joshi P, Lordkipanidze T, Shelanski M, et al. (2006)Amyloid beta peptide adversely affects spine number and motility in hippocampal neurons. Mol Cell Neurosci 33: 274-282.
23. Calabrese B, Shaked GM, Tabarean IV, Braga J, Koo EH, et al. (2007) Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturallysecreted amyloid-beta protein. Mol Cell Neurosci 35: 183-193.
24. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, et al. (2007)Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci 27: 2866-2875.
25. Wei W, Nguyen LN, Kessels HW, Hagiwara H, Sisodia S, et al. (2010) Amyloid beta from axons and dendrites reduces local spine number and plasticity. Nat Neurosci 13: 190-196.
26. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, et al. (2005)Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci 8: 79-84.
27. Klyubin I, Wang Q, Reed MN, Irving EA, Upton N, et al. (2011) Protection against Abeta-mediated rapid disruption of synaptic plasticity and memory by memantine. Neurobiol Aging 32: 614-623.
28. Catalano SM, Dodson EC, Henze DA, Joyce JG, Krafft GA, et al. (2006) The role of amyloid-beta derived diffusible ligands (ADDLs) in Alzheimer's disease. Curr Top Med Chem 6: 597-608.
29. Marcello E, Epis R, Di Luca M (2008) Amyloid flirting with synaptic failure: towards a comprehensive view of Alzheimer's disease pathogenesis. Eur J Pharmacol 585: 109-118.
30. Viola KL, Velasco PT, Klein WL (2008) Why Alzheimer's is a disease of memory: the attack on synapses by A beta oligomers (ADDLs). J Nutr Health Aging 12: 51S-57S.
31. Shankar GM, Leissring MA, Adame A, Sun X, Spooner E, et al. (2009)Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life. Neurobiol Dis 36: 293-302.
32. Benilova I, De Strooper B (2013) Promiscuous Alzheimer's Amyloid: Yet Another Partner. Science 341: 1354-1355.
33. Klein WL (2002) Abeta toxicity in Alzheimer's disease: globular oligomers (ADDLs) as new vaccine and drug targets. Neurochem Int 41: 345-352.
34. Lambert MP, Viola KL, Chromy BA, Chang L, Morgan TE, et al. (2001)Vaccination with soluble Abeta oligomers generates toxicity-neutralizing antibodies. J Neurochem 79: 595-605.
35. Faul F, Erdfelder E, Lang AG, Buchner A (2007) G Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39: 175-191.
36. Puzzo D, Privitera L, Leznik E, Fa M, Staniszewski A, et al. (2008) Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci 28: 14537-14545.
37. Havas D, Hutter-Paier B, Ubhi K, Rockenstein E, Crailsheim K, et al. (2011) A longitudinal study of behavioral deficits in an AbetaPP transgenic mouse model of Alzheimer's disease. J Alzheimers Dis 25: 231-243.
38. Faizi M, Bader PL, Saw N, Nguyen TV, Beraki S, et al. (2012) Thy1- hAPP(Lond/Swe +) mouse model of Alzheimer's disease displays broad behavioral deficits in sensorimotor, cognitive and social function. Brain Behav 2: 142-154.
39. LeVine H III (2004) Alzheimer's beta-peptide oligomer formation at physiologic concentrations. Anal Biochem 335: 81-90.
40. Ganapathy ME, Prasad PD, Huang W, Seth P, Leibach FH, et al. (1999)Molecular and ligand-binding characterization of the sigma-receptor in the Jurkat human T lymphocyte cell line. J Pharmacol Exp Ther 289: 251-260.
41. Torre V, Nicholls J (1998) Neural circuits and networks. Berlin; New York: Springer. viii, 247 p. p.
42. Kaech S, Banker G (2006) Culturing hippocampal neurons. Nat Protoc 1: 2406-2415.
43. Sharma K, Fong DK, Craig AM (2006) Postsynaptic protein mobility in dendritic spines: long-term regulation by synaptic NMDA receptor activation. Mol Cell Neurosci 31: 702-712.
44. Gortz P, Fleischer W, Rosenbaum C, Otto F, Siebler M (2004) Neuronal network properties of human teratocarcinoma cell line-derived neurons. Brain Res 1018: 18-25.
45. Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, et al. (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440: 352-357.
46. Brody DL, Magnoni S, Schwetye KE, Spinner ML, Esparza TJ, et al. (2008) Amyloid-beta dynamics correlate with neurological status in the injured human brain. Science 321: 1221-1224.
47. Walsh DM, Teplow DB (2012) Alzheimer's disease and the amyloid betaprotein. Prog Mol Biol Transl Sci 107: 101-124.
48. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, et al. (2008) Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 14: 837-842.
49. Tseng BP, Esler WP, Clish CB, Stimson ER, Ghilardi JR, et al. (1999)Deposition of monomeric, not oligomeric, Abeta mediates growth of Alzheimer's disease amyloid plaques in human brain preparations. Biochemistry 38: 10424-10431.
50. rd ed. Totowa, N.J.: Humana Press. pp. 255.
51. Liu Y, Schubert D (1997) Cytotoxic Amyloid Peptides Inhibit Cellular 3- (4,5- Dimethylthiazol-2-yl) -2,5-Diphenyltetrazolium Bromide (MTT) Reduction by Enhancing MTT Formazan Exocytosis. J Neurochem 69.
52. Hong HS, Maezawa I, Yao N, Xu B, Diaz-Avalos R, et al. (2007) Combining the Rapid MTT Formazan Exocytosis Assay and the MC65 Protection Assay Led to the Discovery of Carbazole Analogs as Small-Molecule Inhibitors of Ab Oligomer-Induced Cytotoxicity. Brain Res 1130: 223-234.
53. Kreutzmann P, Wolf G, Kupsch K (2010) Minocycline recovers MTT-formazan exocytosis impaired by amyloid beta peptide. Cell Mol Neurobiol 30: 979-984.
54. Fenili D, Brown M, Rappaport R, McLaurin J (2007) Properties of scyllo-inositol as a therapeutic treatment of AD-like pathology. J Mol Med (Berl) 85: 603-611.
55. Kornhuber J, Quack G (1995) Cerebrospinal fluid and serum concentrations of the N-methyl-D-aspartate (NMDA) receptor antagonist memantine in man. Neurosci Lett 195: 137-139.
56. Zhang JH, Chung TD, Oldenburg KR (1999) A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J Biomol Screen 4: 67-73.
57. Weidner AM, Housley M, Murphy MP, LeVine H III (2011) Purified high molecular weight synthetic Abeta (1-42) and biological Abeta oligomers are equipotent in rapidly inducing MTT formazan exocytosis. Neurosci Lett 497: 1-5.
58. Lambert MP, Velasco PT, Chang L, Viola KL, Fernandez S, et al. (2007)Monoclonal antibodies that target pathological assemblies of Abeta. J Neurochem 100: 23-35.
59. Yamamoto N, Matsubara E, Maeda S, Minagawa H, Takashima A, et al. (2007) A ganglioside-induced toxic soluble Abeta assembly. Its enhanced formation from Abeta bearing the Arctic mutation. J Biol Chem 282: 2646-2655.
60. Reed MN, Hofmeister JJ, Jungbauer L, Welzel AT, Yu C, et al. (2011) Cognitive effects of cell-derived and synthetically derived Abeta oligomers. Neurobiol Aging 32: 1784-1794.
61. Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging 27: 1372-1384.
62. Puzzo D, Vitolo O, Trinchese F, Jacob JP, Palmeri A, et al. (2005) Amyloid-beta peptide inhibits activation of the nitric oxide/cGMP/cAMP-responsive elementbinding protein pathway during hippocampal synaptic plasticity. J Neurosci 25: 6887-6897.
63. Takeda S, Hashimoto T, Roe AD, Hori Y, Spires-Jones TL, et al. (2013) Brain interstitial oligomeric amyloid beta increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease. FASEB J. 27: 3239-3248.
64. Rockenstein E, Mallory M, Mante M, Sisk A, Masliaha E (2001) Early formation of mature amyloid-beta protein deposits in a mutant APP transgenicmodel depends on levels of Abeta(1-42). Journal of Neuroscience Research 66: 573-582.
65. Izzo NJ, Xu J, Zeng C, Kirk M, Mozzoni K, et al. (2014) Alzheimer's therapeutics targeting Amyloid beta 1-42 oligomers II: Sigma-2/PGRMC1receptors mediate Abeta 42 oligomer binding and synaptotoxicity. PLoS ONE 10: e0111899.
66. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, et al. (2003) APP processing and synaptic function. Neuron 37: 925-937.
67. Maezawa I, Hong HS, Wu HC, Battina SK, Rana S, et al. (2006) A novel tricyclic pyrone compound ameliorates cell death associated with intracellular amyloid-beta oligomeric complexes. J Neurochem 98: 57-67.
68. Liu Y, Dargusch R, Banh C, Miller CA, Schubert D (2004) Detecting bioactive amyloid beta peptide species in Alzheimer's disease. J Neurochem 91: 648-656.
69. Rana S, Hong HS, Barrigan L, Jin LW, Hua DH (2009) Syntheses of tricyclic pyrones and pyridinones and protection of Abeta-peptide induced MC65neuronal cell death. Bioorg Med Chem Lett 19: 670-674.
70. Hong HS, Rana S, Barrigan L, Shi A, Zhang Y, et al. (2009) Inhibition of Alzheimer's amyloid toxicity with a tricyclic pyrone molecule in vitro and in vivo. J Neurochem 108: 1097-1108.
71. Ronicke R, Klemm A, Meinhardt J, Schroder UH, Fandrich M, et al. (2008)Abeta mediated diminution of MTT reduction-an artefact of single cell culture? PLoS One 3: e3236.
72. Tong L, Balazs R, Thornton PL, Cotman CW (2004) Beta-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons. J Neurosci 24: 6799-6809.
73. Lesne SE (2013) Breaking the Code of Amyloid- Oligomers. Int J Cell Biol 2013: 950783.
74. Fowler SW, Chiang AC, Savjani RR, Larson ME, Sherman MA, et al. (2014)Genetic Modulation of Soluble Abeta Rescues Cognitive and Synaptic Impairment in a Mouse Model of Alzheimer's Disease. J Neurosci 34: 7871-7885.