α-Synuclein Immunotherapy Blocks Uptake and Templated Propagation of Misfolded α-Synuclein and Neurodegeneration

Cell Reports

Volumn 7, Issue 6, 2014, Pages 2054-2065

  Tran, Hien T ^a,b   Chung, CharlotteHiu Yan ^a   Iba, Michiyo ^a   Zhang, Bin ^a   Trojanowski, John Q ^a   Luk, Kelvin C ^a   Lee, Virginia M Y ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b ISIS PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; IMMUNOGLOBULIN G; MONOCLONAL ANTIBODY; SYN303 MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY SPECIFICITY; ARTICLE; BRAIN DISEASE; CELL DEATH; CELL LOSS; CONTROLLED STUDY; DOPAMINERGIC NERVE CELL; DRUG BLOOD LEVEL; DRUG EFFICACY; IMMUNOTHERAPY; IN VIVO STUDY; LEWY BODY; LEWY NEURITE; MOUSE; NERVE CELL; NERVE CELL CULTURE; NERVE DEGENERATION; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PREFORMED FIBRIL; PRIORITY JOURNAL; PROTEIN MISFOLDING; PROTEIN STRUCTURE; PROTEIN TARGETING; SUBSTANTIA NIGRA; SYNAPSE; ANIMAL; FEMALE; IMMUNOLOGY; LEWY BODY DISEASE; MALE; PARKINSON DISEASE; PATHOLOGY; PROCEDURES;

MUS;

ALPHA-SYNUCLEIN; ANIMALS; ANTIBODIES, MONOCLONAL; FEMALE; IMMUNOTHERAPY; LEWY BODY DISEASE; MALE; MICE; NEURONS; PARKINSON DISEASE;

EID: 84903441419     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2014.05.033     Document Type: Article

References (35)

1. Bae E.J., Lee H.J., Rockenstein E., Ho D.H., Park E.B., Yang N.Y., Desplats P., Masliah E., Lee S.J. Antibody-aided clearance of extracellular α-synuclein prevents cell-to-cell aggregate transmission. J.Neurosci. 2012, 32:13454-13469.
2. Boutajangout A., Ingadottir J., Davies P., Sigurdsson E.M. Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brain. J.Neurochem. 2011, 118:658-667.
3. Braak H., Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991, 82:239-259.
4. Braak H., Del Tredici K., Rüb U., de Vos R.A., Jansen Steur E.N., Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol. Aging 2003, 24:197-211.
5. Costanzo M., Zurzolo C. The cell biology of prion-like spread ofprotein aggregates: mechanisms and implication in neurodegeneration. Biochem. J. 2013, 452:1-17.
6. d'Abramo C., Acker C.M., Jimenez H.T., Davies P. Tau passive immunotherapy in mutant P301L mice: antibody affinity versus specificity. PLoS ONE 2013, 8:e62402.
7. Demattos R.B., Lu J., Tang Y., Racke M.M., Delong C.A., Tzaferis J.A., Hole J.T., Forster B.M., McDonnell P.C., Liu F., et al. A plaque-specific antibody clears existing β-amyloid plaques in Alzheimer's disease mice. Neuron 2012, 76:908-920.
8. Duda J.E., Giasson B.I., Mabon M.E., Lee V.M., Trojanowski J.Q. Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseases. Ann. Neurol. 2002, 52:205-210.
9. Giasson B.I., Jakes R., Goedert M., Duda J.E., Leight S., Trojanowski J.Q., Lee V.M. A panel of epitope-specific antibodies detects protein domains distributed throughout human α-synuclein in Lewy bodies of Parkinson's disease. J.Neurosci. Res. 2000, 59:528-533.
10. Giasson B.I., Duda J.E., Murray I.V., Chen Q., Souza J.M., Hurtig H.I., Ischiropoulos H., Trojanowski J.Q., Lee V.M. Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science 2000, 290:985-989.
11. Giasson B.I., Duda J.E., Quinn S.M., Zhang B., Trojanowski J.Q., Lee V.M. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 2002, 34:521-533.
12. Gros-Louis F., Soucy G., Larivière R., Julien J.P. Intracerebroventricular infusion of monoclonal antibody or its derived Fab fragment against misfolded forms of SOD1 mutant delays mortality in a mouse model of ALS. J.Neurochem. 2010, 113:1188-1199.
13. Guo J.L., Lee V.M. Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat. Med. 2014, 20:130-138.
14. Guo J.L., Covell D.J., Daniels J.P., Iba M., Stieber A., Zhang B., Riddle D.M., Kwong L.K., Xu Y., Trojanowski J.Q., Lee V.M. Distinct α-synuclein strains differentially promote tau inclusions in neurons. Cell 2013, 154:103-117.
15. Irwin D.J., White M.T., Toledo J.B., Xie S.X., Robinson J.L., Van Deerlin V., Lee V.M., Leverenz J.B., Montine T.J., Duda J.E., et al. Neuropathologic substrates of Parkinson disease dementia. Ann. Neurol. 2012, 72:587-598.
16. Jiang P., Gan M., Yen S.H. Dopamine prevents lipid peroxidation-induced accumulation of toxic α-synuclein oligomers by preserving autophagy-lysosomal function. Front. Cell. Neurosci. 2013, 7:81.
17. Kfoury N., Holmes B.B., Jiang H., Holtzman D.M., Diamond M.I. Trans-cellular propagation of Tau aggregation by fibrillar species. J.Biol. Chem. 2012, 287:19440-19451.
18. Kordower J.H., Chu Y., Hauser R.A., Freeman T.B., Olanow C.W. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat. Med. 2008, 14:504-506.
19. Lemere C.A., Masliah E. Can Alzheimer disease be prevented by amyloid-β immunotherapy?. Nat. Rev. Neurol. 2010, 6:108-119.
20. Li J.Y., Englund E., Holton J.L., Soulet D., Hagell P., Lees A.J., Lashley T., Quinn N.P., Rehncrona S., Björklund A., et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat. Med. 2008, 14:501-503.
21. Lim Y., Kehm V.M., Lee E.B., Soper J.H., Li C., Trojanowski J.Q., Lee V.M. α-Syn suppression reverses synaptic and memory defects in a mouse model of dementia with Lewy bodies. J.Neurosci. 2011, 31:10076-10087.
22. Luk K.C., Song C., O'Brien P., Stieber A., Branch J.R., Brunden K.R., Trojanowski J.Q., Lee V.M. Exogenous α-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc. Natl. Acad. Sci. USA 2009, 106:20051-20056.
23. Luk K.C., Kehm V., Carroll J., Zhang B., O'Brien P., Trojanowski J.Q., Lee V.M. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 2012, 338:949-953.
24. Luk K.C., Kehm V.M., Zhang B., O'Brien P., Trojanowski J.Q., Lee V.M. Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodegenerative α-synucleinopathy in mice. J.Exp. Med. 2012, 209:975-986.
25. Masliah E., Rockenstein E., Adame A., Alford M., Crews L., Hashimoto M., Seubert P., Lee M., Goldstein J., Chilcote T., et al. Effects of α-synuclein immunization in a mouse model of Parkinson's disease. Neuron 2005, 46:857-868.
26. Masliah E., Rockenstein E., Mante M., Crews L., Spencer B., Adame A., Patrick C., Trejo M., Ubhi K., Rohn T.T., et al. Passive immunization reduces behavioral and neuropathological deficits in an α-synuclein transgenic model of Lewy body disease. PLoS ONE 2011, 6:e19338.
27. Prusiner S.B. Cell biology. A unifying role for prions in neurodegenerative diseases. Science 2012, 336:1511-1513.
28. Sampathu D.M., Giasson B.I., Pawlyk A.C., Trojanowski J.Q., Lee V.M. Ubiquitination of alpha-synuclein is not required for formation of pathological inclusions in alpha-synucleinopathies. Am. J. Pathol. 2003, 163:91-100.
29. Taylor A.M., Blurton-Jones M., Rhee S.W., Cribbs D.H., Cotman C.W., Jeon N.L. A microfluidic culture platform for CNS axonal injury, regeneration and transport. Nat. Methods 2005, 2:599-605.
30. Volpicelli-Daley L.A., Luk K.C., Patel T.P., Tanik S.A., Riddle D.M., Stieber A., Meaney D.F., Trojanowski J.Q., Lee V.M. Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 2011, 72:57-71.
31. Walker L.C., Jucker M. Seeds of dementia. Sci. Am. 2013, 308:52-57.
32. Wang W., Wang E.Q., Balthasar J.P. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin. Pharmacol. Ther. 2008, 84:548-558.
33. Waxman E.A., Giasson B.I. Specificity and regulation of casein kinase-mediated phosphorylation of α-synuclein. J.Neuropathol. Exp. Neurol. 2008, 67:402-416.
34. Wolfgang W.J., Miller T.W., Webster J.M., Huston J.S., Thompson L.M., Marsh J.L., Messer A. Suppression of Huntington's disease pathology in Drosophila by human single-chain Fv antibodies. Proc. Natl. Acad. Sci. USA 2005, 102:11563-11568.
35. Yanamandra K., Kfoury N., Jiang H., Mahan T.E., Ma S., Maloney S.E., Wozniak D.F., Diamond M.I., Holtzman D.M. Anti-tau antibodies that block tau aggregate seeding invitro markedly decrease pathology and improve cognition invivo. Neuron 2013, 80:402-414.