Monoclonal antibodies selective for α-synuclein oligomers/ protofibrils recognize brain pathology in Lewy body disorders and α-synuclein transgenic mice with the disease-causing A30P mutation

Journal of Neurochemistry

Volumn 126, Issue 1, 2013, Pages 131-144

  Fagerqvist, Therese ^a   Lindström, Veronica ^a   Nordström, Eva ^b   Lord, Anna ^b   Tucker, Stina M E ^b   Su, Xingjian ^a   Sahlin, Charlotte ^b   Kasrayan, Alex ^b   Andersson, Jessica ^b   Welander, Hedvig ^a   Näsström, Thomas ^a   Holmquist, Mats ^b   Schell, Heinrich ^c   Kahle, Philipp J ^c   Kalimo, Hannu ^d   Möller, Christer ^b   Gellerfors, Pär ^b   Lannfelt, Lars ^a   Bergström, Joakim ^a   Ingelsson, Martin ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b BioArctic Neuroscience   (Sweden)

^c GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^d UNIVERSITY OF HELSINKI   (Finland)

Author keywords

alpha synuclein; dementia with Lewy bodies; monoclonal antibody; oligomer; Parkinson's disease; protofibril

Indexed keywords

ALPHA SYNUCLEIN; AMYLOID BETA PROTEIN; BRAIN EXTRACT; EPITOPE; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 38E2; MONOCLONAL ANTIBODY 38F; OLIGOMER; TAU PROTEIN; UNCLASSIFIED DRUG;

AGE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY AFFINITY; ANTIGEN BINDING; ARTICLE; BEHAVIOR DISORDER; CLINICAL ARTICLE; CONTROLLED STUDY; DIFFUSE LEWY BODY DISEASE; ENDOPLASMIC RETICULUM; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE MUTATION; HUMAN; HUMAN TISSUE; MOUSE; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; TRANSGENIC MOUSE;

ALPHA-SYNUCLEIN; ANIMALS; ANTIBODIES, MONOCLONAL; BLOTTING, WESTERN; BRAIN; DNA, COMPLEMENTARY; ENZYME-LINKED IMMUNOSORBENT ASSAY; EPITOPES; FORMATES; HUMANS; IMMUNOHISTOCHEMISTRY; LEWY BODY DISEASE; MICE; MICE, TRANSGENIC; MUTATION; SUBCELLULAR FRACTIONS;

MUS; MUS MUSCULUS;

EID: 84879419913     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.12175     Document Type: Article

References (51)

1. Bae E. J., Lee H. J., Rockenstein E., Ho D. H., Park E. B., Yang N. Y., Desplats P., Masliah E., and, Lee S. J., (2012) Antibody-Aided Clearance of Extracellular alpha-Synuclein Prevents Cell-to-Cell Aggregate Transmission. J. Neurosci. 32, 13454-13469.
2. Bartels T., Choi J. G., and, Selkoe D. J., (2011) alpha-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477, 107-110.
3. Beal M. F., (2010) Parkinson's disease: a model dilemma. Nature 466, S8-S10.
4. Burre J., Sharma M., Tsetsenis T., Buchman V., Etherton M. R., and, Sudhof T. C., (2010) Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329, 1663-1667.
5. Campbell B. C., Li Q. X., Culvenor J. G., Jakala P., Cappai R., Beyreuther K., Masters C. L., and, McLean C. A., (2000) Accumulation of insoluble alpha-synuclein in dementia with Lewy bodies. Neurobiol. Dis. 7, 192-200.
6. Cappai R., Leck S. L., Tew D. J., et al,. (2005) Dopamine promotes alpha-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway. FASEB J. 19, 1377-1379.
7. Cole N. B., Murphy D. D., Lebowitz J., Di Noto L., Levine R. L., and, Nussbaum R. L., (2005) Metal-catalyzed oxidation of alpha-synuclein: helping to define the relationship between oligomers, protofibrils, and filaments. J. Biol. Chem. 280, 9678-9690.
8. Colla E., Jensen P. H., Pletnikova O., Troncoso J. C., Glabe C., and, Lee M. K., (2012a) Accumulation of toxic alpha-synuclein oligomer within endoplasmic reticulum occurs in alpha-synucleinopathy in vivo. J. Neurosci. 32, 3301-3305.
9. Colla E., Coune P., Liu Y., Pletnikova O., Troncoso J. C., Iwatsubo T., Schneider B. L., and, Lee M. K.,. (2012b). " Endoplasmic reticulum stress is important for the manifestations of alpha-synucleinopathy in vivo." J. Neurosci. 32, 3306-3320.
10. Conway K. A., Lee S. J., Rochet J. C., Ding T. T., Williamson R. E., and, Lansbury P. T., Jr, (2000) Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc. Natl. Acad. Sci. USA 97, 571-576.
11. Cox B., and, Emili A.,. (2006). Tissue subcellular fractionation and protein extraction for use in mass-spectrometry-based proteomics. Nat. Protoc. 4, 1872-1878
12. Danzer K. M., Haasen D., Karow A. R., Moussaud S., Habeck M., Giese A., Kretzschmar H., Hengerer B., and, Kostka M., (2007) Different species of alpha-synuclein oligomers induce calcium influx and seeding. J. Neurosci. 27, 9220-9232.
13. Del Tredici K., and, Braak H., (2012) Spinal cord lesions in sporadic Parkinson's disease. Acta Neuropathol. 124, 643-664.
14. Diogenes M. J., Dias R. B., Rombo D. M., et al,. (2012) Extracellular alpha-synuclein oligomers modulate synaptic transmission and impair LTP via NMDA-receptor activation. J. Neurosci. 32, 11750-11762.
15. Ehrnhoefer D. E., Bieschke J., Boeddrich A., Herbst M., Masino L., Lurz R., Engemann S., Pastore A., and, Wanker E. E., (2008) EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat. Struct. Mol. Biol. 15, 558-566.
16. Emadi S., Barkhordarian H., Wang M. S., Schulz P., and, Sierks M. R., (2007) Isolation of a human single chain antibody fragment against oligomeric alpha-synuclein that inhibits aggregation and prevents alpha-synuclein-induced toxicity. J. Mol. Biol. 368, 1132-1144.
17. Englund H., Sehlin D., Johansson A. S., Nilsson L. N., Gellerfors P., Paulie S., Lannfelt L., and, Pettersson F. E., (2007) Sensitive ELISA detection of amyloid-beta protofibrils in biological samples. J. Neurochem. 103, 334-345.
18. Fauvet B., Mbefo M. K., Fares M. B., et al,. (2012). Alpha-synuclein in the central nervous system and from erythrocytes, mammalian cells and E. coli exists predominantly as a disordered monomer. J. Biol. Chem. 19, 15345-15364.
19. Freichel C., Neumann M., Ballard T., et al,. (2007) Age-dependent cognitive decline and amygdala pathology in alpha-synuclein transgenic mice. Neurobiol. Aging 28, 1421-1435.
20. Harding A. J., and, Halliday G. M., (2001) Cortical Lewy body pathology in the diagnosis of dementia. Acta Neuropathol. 102, 355-363.
21. Kahle P. J., Neumann M., Ozmen L., et al,. (2000) Subcellular localization of wild-type and Parkinson's disease-associated mutant alpha -synuclein in human and transgenic mouse brain. J. Neurosci. 20, 6365-6373.
22. Kahle P. J., Neumann M., Ozmen L., et al,. (2001) Selective insolubility of alpha-synuclein in human Lewy body diseases is recapitulated in a transgenic mouse model. Am. J. Pathol. 159, 2215-2225.
23. Kayed R., Canto I., Breydo L., et al,. (2010) Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Abeta oligomers. Mol. Neurodegener. 5, 57.
24. Klucken J., Ingelsson M., Shin Y., Irizarry M. C., Hedley-Whyte E. T., Frosch M., Growdon J., McLean P., and, Hyman B. T., (2006) Clinical and biochemical correlates of insoluble alpha-synuclein in dementia with Lewy bodies. Acta Neuropathol. 111, 101-108.
25. Konno T., Morii T., Hirata A., Sato S., Oiki S., and, Ikura K., (2005) Covalent blocking of fibril formation and aggregation of intracellular amyloidgenic proteins by transglutaminase-catalyzed intramolecular cross-linking. Biochemistry 44, 2072-2079.
26. Leverenz J. B., Umar I., Wang Q., et al,. (2007) Proteomic identification of novel proteins in cortical lewy bodies. Brain Pathol. 17, 139-145.
27. Martin Z. S., Neugebauer V., Dineley K. T., Kayed R., Zhang W., Reese L. C., and, Taglialatela G., (2012) alpha-Synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases. J. Neurochem. 120, 440-452.
28. Masliah E., Rockenstein E., Mante M., et al,. (2011) Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease. PLoS ONE 6, e19338.
29. Mollenhauer B., Cullen V., Kahn I., et al,. (2008) Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp. Neurol. 213, 315-325.
30. Nasstrom T., Wahlberg T., Karlsson M., Nikolajeff F., Lannfelt L., Ingelsson M., and, Bergstrom J., (2009) The lipid peroxidation metabolite 4-oxo-2-nonenal cross-links alpha-synuclein causing rapid formation of stable oligomers. Biochem. Biophys. Res. Commun. 378, 872-876.
31. Nasstrom T., Fagerqvist T., Barbu M., Karlsson M., Nikolajeff F., Kasrayan A., Ekberg M., Lannfelt L., Ingelsson M., and, Bergstrom J., (2011) The lipid peroxidation products 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote the formation of alpha-synuclein oligomers with distinct biochemical, morphological, and functional properties. Free Radic. Biol. Med. 50, 428-437.
32. Nemani V. M., Lu W., Berge V., Nakamura K., Onoa B., Lee M. K., Chaudhry F. A., Nicoll R. A., and, Edwards R. H., (2010) Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65, 66-79.
33. Neri D., Montigiani S., and, Kirkham P. M., (1996) Biophysical methods for the determination of antibody-antigen affinities. Trends Biotechnol. 14, 465-470.
34. Neumann M., Kahle P. J., Giasson B. I., et al,. (2002) Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. J. Clin. Invest. 110, 1429-1439.
35. Oinas M., Paetau A., Myllykangas L., Notkola I. L., Kalimo H., and, Polvikoski T., (2010) alpha-Synuclein pathology in the spinal cord autonomic nuclei associates with alpha-synuclein pathology in the brain: a population-based Vantaa 85+ study. Acta Neuropathol. 119, 715-722.
36. Paleologou K. E., Kragh C. L., Mann D. M., Salem S. A., Al-Shami R., Allsop D., Hassan A. H., Jensen P. H., and, El-Agnaf O. M., (2009) Detection of elevated levels of soluble alpha-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies. Brain 132, 1093-1101.
37. Parnetti L., Chiasserini D., Bellomo G., et al,. (2011) Cerebrospinal fluid Tau/alpha-synuclein ratio in Parkinson's disease and degenerative dementias. Mov. Disord. 26, 1428-1435.
38. Roy S., (2009) The paradoxical cell biology of alpha-Synucle. Results Probl. Cell Differ. 48, 159-172.
39. Schell H., Hasegawa T., Neumann M., and, Kahle P. J., (2009) Nuclear and neuritic distribution of serine-129 phosphorylated alpha-synuclein in transgenic mice. Neuroscience 160, 796-804.
40. Sharon R., Bar-Joseph I., Frosch M. P., Walsh D. M., Hamilton J. A., and, Selkoe D. J., (2003) The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron 37, 583-595.
41. Souza J. M., Giasson B. I., Chen Q., Lee V. M., and, Ischiropoulos H., (2000) Dityrosine cross-linking promotes formation of stable alpha -synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies. J. Biol. Chem. 275, 18344-18349.
42. de StGroth S. F., and, Scheidegger D., (1980) Production of monoclonal antibodies: strategy and tactics. J. Immunol. Methods 35, 1-21.
43. Tokuda T., Salem S. A., Allsop D., Mizuno T., Nakagawa M., Qureshi M. M., Locascio J. J., Schlossmacher M. G., and, El-Agnaf O. M., (2006) Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease. Biochem. Biophys. Res. Commun. 349, 162-166.
44. Tokuda T., Qureshi M. M., Ardah M. T., Varghese S., Shehab S. A., Kasai T., Ishigami N., Tamaoka A., Nakagawa M., and, El-Agnaf O. M.,. (2010). Detection of elevated levels of {alpha}-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 20, 1766-1772.
45. Uversky V. N., Li J., and, Fink A. L., (2001) Evidence for a partially folded intermediate in alpha-synuclein fibril formation. J. Biol. Chem. 276, 10737-10744.
46. Volles M. J., Lee S. J., Rochet J. C., Shtilerman M. D., Ding T. T., Kessler J. C., and, Lansbury P. T., Jr, (2001) Vesicle permeabilization by protofibrillar alpha-synuclein: implications for the pathogenesis and treatment of Parkinson's disease. Biochemistry 40, 7812-7819.
47. Wakabayashi K., Mori F., Tanji K., Orimo S., and, Takahashi H., (2010) Involvement of the peripheral nervous system in synucleinopathies, tauopathies and other neurodegenerative proteinopathies of the brain. Acta Neuropathol. 120, 1-12.
48. Wilms H., Rosenstiel P., Romero-Ramos M., et al,. (2009) Suppression of MAP kinases inhibits microglial activation and attenuates neuronal cell death induced by alpha-synuclein protofibrils. Int. J. Immunopathol. Pharmacol. 22, 897-909.
49. Winner B., Jappelli R., Maji S. K., et al,. (2011) In vivo demonstration that alpha-synuclein oligomers are toxic. Proc. Natl. Acad. Sci. USA 108, 4194-4199.
50. Yoritaka A., Hattori N., Uchida K., Tanaka M., Stadtman E. R., and, Mizuno Y., (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc. Natl Acad. Sci. USA 93, 2696-2701.
51. Zhu M., Rajamani S., Kaylor J., Han S., Zhou F., and, Fink A. L., (2004) The flavonoid baicalein inhibits fibrillation of alpha-synuclein and disaggregates existing fibrils. J. Biol. Chem. 279, 26846-26857. Research