α-Synuclein structural features inhibit harmful polyunsaturated fatty acid oxidation, suggesting roles in neuroprotection

Journal of Biological Chemistry

Volumn 292, Issue 17, 2017, Pages 6927-6937

  De Franceschi, Giorgia ^a   Fecchio, Chiara ^a   Sharon, Ronit ^b   Schapira, Anthony H V ^c   Proukakis, Christos ^c   Bellotti, Vittorio ^d,e   De Laureto, Patrizia Polverino ^a  

^a UNIVERSITY OF PADOVA   (Italy)

^b HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

^e UNIVERSITY OF PAVIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ABILITY TESTING; AMINO ACIDS; BRAIN; MASS SPECTROMETRY; NEURODEGENERATIVE DISEASES;

CHEMICALLY MODIFIED; COVALENT MODIFICATIONS; DOCOSAHEXAENOIC ACID; NEURODEGENERATIVE DISORDERS; PROTECTIVE FUNCTION; SCAVENGING ACTIVITIES; SECONDARY STRUCTURES; SPECTROSCOPIC TECHNIQUE;

POLYUNSATURATED FATTY ACIDS;

ALPHA SYNUCLEIN; DOCOSAHEXAENOIC ACID; POLYUNSATURATED FATTY ACID; ARACHIDONIC ACID; LYSINE; METHIONINE; OXYGEN; TRYPSIN; UNSATURATED FATTY ACID;

ACIDIFICATION; AMINO ACID SEQUENCE; ANTIOXIDANT ACTIVITY; ARTICLE; AUTOOXIDATION; CHEMICAL MODIFICATION; CIRCULAR DICHROISM; CONTROLLED STUDY; ELECTROSPRAY; LIPID HOMEOSTASIS; LIPID OXIDATION; MASS SPECTROMETRY; MOLECULAR WEIGHT; NEUROPROTECTION; PARKINSON DISEASE; POLARIMETER; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN LIPID INTERACTION; PROTEIN PURIFICATION; SPECTROPHOTOMETRY; STRUCTURE ANALYSIS; BINDING SITE; BRAIN; CHEMISTRY; HUMAN; LIPID METABOLISM; METABOLISM; PROTEIN SECONDARY STRUCTURE;

ALPHA-SYNUCLEIN; ARACHIDONIC ACID; BINDING SITES; BRAIN; CIRCULAR DICHROISM; DOCOSAHEXAENOIC ACIDS; FATTY ACIDS, UNSATURATED; HUMANS; LIPID METABOLISM; LYSINE; MASS SPECTROMETRY; METHIONINE; NEUROPROTECTION; OXYGEN; PARKINSON DISEASE; PROTEIN STRUCTURE, SECONDARY; TRYPSIN;

EID: 85018335432     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M116.765149     Document Type: Article

References (63)

1. Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., and Goedert, M. (1998) α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. U.S.A. 95, 6469-6473
2. Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E. S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W. G., et al. (1997) Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276, 2045-2047
3. Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schöls, L., and Riess, O. (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat. Genet. 18, 106-108
4. Zarranz, J. J., Alegre, J., Gómez-Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., Vidal, L., Hoenicka, J., Rodriguez, O., Atarés, B., Llorens, V., Gomez Tortosa, E., del Ser, T., Muñoz, D. G., and de Yebenes, J. G. (2004) The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55, 164-173
5. Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., Lincoln, S., Crawley, A., Hanson, M., Maraganore, D., Adler, D. C., et al. (2003) α-Synuclein locus triplication causes Parkinson's disease. Science 302, 841
6. Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A., and Lansbury, P. T., Jr. (1996) NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. Biochemistry 35, 13709-13715
7. Davidson, W. S., Jonas, A., Clayton, D. F., and George, J. M. (1998) Stabilization of α-synuclein secondary structure upon binding to synthetic membranes. J. Biol. Chem. 273, 9443-9449
8. Jo, E., McLaurin, J., Yip, C. M., St George-Hyslop, P., and Fraser, P. E. (2000) α-Synuclein membrane interactions and lipid specificity. J. Biol. Chem. 275, 34328-34334
9. Uéda, K., Fukushima, H., Masliah, E., Xia, Y., Iwai, A., Yoshimoto, M., Otero, D. A., Kondo, J., Ihara, Y., and Saitoh, T. (1993) Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A. 90, 11282-11286
10. Snead, D., and Eliezer, D. (2014) α-Synuclein function and dysfunction on cellular membrane. Exp. Neurobiol. 23, 292-313
11. Jiang, Z., de Messieres, M., and Lee, J. C. (2013) Membrane remodeling by α-synuclein and effects on amyloid formation. J. Am. Chem. Soc. 135, 15970-15973
12. Ouberai, M. M., Wang, J., Swann, M. J., Galvagnion, C., Guilliams, T., Dobson, C. M., and Welland, M. E. (2013) α-Synuclein senses lipid packing defects and induces lateral expansion of lipids leading to membrane remodeling. J. Biol. Chem. 288, 20883-20895
13. Burré, J., Sharma, M., Tsetsenis, T., Buchman, V., Etherton, M. R., and Südhof, T. C. (2010) α-Synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329, 1663-1667
14. Burré, J., Sharma, M., and Südhof, T. C. (2014) α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation. Proc. Natl. Acad. Sci. U.S.A. 111, E4274-4283
15. Ruipérez, V., Darios, F., and Davletov, B. (2010) α-Synuclein, lipids and Parkinson's disease. Prog. Lipid Res. 49, 420-428
16. Niki, E., Yoshida, Y., Saito, Y., and Noguchi, N. (2005) Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochem. Biophys. Res. Commun. 338, 668-676
17. Yin, H., Xu, L., and Porter, N. A. (2011) Free radical lipid peroxidation: mechanisms and analysis. Chem. Rev. 111, 5944-5972
18. Derogis, P. B., Freitas, F. P., Marques, A. S., Cunha, D., Appolinário, P. P., de Paula, F., Lourenço, T. C., Murgu, M., Di Mascio, P., Medeiros, M. H., and Miyamoto, S. (2013) The development of a specific and sensitive LC-MS-based method for the detection and quantification of hydroperoxy-and hydroxydocosahexaenoic acids as a tool for lipidomic analysis. PLoS ONE 8, e77561
19. Frankel, E. N. (1984) Chemistry of free radical and singlet oxidation of lipids. Prog. Lipid Res. 23, 197-221
20. Reed, T. T. (2011) Lipid peroxidationand neurodegenerative disease. Free Radic. Biol. Med. 51, 1302-1319
21. Tsang, A. H., and Chung, K. K. (2009) Oxidative and nitrosative stress in Parkinson's disease. Biochim. Biophys. Acta 1792, 643-650
22. Pérez-De La Cruz, V., Elinos-Calderón, D., Robledo-Arratia, Y., Medina-Campos, O. N., Pedraza-Chaverrí, J., Ali, S. F., and Santamaría, A. (2009) Targeting oxidative/nitrergic stress ameliorates motor impairment, and attenuates synaptic mitochondrial dysfunction and lipid peroxidation in two models of Huntington's disease. Behav. Brain Res. 199, 210-217
23. Galasko, D., and Montine, T. J. (2010) Biomarkers of oxidative damage and inflammation in Alzheimer's disease. Biomark. Med. 4, 27-36
24. Dalfó, E., Portero-Otín, M., Ayala, V., Martínez, A., Pamplona, R., and Ferrer, I. (2005) Evidence of oxidative stress in the neocortex in incidental Lewy body disease. J. Neuropathol. Exp. Neurol. 64, 816-830
25. Morel, P., Tallineau, C., Pontcharraud, R., Piriou, A., and Huguet, F. (1998) Effects of 4-hydroxynonenal, a lipid peroxidation product, on dopamine transport and Na+/K+ ATPase in rat striatal synaptosomes. Neurochem. Int. 33, 531-540
26. Broersen, K., van den Brink, D., Fraser, G., Goedert, M., and Davletov, B. (2006) α-Synuclein adopts an α-helical conformation in the presence of polyunsaturated fatty acids to hinder micelle formation. Biochemistry 45, 15610-15616
27. De Franceschi, G., Frare, E., Bubacco, L., Mammi, S., Fontana, A., and de Laureto, P. P. (2009) Molecular insights into the interaction between α-synuclein and docosahexaenoic acid. J. Mol. Biol. 394, 94-107
28. Fecchio, C., De Franceschi, G., Relini, A., Greggio, E., Dalla Serra, M., Bubacco, L., and Polverino de Laureto, P. (2013) α-Synuclein oligomers induced by docosahexaenoic acid affect membrane integrity. PLoS ONE 8, e82732
29. De Franceschi, G., Frare, E., Pivato, M., Relini, A., Penco, A., Greggio, E., Bubacco, L., Fontana, A., and de Laureto, P. P. (2011) Structural and morphological characterization of aggregated species of α-synuclein induced by docosahexaenoic acid. J. Biol. Chem. 286, 22262-22274
30. Glaser, C. B., Yamin, G., Uversky, V. N., and Fink, A. L. (2005) Methionine oxidation, α-synuclein and Parkinson's disease. Biochim. Biophys. Acta 1703, 157-169
31. Maltsev, A. S., Chen, J., Levine, R. L., and Bax, A. (2013) Site-specific interaction between α-synuclein and membranes probed by NMR-observed methionine oxidation rates. J. Am. Chem. Soc. 135, 2943-2946
32. Bae, E. J., Ho, D. H., Park, E., Jung, J. W., Cho, K., Hong, J. H., Lee, H. J., Kim, K. P., and Lee, S. J. (2013) Lipid peroxidation product 4-hydroxy-2-nonenal promotes seeding-capable oligomer formation and cell-to-cell transfer of α-synuclein. Antioxid. Redox Signal. 18, 770-783
33. Schildknecht, S., Gerding, H. R., Karreman, C., Drescher, M., Lashuel, H. A., Outeiro, T. F., Di Monte, D. A., and Leist, M. (2013) Oxidative and nitrative α-synuclein modifications and proteostatic stress: implications for disease mechanisms and interventions in synucleinopathies. J. Neurochem. 125, 491-511
34. Proukakis, C., Dudzik, C. G., Brier, T., MacKay, D. S., Cooper, J. M., Millhauser, G. L., Houlden, H., and Schapira, A. H. (2013) A novel aS missense mutation in Parkinson disease. Neurology 80, 1062-1064
35. Porcari, R., Proukakis, C., Waudby, C. A., Bolognesi, B., Mangione, P. P., Paton, J. F., Mullin, S., Cabrita, L. D., Penco, A., Relini, A., Verona, G., Vendruscolo, M., Stoppini, M., Tartaglia, G. G., Camilloni, C., et al. (2014) The H50Q mutation induces a 10-fold decrease in the solubility of α-synuclein. J. Biol. Chem. 290, 2395-2404
36. Appel-Cresswell, S., Vilarino-Guell, C., Encarnacion, M., Sherman, H., Yu, I., Shah, B., Weir, D., Thompson, C., Szu-Tu, C., Trinh, J., Aasly, J. O., Rajput, A., Rajput, A. H., Jon Stoessl, A., and Farrer, M. J. (2013) α-Synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease. Mov. Disord. 28, 811-813
37. Murphy, R. C., and Axelsen, P. H. (2011) Mass spectrometric analysis of long-chain lipids. Mass Spectrom. Rev. 30, 579-599
38. Xiang, W., Menges, S., Schlachetzki, J. C., Meixner, H., Hoffmann, A. C., Schlötzer-Schrehardt, U., Becker, C.-M., Winkler, J., and Klucken, J. (2015) Posttranslational modification and mutation of histidine 50 trigger α-synuclein aggregation and toxicity. Mol. Neurodegener. 10, 8-24
39. Chavarría, C., and Souza, J. M. (2013) Oxidation and nitration of α-synuclein and their implications in neurodegenerative diseases. Arch. Biochem. Biophys. 533, 25-32
40. Subczynski, W. K., and Hyde, J. S. (1983) Concentration of oxygen in lipid bilayers using a spin-label method. Biophys. J. 41, 283-286
41. Esterbauer, H., Schaur, R. J., and Zollner, H. (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic. Biol. Med. 11, 81-128
42. Uchida, K. (2003) Histidine and lysine as targets of oxidative modification. Amino Acids 25, 249-257
43. Trostchansky, A., Lind, S., Hodara, R., Oe, T., Blair, I. A., Ischiropoulos, H., Rubbo, H., and Souza, J. M. (2006) Interaction with phospholipids modulates α-synuclein nitration and lipid-protein adduct formation. Biochem. J. 393, 343-349
44. Zhu, M., Qin, Z. J., Hu, D., Munishkina, L. A., and Fink, A. L. (2006) α-Synuclein can function as an antioxidant preventing oxidation of unsaturated lipid in vesicles. Biochemistry 45, 8135-8142
45. Liu, F., Hindupur, J., Nguyen, J. L., Ruf, K. J., Zhu, J., Schieler, J. L., Bonham, C. C., Wood, K. V., Davisson, V. J., and Rochet, J. C. (2008) Methionine sulfoxide reductase A protects dopaminergic cells from Parkinson's disease-related insults. Free Radic. Biol. Med. 45, 242-255
46. Khalaf, O., Fauvet, B., Oueslati, A., Dikiy, I., Mahul-Mellier, A. L., Ruggeri, F. S., Mbefo, M. K., Vercruysse, F., Dietler, G., Lee, S. J., Eliezer, D., and Lashuel, H. A. (2014) The H50Q mutation enhances α-synuclein aggregation, secretion, and toxicity. J. Biol. Chem. 289, 21856-21876
47. Vilar, M., Chou, H. T., Lührs, T., Maji, S. K., Riek-Loher, D., Verel, R., Manning, G., Stahlberg, H., and Riek, R. (2008) The fold of α-synuclein fibrils. Proc. Natl. Acad. Sci. U.S.A. 105, 8637-8642
48. Comellas, G., Lemkau, L. R., Nieuwkoop, A. J., Kloepper, K. D., Ladror, D. T., Ebisu, R., Woods, W. S., Lipton, A. S., George, J. M., and Rienstra, C. M. (2011) Structured regions of α-synuclein fibrils include the earlyonset Parkinson's disease mutation sites. J. Mol. Biol. 411, 881-895
49. Zarbiv, Y., Simhi-Haham, D., Israeli, E., Elhadi, S. A., Grigoletto, J., and Sharon, R. (2014) Lysine residues at the first and second KTKEGV repeats mediate α-Synuclein binding to membrane phospholipids. Neurobiol. Dis. 70, 90-98
50. Bartels, T., Ahlstrom, L. S., Leftin, A., Kamp, F., Haass, C., Brown, M. F., and Beyer, K. (2010) The N-terminus of the intrinsically disordered protein α-synuclein triggers membrane binding and helix folding. Biophys. J. 99, 2116-2124
51. Fusco, G., De Simone, A., Gopinath, T., Vostrikov, V., Vendruscolo, M., Dobson, C. M., and Veglia, G. (2014) Direct observation of the three regions in α-synuclein that determine its membrane-bound behaviour. Nat. Commun. 5, 3827
52. Stefanis, L. (2012) α-Synuclein in Parkinson's disease. Cold Spring Harb. Perspect. Med. 2, a009399
53. De Franceschi, G., and Polverino de Laureto, P. (2014) Role of different regions of α-synuclein in the interaction with the brain fatty acid DHA. J. Chromatograph. Separat. Techniq. 5, 219-226
54. Miyashita, K. (2014) Paradox of omega-3 PUFA oxidation. Eur. J. Lipid Sci. Technol. 116, 1268-1279
55. Sharon, R., Bar-Joseph, I., Mirick, G. E., Serhan, C. N., and Selkoe, D. J. (2003) Altered fatty acid composition of dopaminergic neurons expressing α-synuclein and human brains with α-synucleinopathies. J. Biol. Chem. 278, 49874-49881
56. Assayag, K., Yakunin, E., Loeb, V., Selkoe, D. J., and Sharon, R. (2007) Polyunsaturated fatty acids induce α-synuclein-related pathogenic changes in neuronal cells. Am. J. Pathol. 171, 2000-2011
57. Leong, S. L., Pham, C. L., Galatis, D., Fodero-Tavoletti, M. T., Perez, K., Hill, A. F., Masters, C. L., Ali, F. E., Barnham, K. J., and Cappai, R. (2009) Formation of dopamine-mediated α-synuclein-soluble oligomers requires methionine oxidation. Free Radic. Biol. Med. 46, 1328-1337
58. Binolfi, A., Limatola, A., Verzini, S., Kosten, J., Theillet, F.-X., Rose, H. M., Bekei, B., Stuiver, M., van Rossum, M., and Selenko, P. (2016) Intracellular repair of oxidation-damaged α-synuclein fails to target C-terminal modification sites. Nat. Commun. 7, 10251
59. Lukiw, W. J., and Bazan, N. G. (2008) Docosahexaenoic acid and the aging brain. J. Nutr. 138, 2510-2514
60. Darios, F., Ruipérez, V., López, I., Villanueva, J., Gutierrez, L. M., and Davletov, B. (2010) α-Synuclein sequesters arachidonic acid to modulate SNARE-mediated exocytosis. EMBO Rep. 11, 528-533
61. Gill, S. C., and von Hippel, P. H. (1989) Calculation of protein extinction coefficients from amino acids sequence data. Anal. Biochem. 182, 319-326
62. Uversky, V. N., Yamin, G., Souillac, P. O., Goers, J., Glaser, C. B., and Fink, A. L. (2002) Methionine oxidation inhibits fibrillation of human α-synuclein in vitro. FEBS Lett. 517, 239-244
63. Means, G. E., and Feeney, R. E. (1971) Chemical Modification of Proteins, Vol. 2, Holden-Day Inc., San Francisco