Biophysical groundwork as a hinge to unravel the biology of α-synuclein aggregation and toxicity

Quarterly Reviews of Biophysics

Volumn 47, Issue 1, 2014, Pages 1-48

  Plotegher, Nicoletta ^a   Greggio, Elisa ^a   Bisaglia, Marco ^a   Bubacco, Luigi ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN;

AMINO ACID SEQUENCE; ANIMAL; BIOPHYSICS; CELLS; CHEMISTRY; HUMAN; KINETICS; METABOLISM; MOLECULAR GENETICS; PROCEDURES; PROTEIN MULTIMERIZATION; PROTEIN SECONDARY STRUCTURE;

ALPHA-SYNUCLEIN; AMINO ACID SEQUENCE; ANIMALS; BIOPHYSICS; CELLS; HUMANS; KINETICS; MOLECULAR SEQUENCE DATA; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, SECONDARY;

EID: 84898665782     PISSN: 00335835     EISSN: 14698994     Source Type: Journal    
DOI: 10.1017/S0033583513000097     Document Type: Review

References (220)

1. ABELIOVICH, A., SCHMITZ, Y., FARINAS, I., CHOI-LUNDBERG, D., HO, W. H., CASTILLO, P. E., SHINSKY, N., VERDUGO, J. M., ARMANINI, M., RYAN, A., HYNES, M., PHILLIPS, H., SULZER, D. & ROSENTHAL, A. (2000). Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25(1), 239-252.
2. ALIM, M. A., MA, Q. L., TAKEDA, K., AIZAWA, T., MATSUBARA, M., NAKAMURA, M., ASADA, A., SAITO, T., KAJI, H., YOSHII, M., HISANAGA, S. & UEDA, K. (2004). Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein. Journal of Alzheimer's Disease 6(4), 435-442; discussion 443-439.
3. ALLISON, J. R., VARNAI, P., DOBSON, C.M. & VENDRUSCOLO, M. (2009). Determination of the free energy landscape of alpha-synuclein using spin label nuclear magnetic resonance measurements. Journal of American Chemical Socirty 131(51), 18314-18326.
4. ALVAREZ-ERVITI, L., COUCH, Y., RICHARDSON, J., COOPER, J.M. & WOOD, M. J. (2011a). Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line. Neuroscience Research 69(4), 337-342.
5. ALVAREZ-ERVITI, L., SEOW, Y., SCHAPIRA, A. H., GARDINER, C., SARGENT, I. L., WOOD, M.J. & COOPER, J.M. (2011b). Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiology of Disease 42(3), 360-367.
6. ANDERSON, J. P., WALKER, D. E., GOLDSTEIN, J. M., DE LAAT, R., BANDUCCI, K., CACCAVELLO, R. J., BARBOUR, R., HUANG, J., KLING, K., LEE, M., DIEP, L., KEIM, P. S., SHEN, X., CHATAWAY, T., SCHLOSSMACHER, M. G., SEUBERT, P., SCHENK, D., SINHA, S., GAI, W.P. & CHILCOTE, T. J. (2006). Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. Journal of Biological Chemistry 281(40), 29739-29752.
7. APETRI, M. M., MAITI, N. C., ZAGORSKI, M. G., CAREY, P. R. & ANDERSON, V. E. (2006). Secondary structure of alpha-synuclein oligomers: characterization by Raman and atomic force microscopy. Journal of Molecular Biology 355(1), 63-71.
8. AULUCK, P. K., CARAVEO, G. & LINDQUIST, S. (2010). alpha-Synuclein: membrane interactions and toxicity in Parkinson's disease. Annual Review of Cell and Developmental Biology 26, 211-233.
9. AULUCK, P. K., CHAN, H. Y., TROJANOWSKI, J. Q., LEE, V. M. & BONINI, N.M. (2002). Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295(5556), 865-868.
10. BARTELS, T., AHLSTROM, L. S., LEFTIN, A., KAMP, F., HAASS, C., BROWN, M.F. & BEYER, K. (2010). The N-terminus of the intrinsically disordered protein alphasynuclein triggers membrane binding and helix folding. Biophysics Journal 99(7), 2116-2124.
11. BARTELS, T., CHOI, J.G. & SELKOE, D. J. (2011). alpha-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477 (7362), 107-110.
12. BERMAN, S.B. & HASTINGS, T. G. (1999). Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson's disease. Journal of Neurochemistry 73(3), 1127-1137.
13. BERTONCINI, C.W., JUNG, Y. S., FERNANDEZ, C. O., HOYER, W., GRIESINGER, C., JOVIN, T.M. & ZWECKSTETTER, M. (2005). Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein. Proceedings of the National Academy of Sciences United States of America 102(5), 1430-1435.
14. BHAK, G., LEE, J. H., HAHN, J.S. & PAIK, S. R. (2009). Granular assembly of alpha-synuclein leading to the accelerated amyloid fibril formation with shear stress. PLoS ONE 4(1), e4177.
15. BIESCHKE, J., RUSS, J., FRIEDRICH, R. P., EHRNHOEFER, D. E., WOBST, H., NEUGEBAUER, K. & WANKER, E.E. (2010). EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity. Proceedings of the National Academy of Sciences United States of America 107(17), 7710-7715.
16. BINOLFI, A., THEILLET, F.X. & SELENKO, P. (2012). Bacterial in-cell NMR of human alpha-synuclein: a disordered monomer by nature? Biochemical Society Transaction, 40(5), 950-954.
17. BISAGLIA, M., MAMMI, S. & BUBACCO, L. (2007). Kinetic and structural analysis of the early oxidation products of dopamine: analysis of the interactions with alphasynuclein. Journal of Biological Chemistry 282(21), 15597-15605.
18. BISAGLIA, M., TESSARI, I., MAMMI, S. & BUBACCO, L. (2009). Interaction between alpha-synuclein and metal ions, still looking for a role in the pathogenesis of Parkinson's disease. Neuromolecular Medicine 11(4), 239-251.
19. BORBAT, P., RAMLALL, T. F., FREED, J.H. & ELIEZER, D. (2006). Inter-helix distances in lysophospholipid micellebound alpha-synuclein from pulsed ESR measurements. Journal of the American Chemical Society 128(31), 10004-10005.
20. BRAAK, H., DEL TREDICI, K., RUB, U., DE VOS, R. A., JANSEN STEUR, E.N. & BRAAK, E. (2003). Staging of brain pathology related to sporadic Parkinson's disease. Neurobiology of Aging 24(2), 197-211.
21. BROOKS, D. J. (1998). The early diagnosis of Parkinson's disease. Annals of Neurology 44(3 Suppl 1), S10-S18.
22. BRUCALE, M., SANDAL, M., DI MAIO, S., RAMPIONI, A., TESSARI, I., TOSATTO, L., BISAGLIA, M., BUBACCO, L. & SAMORI, B. (2009). Pathogenic mutations shift the equilibria of alpha-synuclein single molecules towards structured conformers. ChemBioChem 10(1), 176-183.
23. BURKE, W. J., KUMAR, V. B., PANDEY, N., PANNETON, W. M., GAN, Q., FRANKO, M.W., O'DELL, M., LI, S.W., PAN, Y., CHUNG, H.D. & GALVIN, J. E. (2008). Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine. Acta Neuropathology 115(2), 193-203.
24. BURRE, J., SHARMA, M., TSETSENIS, T., BUCHMAN, V., ETHERTON, M.R. & SUDHOF, T. C. (2010). Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329(5999), 1663-1667.
25. BUSSELL, R. Jr., RAMLALL, T.F. & ELIEZER, D. (2005). Helix periodicity, topology, and dynamics of membraneassociated alpha-synuclein. Protein Science 14(4), 862-872.
26. BUTTERFIELD, S.M. & LASHUEL, H. A. (2010). Amyloidogenic protein-membrane interactions: mechanistic insight from model systems. Angewandte Chemie International Edition English 49(33), 5628-5654.
27. BUTTNER, S., DELAY, C., FRANSSENS, V., BAMMENS, T., RULI, D., ZAUNSCHIRM, S., DE OLIVEIRA, R. M., OUTEIRO, T. F., MADEO, F., BUEE, L., GALAS, M.C. & WINDERICKX, J. (2010). Synphilin-1 enhances alphasynuclein aggregation in yeast and contributes to cellular stress and cell death in a Sir2-dependent manner. PLoS ONE 5(10), e13700.
28. CAPPAI, R., LECK, S. L., TEW, D. J., WILLIAMSON, N. A., SMITH, D. P., GALATIS, D., SHARPLES, R. A., CURTAIN, C. C., ALI, F. E., CHERNY, R. A., CULVENOR, J. G., BOTTOMLEY, S. P., MASTERS, C. L., BARNHAM, K. J. & HILL, A. F. (2005). Dopamine promotes alpha-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway. FASEB Journal 19(10), 1377-1379.
29. CASUSO, I., RICO, F. & SCHEURING, S. (2011). Biological AFM: where we come from-where we are-where we may go. Journal of Molecular Recognition 24(3), 406-413.
30. CHARTIER-HARLIN, M. C., KACHERGUS, J., ROUMIER, C., MOUROUX, V., DOUAY, X., LINCOLN, S., LEVECQUE, C., LARVOR, L., ANDRIEUX, J., HULIHAN, M., WAUCQUIER, N., DEFEBVRE, L., AMOUYEL, P., FARRER, M. & DESTEE, A. (2004). Alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364(9440), 1167-1169.
31. CHEN, M., MARGITTAI, M., CHEN, J. & LANGEN, R. (2007). Investigation of alpha-synuclein fibril structure by sitedirected spin labeling. Journal of Biological Chemistry 282 (34), 24970-24979.
32. CHO, M. K., NODET, G., KIM, H. Y., JENSEN, M. R., BERNADO, P., FERNANDEZ, C. O., BECKER, S., BLACKLEDGE, M. & ZWECKSTETTER, M. (2009). Structural characterization of alpha-synuclein in an aggregation prone state. Protein Science 18(9), 1840-1846.
33. CHOI, B. K., CHOI, M. G., KIM, J. Y., YANG, Y., LAI, Y., KWEON, D. H., LEE, N.K. & SHIN, Y. K. (2013). Large alpha-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking. Proceedings of the National Academy of Sciences United States of America 110 (10), 4087-4092.
34. CLAYTON, D.F. & GEORGE, J.M. (1998). The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends in Neuroscience 21(6), 249-254.
35. CLAYTON, D.F. & GEORGE, J.M. (1999). Synucleins in synaptic plasticity and neurodegenerative disorders. Journal of Neuroscience Research 58(1), 120-129.
36. CODOLO, G., PLOTEGHER, N., POZZOBON, T., BRUCALE, M., TESSARI, I., BUBACCO, L. & DE BERNARD, M. (2013). Triggering of inflammasome by aggregated alphasynuclein, an inflammatory response in synucleinopathies. PLoS ONE 8(1), e55375.
37. COHLBERG, J. A., LI, J., UVERSKY, V.N. & FINK, A.L. (2002). Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from alpha-synuclein in vitro. Biochemistry 41(5), 1502-1511.
38. COLLA, E., JENSEN, P. H., PLETNIKOVA, O., TRONCOSO, J. C., GLABE, C. & LEE, M. K. (2012). Accumulation of toxic alpha-synuclein oligomer within endoplasmic reticulum occurs in alpha-synucleinopathy in vivo. Journal of Neuroscience 32(10), 3301-3305.
39. 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. & RIENSTRA, C.M. (2011). Structured regions of alphasynuclein fibrils include the early-onset Parkinson's disease mutation sites. Journal of Molecular Biology 411(4), 881-895.
40. COMELLAS, G., LEMKAU, L. R., ZHOU, D. H., GEORGE, J.M. & RIENSTRA, C.M. (2012). Structural intermediates during alpha-synuclein fibrillogenesis on phospholipid vesicles. Journal of the American Chemical Society 134(11), 5090-5099.
41. CONWAY, K. A., HARPER, J.D. & LANSBURY, P.T. Jr. (2000). Fibrils formed in vitro from alpha-synuclein and two mutant forms linked to Parkinson's disease are typical amyloid. Biochemistry 39(10), 2552-2563.
42. CREMADES, N., COHEN, S. I., DEAS, E., ABRAMOV, A.Y., CHEN, A. Y., ORTE, A., SANDAL, M., CLARKE, R.W., DUNNE, P., APRILE, F. A., BERTONCINI, C.W., WOOD, N.W., KNOWLES, T. P., DOBSON, C.M. & KLENERMAN, D. (2012). Direct observation of the interconversion of normal and toxic forms of alphasynuclein. Cell 149(5), 1048-1059.
43. CUERVO, A. M., STEFANIS, L., FREDENBURG, R., LANSBURY, P.T. & SULZER, D. (2004). Impaired degradation of mutant alpha-synuclein by chaperonemediated autophagy. Science 305(5688), 1292-1295.
44. DANZER, K. M., KRANICH, L. R., RUF, W.P., CAGSAL-GETKIN, O., WINSLOW, A. R., ZHU, L., VANDERBURG, C.R. & MCLEAN, P. J. (2012). Exosomal cell-to-cell transmission of alpha synuclein oligomers. Molecular Neurodegeneration 7, 42.
45. DANZER, K. M., KREBS, S. K., WOLFF, M., BIRK, G. & HENGERER, B. (2009). Seeding induced by alphasynuclein oligomers provides evidence for spreading of alpha-synuclein pathology. Journal of Neurochemistry 111 (1), 192-203.
46. DAVIDSON, W. S., JONAS, A., CLAYTON, D.F. & GEORGE, J. M. (1998). Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. Journal of Biological Chemistry 273(16), 9443-9449.
47. DE FRANCESCHI, G., FRARE, E., PIVATO, M., RELINI, A., PENCO, A., GREGGIO, E., BUBACCO, L., FONTANA, A. & DE LAURETO, P. P. (2011). Structural and morphological characterization of aggregated species of alpha-synuclein induced by docosahexaenoic acid. Journal of Biological Chemistry 286(25), 22262-22274.
48. DEDMON, M. M., CHRISTODOULOU, J., WILSON, M.R. & DOBSON, C.M. (2005a). Heat shock protein 70 inhibits alpha-synuclein fibril formation via preferential binding to prefibrillar species. Journal of Biological Chemistry 280 (15), 14733-14740.
49. DEDMON, M. M., LINDORFF-LARSEN, K., CHRISTODOULOU, J., VENDRUSCOLO, M. & DOBSON, C. M. (2005b). Mapping long-range interactions in alphasynuclein using spin-label NMR and ensemble molecular dynamics simulations. Journal of the American Chemical Society 127(2), 476-477.
50. DER-SARKISSIAN, A., JAO, C. C., CHEN, J. & LANGEN, R. (2003). Structural organization of alpha-synuclein fibrils studied by site-directed spin labeling. Journal of Biological Chemistry 278(39), 37530-37535.
51. DESPLATS, P., LEE, H. J., BAE, E. J., PATRICK, C., ROCKENSTEIN, E., CREWS, L., SPENCER, B., MASLIAH, E. & LEE, S. J. (2009). Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proceedings of the National Academy of Sciences United States of America 106(31), 13010-13015.
52. DEVI, L., RAGHAVENDRAN, V., PRABHU, B. M., AVADHANI, N.G. & ANANDATHEERTHAVARADA, H.K. (2008). Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. Journal of Biological Chemistry 283(14), 9089-9100.
53. DICKSON, D.W. (2007). Linking selective vulnerability to cell death mechanisms in Parkinson's disease. American Journal of Pathology 170(1), 16-19.
54. DOBSON, C.M. (1999). Protein misfolding, evolution and disease. Trends in Biochemical Science 24(9), 329-332.
55. DUDA, J. E., GIASSON, B. I., CHEN, Q., GUR, T. L., HURTIG, H. I., STERN, M. B., GOLLOMP, S. M., ISCHIROPOULOS, H., LEE, V.M. & TROJANOWSKI, J.Q. (2000). Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies. American Journal of Pathology 157(5), 1439-1445.
56. DUSA, A., KAYLOR, J., EDRIDGE, S., BODNER, N., HONG, D. P. & FINK, A. L. (2006). Characterization of oligomers during alpha-synuclein aggregation using intrinsic tryptophan fluorescence. Biochemistry 45(8), 2752-2760.
57. EBRAHIMI-FAKHARI, D., WAHLSTER, L. & MCLEAN, P.J. (2012). Protein degradation pathways in Parkinson's disease: curse or blessing. Acta Neuropathology 124(2), 153-172.
58. EL-AGNAF, O. M., PALEOLOGOU, K. E., GREER, B., ABOGREIN, A. M., KING, J. E., SALEM, S. A., FULLWOOD, N. J., BENSON, F. E., HEWITT, R., FORD, K. J., MARTIN, F. L., HARRIOTT, P., COOKSON, M.R. & ALLSOP, D. (2004). A strategy for designing inhibitors of alpha-synuclein aggregation and toxicity as a novel treatment for Parkinson's disease and related disorders. FASEB Journal 18(11), 1315-1317.
59. ENGELENDER, S., KAMINSKY, Z., GUO, X., SHARP, A. H., AMARAVI, R. K., KLEIDERLEIN, J. J., MARGOLIS, R. L., TRONCOSO, J. C., LANAHAN, A. A., WORLEY, P.F., DAWSON, V. L., DAWSON, T.M. & ROSS, C. A. (1999).Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions. Nature Genetics 22(1), 110-114.
60. ESPOSITO, A., DOHM, C. P., KERMER, P., BAHR, M. & WOUTERS, F. S. (2007). alpha-Synuclein and its disease-related mutants interact differentially with the microtubule protein tau and associate with the actin cytoskeleton. Neurobiology of Disease 26(3), 521-531.
61. FAUVET, B., FARES, M. B., SAMUEL, F., DIKIY, I., TANDON, A., ELIEZER, D. & LASHUEL, H. A. (2012a). Characterization of semisynthetic and naturally Nalpha-acetylated alpha-synuclein in vitro and in intact cells: implications for aggregation and cellular properties of alpha-synuclein. Journal of Biological Chemistry 287(34), 28243-28262.
62. FAUVET, B., MBEFO, M. K., FARES, M. B., DESOBRY, C., MICHAEL, S., ARDAH, M. T., TSIKA, E., COUNE, P., PRUDENT, M., LION, N., ELIEZER, D., MOORE, D. J., SCHNEIDER, B., AEBISCHER, P., EL-AGNAF, O. M., MASLIAH, E. & LASHUEL, H. A. (2012b).alpha-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. Journal of Biological Chemistry 287(19), 15345-15364.
63. FENG, L. R., FEDEROFF, H. J., VICINI, S. & MAGUIRE-ZEISS, K. A. (2010). Alpha-synuclein mediates alterations in membrane conductance: a potential role for alpha-synuclein oligomers in cell vulnerability. European Journal of Neuroscience 32(1), 10-17.
64. FERREON, A. C., GAMBIN, Y., LEMKE, E.A. & DENIZ, A.A. (2009). Interplay of alpha-synuclein binding and conformational switching probed by single-molecule fluorescence. Proceedings of the National Academy of Sciences United States of America 106(14), 5645-5650.
65. FREDENBURG, R. A., ROSPIGLIOSI, C., MERAY, R. K., KESSLER, J. C., LASHUEL, H. A., ELIEZER, D. & LANSBURY, P. T. Jr. (2007). The impact of the E46K mutation on the properties of alpha-synuclein in its monomeric and oligomeric states. Biochemistry 46(24), 7107-7118.
66. FREEMAN D., CEDILLOS, R., CHOYKE, S., LUKIC, Z., MCGUIRE, K., MARVIN, S., BURRAGE, A. M., SUDHOLT, S., RANA, A., O'CONNOR, C., WIETHOFF, C. M. & CAMPBELL, E.M. (2013). Alpha-synuclein induces lysosomal rupture and cathepsin dependent reactive oxygen species following endocytosis. PLoS ONE 8 4 e62143.
67. FREUNDT, E. C., MAYNARD, N., CLANCY, E. K., ROY, S., BOUSSET, L., SOURIGUES, Y., COVERT, M., MELKI, R., KIRKEGAARD, K. & BRAHIC, M. (2012). Neuronto-neuron transmission of alpha-synuclein fibrils through axonal transport. Annals of Neurology 72(4), 517-524.
68. FUCHS, J., TICHOPAD, A., GOLUB, Y., MUNZ, M., SCHWEITZER, K. J., WOLF, B., BERG, D., MUELLER, J.C. & GASSER, T. (2008). Genetic variability in the SNCA gene influences alpha-synuclein levels in the blood and brain. FASEB Journal 22(5), 1327-1334.
69. FUJIWARA, H., HASEGAWA, M., DOHMAE, N., KAWASHIMA, A., MASLIAH, E., GOLDBERG, M. S., SHEN, J., TAKIO, K. & IWATSUBO, T. (2002). alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nature Cell Biology 4(2), 160-164.
70. FUNAYAMA, M., HASEGAWA, K., KOWA, H., SAITO, M., TSUJI, S. & OBATA, F. (2002). A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1. Annals of Neurology 51(3), 296-301.
71. GEORGIEVA, E. R., RAMLALL, T. F., BORBAT, P. P., FREED, J. H. & ELIEZER, D. (2010). The lipid-binding domain of wild type and mutant alpha-synuclein: compactness and interconversion between the broken and extended helix forms. Journal of Biological Chemistry 285(36), 28261-28274.
72. 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. (2000). Oxidative damage linked to neurodegeneration by selective alphasynuclein nitration in synucleinopathy lesions. Science 290 (5493), 985-989.
73. GIASSON, B. I., MURRAY, I. V., TROJANOWSKI, J.Q. & LEE, V.M. (2001). A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. Journal of Biological Chemistry 276 (4), 2380-2386.
74. GIEHM, L., LORENZEN, N. & OTZEN, D. E. (2011a). Assays for alpha-synuclein aggregation. Methods 53(3), 295-305.
75. GIEHM, L. & OTZEN, D. E. (2010). Strategies to increase the reproducibility of protein fibrillization in plate reader assays. Analytical Biochemistry 400(2), 270-281.
76. GIEHM, L., SVERGUN, D. I., OTZEN, D.E. & VESTERGAARD, B. (2011b). Low-resolution structure of a vesicle disrupting α-synuclein oligomer that accumulates during fibrillation. Proceedings of the National Academy of Sciences United States of America 108(8), 3246-3251.
77. GOERS, J., UVERSKY, V.N. & FINK, A. L. (2003). Polycation-induced oligomerization and accelerated fibrillation of human alpha-synuclein in vitro. Protein Science 12(4), 702-707.
78. GOSAVI, N., LEE, H. J., LEE, J. S., PATEL, S. & LEE, S. J. (2002). Golgi fragmentation occurs in the cells with prefibrillar alpha-synuclein aggregates and precedes the formation of fibrillar inclusion. Journal of Biological Chemistry 277(50), 48984-48992.
79. GOUSSET, K., SCHIFF, E., LANGEVIN, C., MARIJANOVIC, Z., CAPUTO, A., BROWMAN, D. T., CHENOUARD, N., DE CHAUMONT, F., MARTINO, A., ENNINGA, J., OLIVO-MARIN, J. C., MANNEL, D. & ZURZOLO, C. (2009). Prions hijack tunnelling nanotubes for intercellular spread. Nature Cell Biology 11(3), 328-336.
80. GRETEN-HARRISON, B., POLYDORO, M., MORIMOTO-TOMITA, M., DIAO, L., WILLIAMS, A. M., NIE, E. H., MAKANI, S., TIAN, N., CASTILLO, P. E., BUCHMAN, V.L. & CHANDRA, S. S. (2010). alphabetagamma-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction. Proceedings of the National Academy of Sciences United States of America 107 (45), 19573-19578.
81. GROENNING, M. (2010). Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils-current status. Journal of Chemical Biology 3(1), 1-18.
82. GURRY, T., ULLMAN, O., FISHER, C. K., PEROVIC, I., POCHAPSKY, T. & STULTZ, C.M. (2013). The dynamic structure of alpha-synuclein multimers. Journal of the American Chemical Society 135(10), 3865-3872.
83. HALLE, A., HORNUNG, V., PETZOLD, G. C., STEWART, C. R., MONKS, B. G., REINHECKEL, T., FITZGERALD, K. A., LATZ, E., MOORE, K.J. & GOLENBOCK, D. T. (2008). The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nature Immunology 9(8), 857-865.
84. HANSEN, C., ANGOT, E., BERGSTROM, A. L., STEINER, J. A., PIERI, L., PAUL, G., OUTEIRO, T. F., MELKI, R., KALLUNKI, P., FOG, K., LI, J.Y. & BRUNDIN, P. (2011). alpha-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. Journal of Clinical Investigation 121 (2), 715-725.
85. HEARPS, A. C., PRYOR, M. J., KUUSISTO, H.V., RAWLINSON, S. M., PILLER, S.C. & JANS, D. A. (2007). The biarsenical dye Lumio exhibits a reduced ability to specifically detect tetracysteine-containing proteins within live cells. Journal of Fluorescence 17(6), 593-597.
86. HEISE, H., HOYER, W., BECKER, S., ANDRONESI, O. C., RIEDEL, D. & BALDUS, M. (2005). Molecular-level secondary structure, polymorphism, and dynamics of full-length alpha-synuclein fibrils studied by solid-state NMR. Proceedings of the National Academy of Sciences United States of America 102(44), 15871-15876.
87. HERVAS, R., OROZ, J., GALERA-PRAT, A., GONI, O., VALBUENA, A., VERA, A. M., GOMEZ-SICILIA, A., LOSADA-URZAIZ, F., UVERSKY, V. N., MENENDEZ, M., LAURENTS, D. V., BRUIX, M. & CARRION-VAZQUEZ, M. (2012). Common features at the start of the neurodegeneration cascade. PLoS Biology 10(5), e1001335.
88. HIRSCH, E., GRAYBIEL, A.M. & AGID, Y. A. (1988). Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature 334(6180), 345-348.
89. HOYER, W., ANTONY, T., CHERNY, D., HEIM, G., JOVIN, T. M. & SUBRAMANIAM, V. (2002). Dependence of alphasynuclein aggregate morphology on solution conditions. Journal of Molecular Biology 322(2), 383-393.
90. HUDSON, S. A., ECROYD, H., KEE, T.W. & CARVER, J.A. (2009). The thioflavin T fluorescence assay for amyloid fibril detection can be biased by the presence of exogenous compounds. FEBS Journal 276(20), 5960-5972.
91. JAO, C. C., HEGDE, B. G., CHEN, J., HAWORTH, I.S. & LANGEN, R. (2008). Structure of membrane-bound alpha-synuclein from site-directed spin labeling and computational refinement. Proceedings of the National Academy of Sciences United States of America 105(50), 19666-19671.
92. KAMINSKI SCHIERLE, G. S., BERTONCINI, C.W., CHAN, F.T., VAN DER GOOT, A. T., SCHWEDLER, S., SKEPPER, J., SCHLACHTER, S., VAN HAM, T., ESPOSITO, A., KUMITA, J. R., NOLLEN, E. A., DOBSON, C.M. & KAMINSKI, C. F. (2011). A FRET sensor for noninvasive imaging of amyloid formation in vivo. Chemphyschem 12(3), 673-680.
93. KANG, L., MORIARTY, G. M., WOODS, L. A., ASHCROFT, A. E., RADFORD, S.E. & BAUM, J. (2012). N-terminal acetylation of alpha-synuclein induces increased transient helical propensity and decreased aggregation rates in the intrinsically disordered monomer. Protein Science 21(7), 911-917.
94. KASTEN, M. & KLEIN, C. (2013). The many faces of alphasynuclein mutations. Movment Disorders 28(6), 697-701.
95. KAYLOR, J., BODNER, N., EDRIDGE, S., YAMIN, G., HONG, D.P. & FINK, A. L. (2005). Characterization of oligomeric intermediates in alpha-synuclein fibrillation: FRET studies of Y125W/Y133F/Y136F alphasynuclein. Journal of Molecular Biology 353(2), 357-372.
96. KHURANA, R., COLEMAN, C., IONESCU-ZANETTI, C., CARTER, S. A., KRISHNA, V., GROVER, R. K., ROY, R. & SINGH, S. (2005). Mechanism of thioflavin T binding to amyloid fibrils. Journal of Structural Biology 151(3), 229-238.
97. KHURANA, R., IONESCU-ZANETTI, C., POPE, M., LI, J., NIELSON, L., RAMIREZ-ALVARADO, M., REGAN, L., FINK, A.L. & CARTER, S. A. (2003). A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy. Biophysics Journal 85 (2), 1135-1144.
98. KHURANA, R., UVERSKY, V. N., NIELSEN, L. & FINK, A.L. (2001). Is Congo red an amyloid-specific dye? Journal of Biological Chemistry, 276(25), 22715-22721.
99. KIELY, A. P., ASI, Y. T., KARA, E., LIMOUSIN, P., LING, H., LEWIS, P., PROUKAKIS, C., QUINN, N., LEES, A. J., HARDY, J., REVESZ, T., HOULDEN, H. & HOLTON, J.L. (2013). alpha-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy? Acta Neuropathology, 125 (5), 753-769.
100. KIM, C., HO, D. H., SUK, J. E., YOU, S., MICHAEL, S., KANG, J., JOONG LEE, S., MASLIAH, E., HWANG, D., LEE, H. J. & LEE, S. J. (2013). Neuron-released oligomeric alpha-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nature Communications 4, 1562.
101. KIM, H. Y., CHO, M. K., KUMAR, A., MAIER, E., SIEBENHAAR, C., BECKER, S., FERNANDEZ, C. O., LASHUEL, H. A., BENZ, R., LANGE, A. & ZWECKSTETTER, M. (2009). Structural properties of poreforming oligomers of alpha-synuclein. Journal of the American Chemical Society 131(47), 17482-17489.
102. KIM, H. Y., CHO, M. K., RIEDEL, D., FERNANDEZ, C.O. & ZWECKSTETTER, M. (2008). Dissociation of amyloid fibrils of alpha-synuclein in supercooled water. Angewandte Chemie International Edition English 47(27), 5046-5048.
103. KLUCKEN, J., OUTEIRO, T. F., NGUYEN, P., MCLEAN, P. J. & HYMAN, B. T. (2006). Detection of novel intracellular alpha-synuclein oligomeric species by fluorescence lifetime imaging. FASEB Journal 20(12), 2050-2057.
104. KLUCKEN, J., SHIN, Y., MASLIAH, E., HYMAN, B.T. & MCLEAN, P. J. (2004). Hsp70 Reduces alpha-Synuclein Aggregation and Toxicity. Journal of Biological Chemistry 279(24), 25497-25502.
105. KOKHAN, V. S., AFANASYEVA, M.A. & VAN'KIN, G.I. (2012). alpha-Synuclein knockout mice have cognitive impairments. Behavioural Brain Research 231(1), 226-230.
106. KORDOWER, J. H., CHU, Y., HAUSER, R. A., FREEMAN, T.B. & OLANOW, C.W. (2008). Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nature Medicine 14(5), 504-506.
107. KOSTKA, M., HOGEN, T., DANZER, K. M., LEVIN, J., HABECK, M., WIRTH, A., WAGNER, R., GLABE, C. G., FINGER, S., HEINZELMANN, U., GARIDEL, P., DUAN, W., ROSS, C. A., KRETZSCHMAR, H. & GIESE, A. (2008). Single particle characterization of iron-induced poreforming alpha-synuclein oligomers. Journal of Biological Chemistry 283(16), 10992-11003.
108. KREBS, M. R., BROMLEY, E.H. & DONALD, A.M. (2005). The binding of thioflavin-T to amyloid fibrils: localisation and implications. Journal of Structural Biology 149 (1), 30-37.
109. KRUGER, R., KUHN, W., MULLER, T., WOITALLA, D., GRAEBER, M., KOSEL, S., PRZUNTEK, H., EPPLEN, J.T., SCHOLS, L. & RIESS, O. (1998). Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nature Genetics 18(2), 106-108.
110. LASHUEL, H.A. & LANSBURY, P. T. Jr. (2006). Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins? Quartely Review of Biophysics, 39(2), 167-201.
111. LASHUEL, H. A., PETRE, B. M., WALL, J., SIMON, M., NOWAK, R. J., WALZ, T. & LANSBURY, P. T. Jr. (2002). Alpha-synuclein, especially the Parkinson's diseaseassociated mutants, forms pore-like annular and tubular protofibrils. Journal of Molecular Biology 322(5), 1089-1102.
112. LEE, H. J., CHOI, C. & LEE, S. J. (2002). Membrane-bound alpha-synuclein has a high aggregation propensity and the ability to seed the aggregation of the cytosolic form. Journal of Biological Chemistry 277(1), 671-678.
113. LEMKAU, L. R., COMELLAS, G., KLOEPPER, K. D., WOODS, W. S., GEORGE, J.M. & RIENSTRA, C.M. (2012). Mutant protein A30P alpha-synuclein adopts wild-type fibril structure, despite slower fibrillation kinetics. Journal of Biological Chemistry 287(14), 11526-11532.
114. LEMKAU, L. R., COMELLAS, G., LEE, S.W., RIKARDSEN, L. K., WOODS, W. S., GEORGE, J.M. & RIENSTRA, C.M. (2013). Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K. PLoS ONE 8(3), e49750.
115. LEVINE, H. III. (1993). Thioflavine T interaction with synthetic Alzheimer's disease beta-amyloid peptides: detection of amyloid aggregation in solution. Protein Science 2(3), 404-410.
116. LI, J., UVERSKY, V.N. & FINK, A. L. (2001). Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein. Biochemistry 40 (38), 11604-11613.
117. LI, J. Y., ENGLUND, E., HOLTON, J. L., SOULET, D., HAGELL, P., LEES, A. J., LASHLEY, T., QUINN, N.P., REHNCRONA, S., BJORKLUND, A., WIDNER, H., REVESZ, T., LINDVALL, O. & BRUNDIN, P. (2008). Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nature Medicine 14(5), 501-503.
118. LIU, I. H., UVERSKY, V. N., MUNISHKINA, L. A., FINK, A. L., HALFTER, W. & COLE, G. J. (2005). Agrin binds alphasynuclein and modulates alpha-synuclein fibrillation. Glycobiology 15(12), 1320-1331.
119. LIU, S., NINAN, I., ANTONOVA, I., BATTAGLIA, F., TRINCHESE, F., NARASANNA, A., KOLODILOV, N., DAUER, W., HAWKINS, R.D. & ARANCIO, O. (2004). alpha-Synuclein produces a long-lasting increase in neurotransmitter release. EMBO Journal 23(22), 4506-4516.
120. LOWE, R., POUNTNEY, D. L., JENSEN, P. H., GAI, W.P. & VOELCKER, N. H. (2004). Calcium(II) selectively induces alpha-synuclein annular oligomers via interaction with the C-terminal domain. Protein Science 13(12), 3245-3252.
121. LUK, K. C., HYDE, E. G., TROJANOWSKI, J.Q. & LEE, V.M. (2007). Sensitive fluorescence polarization technique for rapid screening of alpha-synuclein oligomerization/fibrillization inhibitors. Biochemistry 46(44), 12522-12529.
122. LUK, K. C., KEHM, V., CARROLL, J., ZHANG, B., O'BRIEN, P., TROJANOWSKI, J.Q. & LEE, V.M. (2012). Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338(6109), 949-953.
123. LUK, K. C., SONG, C., O'BRIEN, P., STIEBER, A., BRANCH, J. R., BRUNDEN, K. R., TROJANOWSKI, J.Q. & LEE, V.M. (2009). Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proceedings of the National Academy of Sciences United States of America 106(47), 20051-20056.
124. MAGUIRE-ZEISS, K.A. & FEDEROFF, H. J. (2010). Future directions for immune modulation in neurodegenerative disorders: focus on Parkinson's disease. Journal of Neural Transmission 117(8), 1019-1025.
125. MAK, S. K., MCCORMACK, A. L., MANNING-BOG, A. B., CUERVO, A.M. & DI MONTE, D. A. (2010). Lysosomal degradation of alpha-synuclein in vivo. Journal of Biological Chemistry 285(18), 13621-13629.
126. MBEFO, M. K., PALEOLOGOU, K. E., BOUCHARABA, A., OUESLATI, A., SCHELL, H., FOURNIER, M., OLSCHEWSKI, D., YIN, G., ZWECKSTETTER, M., MASLIAH, E., KAHLE, P. J., HIRLING, H. & LASHUEL, H. A. (2010). Phosphorylation of synucleins by members of the Polo-like kinase family. Journal of Biological Chemistry 285(4), 2807-2822.
127. MCCLENDON, S., ROSPIGLIOSI, C.C. & ELIEZER, D. (2009). Charge neutralization and collapse of the C-terminal tail of alpha-synuclein at low pH. Protein Science 18(7), 1531-1540.
128. MCLEAN, P. J., KAWAMATA, H. & HYMAN, B. T. (2001). Alpha-synuclein-enhanced green fluorescent protein fusion proteins form proteasome sensitive inclusions in primary neurons. Neuroscience 104(3), 901-912.
129. MIDDLETON, E.R. & RHOADES, E. (2010). Effects of curvature and composition on alpha-synuclein binding to lipid vesicles. Biophysics Journal 99(7), 2279-2288.
130. MILLER, L. M., BOURASSA, M.W. & SMITH, R. J. (2013). FTIR spectroscopic imaging of protein aggregation in living cells. Biochimica et Biophysica Acta 1828(10), 2339-2346.
131. MORRIS, A. M., WATZKY, M.A. & FINKE, R.G. (2009). Protein aggregation kinetics, mechanism, and curvefitting: a review of the literature. Biochimica et Biophysica Acta 1794(3), 375-397.
132. MOSHAROV, E. V., STAAL, R. G., BOVE, J., PROU, D., HANANIYA, A., MARKOV, D., POULSEN, N., LARSEN, K. E., MOORE, C. M., TROYER, M. D., EDWARDS, R. H., PRZEDBORSKI, S. & SULZER, D. (2006). Alpha-synuclein overexpression increases cytosolic catecholamine concentration. Journal of Neuroscience 26(36), 9304-9311.
133. NAKAMURA, K., NEMANI, V. M., AZARBAL, F., SKIBINSKI, G., LEVY, J. M., EGAMI, K., MUNISHKINA, L., ZHANG, J., GARDNER, B., WAKABAYASHI, J., SESAKI, H., CHENG, Y., FINKBEINER, S., NUSSBAUM, R. L., MASLIAH, E. & EDWARDS, R. H. (2011). Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein. Journal of Biological Chemistry 286(23), 20710-20726.
134. NAKAMURA, K., NEMANI, V. M., WALLENDER, E. K., KAEHLCKE, K., OTT, M. & EDWARDS, R. H. (2008). Optical reporters for the conformation of alphasynuclein reveal a specific interaction with mitochondria. Journal of Neuroscience 28(47), 12305-12317.
135. NASSTROM, T., FAGERQVIST, T., BARBU, M., KARLSSON, M., NIKOLAJEFF, F., KASRAYAN, A., EKBERG, M., LANNFELT, L., INGELSSON, M. & BERGSTROM, J. (2011). The lipid peroxidation products 4-oxo-2-nonenal and 4-hydroxy-2-nonenal
136. NATH, S., MEUVIS, J., HENDRIX, J., CARL, S.A. & ENGELBORGHS, Y. (2010). Early aggregation steps in alpha-synuclein as measured by FCS and FRET: evidence for a contagious conformational change. Biophysics Journal 98(7), 1302-1311.
137. NECULA, M., CHIRITA, C.N. & KURET, J. (2003). Rapid anionic micelle-mediated alpha-synuclein fibrillization in vitro. Journal of Biological Chemistry 278(47), 46674-46680.
138. NEMANI, V. M., LU, W., BERGE, V., NAKAMURA, K., ONOA, B., LEE, M. K., CHAUDHRY, F. A., NICOLL, R.A. & EDWARDS, R. H. (2010). Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65(1), 66-79.
139. NONAKA, T., WATANABE, S. T., IWATSUBO, T. & HASEGAWA, M. (2010). Seeded aggregation and toxicity of {alpha}-synuclein and tau: cellular models of neurodegenerative diseases. Journal of Biological Chemistry 285 (45), 34885-34898.
140. OLZSCHA, H., SCHERMANN, S. M., WOERNER, A. C., PINKERT, S., HECHT, M. H., TARTAGLIA, G. G., VENDRUSCOLO, M., HAYER-HARTL, M., HARTL, F.U. & VABULAS, R.M. (2011). Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions. Cell 144(1), 67-78.
141. ORTE, A., BIRKETT, N. R., CLARKE, R.W., DEVLIN, G. L., DOBSON, C.M. & KLENERMAN, D. (2008). Direct characterization of amyloidogenic oligomers by singlemolecule fluorescence. Proceedings of the National Academy of Sciences United States of America 105(38), 14424-14429.
142. OUTEIRO, T. F., PUTCHA, P., TETZLAFF, J. E., SPOELGEN, R., KOKER, M., CARVALHO, F., HYMAN, B.T. & MCLEAN, P. J. (2008). Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS ONE 3(4), e1867.
143. PALEOLOGOU, K. E., OUESLATI, A., SHAKKED, G., ROSPIGLIOSI, C. C., KIM, H. Y., LAMBERTO, G. R., FERNANDEZ, C. O., SCHMID, A., CHEGINI, F., GAI, W. P., CHIAPPE, D., MONIATTE, M., SCHNEIDER, B. L., AEBISCHER, P., ELIEZER, D., ZWECKSTETTER, M., MASLIAH, E. & LASHUEL, H. A. (2010). Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. Journal of Neuroscience 30(9), 3184-3198.
144. PALEOLOGOU, K. E., SCHMID, A.W., ROSPIGLIOSI, C. C., KIM, H. Y., LAMBERTO, G. R., FREDENBURG, R. A., LANSBURY, P. T. Jr., FERNANDEZ, C. O., ELIEZER, D., ZWECKSTETTER, M. & LASHUEL, H. A. (2008). Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of alpha-synuclein. Journal of Biological Chemistry 283(24), 16895-16905.
145. PALOMAKI, J., VALIMAKI, E., SUND, J., VIPPOLA, M., CLAUSEN, P. A., JENSEN, K. A., SAVOLAINEN, K., MATIKAINEN, S. & ALENIUS, H. (2011). Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism. ACS Nano 5(9), 6861-6870.
146. PINOTSI, D., BUELL, A. K., DOBSON, C. M., KAMINSKI SCHIERLE, G.S. & KAMINSKI, C. F. (2013). A label-free, quantitative assay of amyloid fibril growth based on intrinsic fluorescence. ChemBioChem 14(7), 846-850.
147. PIVATO, M., DE FRANCESCHI, G., TOSATTO, L., FRARE, E., KUMAR, D., AIOANEI, D., BRUCALE, M., TESSARI, I., BISAGLIA, M., SAMORI, B., DE LAURETO, P.P. & BUBACCO, L. (2012). Covalent alpha-synuclein dimers: chemico-physical and aggregation properties. PLoS ONE 7(12), e50027.
148. PLOTEGHER, N. & CIVIERO, L. (2012). Neuronal autophagy, alpha-synuclein clearance, and LRRK2 regulation: a lost equilibrium in parkinsonian brain. Journal of Neuroscience 32(43), 14851-14853.
149. POLYMENIDOU, M. & CLEVELAND, D.W. (2012). Prion-like spread of protein aggregates in neurodegeneration. Journal of Experimental Medicine 209(5), 889-893.
150. 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., LAZZARINI, A. M., DUVOISIN, R. C., DI IORIO, G., GOLBE, L.I. & NUSSBAUM, R. L. (1997). Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276(5321), 2045-2047.
151. POUNTNEY, D. L., LOWE, R., QUILTY, M., VICKERS, J. C., VOELCKER, N.H. & GAI, W. P. (2004). Annular alphasynuclein species from purified multiple system atrophy inclusions. Journal of Neurochemistry 90(2), 502-512.
152. PRONCHIK, J., HE, X., GIURLEO, J.T. & TALAGA, D.S. (2010). In vitro formation of amyloid from alphasynuclein is dominated by reactions at hydrophobic interfaces. Journal of the American Chemical Society, 132 (28), 9797-9803.
153. PROUKAKIS, C., DUDZIK, C. G., BRIER, T., MACKAY, D. S., COOPER, J. M., MILLHAUSER, G. L., HOULDEN, H. & SCHAPIRA, A. H. (2013). A novel alpha-synuclein missense mutation in Parkinson disease. Neurology 80(11), 1062-1064.
154. QIN, Z., HU, D., HAN, S., HONG, D.P. & FINK, A.L. (2007a). Role of different regions of alpha-synuclein in the assembly of fibrils. Biochemistry 46(46), 13322-13330.
155. QIN, Z., HU, D., HAN, S., REANEY, S. H., DI MONTE, D.A. & FINK, A. L. (2007b). Effect of 4-hydroxy-2-nonenal modification on alpha-synuclein aggregation. Journal of Biological Chemistry 282(8), 5862-5870.
156. QUIST, A., DOUDEVSKI, I., LIN, H., AZIMOVA, R., NG, D., FRANGIONE, B., KAGAN, B., GHISO, J. & LAL, R. (2005). Amyloid ion channels: a common structural link for protein-misfolding disease. Proceedings of the National Academy of Sciences United States of America 102 (30), 10427-10432.
157. REKAS, A., KNOTT, R. B., SOKOLOVA, A., BARNHAM, K. J., PEREZ, K. A., MASTERS, C. L., DREW, S. C., CAPPAI, R., CURTAIN, C.C. & PHAM, C. L. (2010). The structure of dopamine induced alpha-synuclein oligomers. European Biophysics Journal 39(10), 1407-1419.
158. REYNOLDS, N. P., SORAGNI, A., RABE, M., VERDES, D., LIVERANI, E., HANDSCHIN, S., RIEK, R. & SEEGER, S. (2011). Mechanism of membrane interaction and disruption by alpha-synuclein. Journal of the American Chemical Society 133(48), 19366-19375.
159. RIES, J., UDAYAR, V., SORAGNI, A., HORNEMANN, S., NILSSON, K. P., RIEK, R., HOCK, C., EWERS, H., AGUZZI, A.A. & RAJENDRAN, L. (2013). Superresolution imaging of amyloid fibrils with binding-activated probes. ACS Chemical Neuroscience 4(7), 1057-1061.
160. ROBERTI, M. J., BERTONCINI, C.W., KLEMENT, R., JARES-ERIJMAN, E.A. & JOVIN, T.M. (2007). Fluorescence imaging of amyloid formation in living cells by a functional, tetracysteine-tagged alphasynuclein. Nature Methods 4(4), 345-351.
161. ROBERTI, M. J., FOLLING, J., CELEJ, M. S., BOSSI, M., JOVIN, T.M. & JARES-ERIJMAN, E. A. (2012). Imaging nanometer-sized alpha-synuclein aggregates by superresolution fluorescence localization microscopy. Biophysics Journal 102(7), 1598-1607.
162. ROBERTI, M. J., JOVIN, T.M. & JARES-ERIJMAN, E. (2011). Confocal fluorescence anisotropy and FRAP imaging of alpha-synuclein amyloid aggregates in living cells. PLoS ONE 6(8), e23338.
163. ROOSTAEE, A., BEAUDOIN, S., STASKEVICIUS, A. & ROUCOU, X. (2013). Aggregation and neurotoxicity of recombinant alpha-synuclein aggregates initiated by dimerization. Molecular Neurodegeneration 8, 5.
164. ROSS, C.A. & POIRIER, M. A. (2004). Protein aggregation and neurodegenerative disease. Nature Medicine 10 (Suppl), S10-S17.
165. RUSTOM, A., SAFFRICH, R., MARKOVIC, I., WALTHER, P. & GERDES, H. H. (2004). Nanotubular highways for intercellular organelle transport. Science 303(5660), 1007-1010.
166. SANDAL, M., VALLE, F., TESSARI, I., MAMMI, S., BERGANTINO, E., MUSIANI, F., BRUCALE, M., BUBACCO, L. & SAMORI, B. (2008). Conformational equilibria in monomeric alpha-synuclein at the singlemolecule level. PLoS Biology 6(1), e6.
167. SCHMIDT, F., LEVIN, J., KAMP, F., KRETZSCHMAR, H., GIESE, A. & BOTZEL, K. (2012). Single-channel electrophysiology reveals a distinct and uniform pore complex formed by alpha-synuclein oligomers in lipid membranes. PLoS ONE 7(8), e42545.
168. SERPELL, L. C., BERRIMAN, J., JAKES, R., GOEDERT, M. & CROWTHER, R. A. (2000). Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like crossbeta conformation. Proceedings of the National Academy of Sciences United States of America 97(9), 4897-4902.
169. SHIRAKASHI, Y., KAWAMOTO, Y., TOMIMOTO, H., TAKAHASHI, R. & IHARA, M. (2006). alpha-Synuclein is colocalized with 14-3-3 and synphilin-1 in A53T transgenic mice. Acta Neuropathology 112(6), 681-689.
170. SIEVERS, S. A., KARANICOLAS, J., CHANG, H.W., ZHAO, A., JIANG, L., ZIRAFI, O., STEVENS, J. T., MUNCH, J., BAKER, D. & EISENBERG, D. (2011). Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation. Nature 475(7354), 96-100.
171. 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, C., COOKSON, M. R., MUENTER, M., BAPTISTA, M., MILLER, D., BLANCATO, J., HARDY, J. & GWINN-HARDY, K. (2003). alpha-Synuclein locus triplication causes Parkinson's disease. Science 302(5646), 841.
172. SMITH, W.W., JIANG, H., PEI, Z., TANAKA, Y., MORITA, H., SAWA, A., DAWSON, V. L., DAWSON, T.M. & ROSS, C.A. (2005). Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant alpha-synuclein-induced toxicity. Human Molecular Genetics 14(24), 3801-3811.
173. SOUSA, V. L., BELLANI, S., GIANNANDREA, M., YOUSUF, M., VALTORTA, F., MELDOLESI, J. & CHIEREGATTI, E. (2009). {alpha}-synuclein and its A30P mutant affect actin cytoskeletal structure and dynamics. Molecular Biology of the Cell 20(16), 3725-3739.
174. SPILLANTINI, M. G., CROWTHER, R. A., JAKES, R., HASEGAWA, M. & GOEDERT, M. (1998). alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proceedings of the National Academy of Sciences United States of America 95(11), 6469-6473.
175. SPILLANTINI, M. G., SCHMIDT, M. L., LEE, V. M., TROJANOWSKI, J. Q., JAKES, R. & GOEDERT, M. (1997). Alpha-synuclein in Lewy bodies. Nature 388(6645), 839-840.
176. STEINER, J. A., ANGOT, E. & BRUNDIN, P. (2011). A deadly spread: cellular mechanisms of alphasynuclein transfer. Cell Death and Differentiation 18(9), 1425-1433.
177. STROFFEKOVA, K., PROENZA, C. & BEAM, K. G. (2001). The protein-labeling reagent FLASH-EDT2 binds not only to CCXXCC motifs but also non-specifically to endogenous cysteine-rich proteins. Pflugers Arch 442(6), 859-866.
178. SUK, J. E., LOKAPPA, S.B. & ULMER, T. S. (2010). The clustering and spatial arrangement of beta-sheet sequence, but not order, govern alpha-synuclein fibrillogenesis. Biochemistry 49(7), 1533-1540.
179. SULATSKAYA, A. I., KUZNETSOVA, I.M. & TUROVEROV, K.K. (2011). Interaction of thioflavin T with amyloid fibrils: stoichiometry and affinity of dye binding, absorption spectra of bound dye. Journal of Physical Chemistry B 115 (39), 11519-11524.
180. TAKEDA, A., MALLORY, M., SUNDSMO, M., HONER, W., HANSEN, L. & MASLIAH, E. (1998). Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders. American Journal of Pathology 152(2), 367-372.
181. TANAKA, Y., ENGELENDER, S., IGARASHI, S., RAO, R. K., WANNER, T., TANZI, R. E., SAWA, A., DAWSON, V. L., DAWSON, T.M. & ROSS, C. A. (2001). Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis. Human Molecular Genetics 10(9), 919-926.
182. TASCHENBERGER, G., TOLOE, J., TERESHCHENKO, J., AKERBOOM, J., WALES, P., BENZ, R., BECKER, S., OUTEIRO, T., LOOGER, L., BAHR, M., ZWECKSTETTER, M. & KUGLER, S. (2013). β-synuclein aggregates and induces neurodegeneration in dopaminergic neurons. Annals of Neurology 74(1), 109-118.
183. THIRUNAVUKKUARASU, S., JARES-ERIJMAN, E.A. & JOVIN, T. M. (2008). Multiparametric fluorescence detection of early stages in the amyloid protein aggregation of pyrene-labeled alpha-synuclein. Journal of Molecular Biology 378(5), 1064-1073.
184. TOSATTO, L., ANDRIGHETTI, A. O., PLOTEGHER, N., ANTONINI, V., TESSARI, I., RICCI, L., BUBACCO, L. & DALLA SERRA, M. (2012). Alpha-synuclein pore forming activity upon membrane association. Biochimica et Biophysica Acta 1818(11), 2876-2883.
185. TREXLER, A.J. & RHOADES, E. (2009). Alpha-synuclein binds large unilamellar vesicles as an extended helix. Biochemistry 48(11), 2304-2306.
186. TREXLER, A.J. & RHOADES, E. (2010). Single molecule characterization of alpha-synuclein in aggregation-prone states. Biophysics Journal 99(9), 3048-3055.
187. TREXLER, A. J. & RHOADES, E. (2012). N-Terminal acetylation is critical for forming alpha-helical oligomer of alpha-synuclein. Protein Science 21(5), 601-605.
188. TROJANOWSKI, J.Q. & LEE, V.M. (2003). Parkinson's disease and related alpha-synucleinopathies are brain amyloidoses. Annals of the New York Academy of Sciences 991, 107-110.
189. TSIGELNY, I. F., BAR-ON, P., SHARIKOV, Y., CREWS, L., HASHIMOTO, M., MILLER, M. A., KELLER, S. H., PLATOSHYN, O., YUAN, J.X. & MASLIAH, E. (2007). Dynamics of alpha-synuclein aggregation and inhibition of pore-like oligomer development by beta-synuclein. FEBS Journal 274(7), 1862-1877.
190. ULMER, T. S., BAX, A., COLE, N.B. & NUSSBAUM, R.L. (2005). Structure and dynamics of micelle-bound human alpha-synuclein. Journal of Biological Chemistry 280(10), 9595-9603.
191. UVERSKY, V. N., YAMIN, G., SOUILLAC, P. O., GOERS, J., GLASER, C.B. & FINK, A. L. (2002). Methionine oxidation inhibits fibrillation of human alpha-synuclein in vitro. FEBS Letter 517(1-3), 239-244.
192. VAN HAM, T. J., ESPOSITO, A., KUMITA, J. R., HSU, S.T., KAMINSKI SCHIERLE, G. S., KAMINSKI, C.F., DOBSON, C. M., NOLLEN, E.A. & BERTONCINI, C.W. (2010). Towards multiparametric fluorescent imaging of amyloid formation: studies of a YFP model of alphasynuclein aggregation. Journal of Molecular Biology 395(3), 627-642.
193. VAN RAAIJ, M. E., SEGERS-NOLTEN, I.M. & SUBRAMANIAM, V. (2006). Quantitative morphological analysis reveals ultrastructural diversity of amyloid fibrils from alpha-synuclein mutants. Biophysics Journal 91(11), L96-L98.
194. VAN RAAIJ, M. E., VAN GESTEL, J., SEGERS-NOLTEN, I. M., DE LEEUW, S.W. & SUBRAMANIAM, V. (2008). Concentration dependence of alpha-synuclein fibril length assessed by quantitative atomic force microscopy and statistical-mechanical theory. Biophysics Journal 95(10), 4871-4878.
195. VAN ROOIJEN, B. D., CLAESSENS, M.M. & SUBRAMANIAM, V. (2009a). Lipid bilayer disruption by oligomeric alphasynuclein depends on bilayer charge and accessibility of the hydrophobic core. Biochimica et Biophysica Acta 1788(6), 1271-1278.
196. VAN ROOIJEN, B. D., CLAESSENS, M.M. & SUBRAMANIAM, V. (2010). Membrane Permeabilization by Oligomeric alpha-Synuclein: In Search of the Mechanism. PLoS ONE, 5(12), e14292.
197. VAN ROOIJEN, B. D., VAN LEIJENHORST-GROENER, K. A., CLAESSENS, M.M. & SUBRAMANIAM, V. (2009b). Tryptophan fluorescence reveals structural features of alpha-synuclein oligomers. Journal of Molecular Biology 394(5), 826-833.
198. VILAR, M., CHOU, H. T., LUHRS, T., MAJI, S. K., RIEK-LOHER, D., VEREL, R., MANNING, G., STAHLBERG, H. & RIEK, R. (2008). The fold of alphasynuclein fibrils. Proceedings of the National Academy of Sciences United States of America 105(25), 8637-8642.
199. VOLLES, M. J.& LANSBURY, P. T. Jr. (2002). Vesicle permeabilization by protofibrillar alpha-synuclein is sensitive to Parkinson's disease-linked mutations and occurs by a pore-like mechanism. Biochemistry 41(14), 4595-4602.
200. 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. (2011). Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 72(1), 57-71.
201. WANG, W., PEROVIC, I., CHITTULURU, J., KAGANOVICH, A., NGUYEN, L. T., LIAO, J., AUCLAIR, J. R., JOHNSON, D., LANDERU, A., SIMORELLIS, A. K., JU, S., COOKSON, M. R., ASTURIAS, F. J., AGAR, J. N., WEBB, B. N., KANG, C., RINGE, D., PETSKO, G. A., POCHAPSKY, T.C. & HOANG, Q. Q. (2011). A soluble alpha-synuclein construct forms a dynamic tetramer. Proceedings of the National Academy of Sciences United States of America 108(43), 17797-17802.
202. WAXMAN, E.A. & GIASSON, B. I. (2010). A novel, highefficiency cellular model of fibrillar alpha-synuclein inclusions and the examination of mutations that inhibit amyloid formation. Journal of Neurochemistry 113(2), 374-388.
203. WEINREB, P. H., ZHEN, W., POON, A.W., CONWAY, K.A. & LANSBURY, P. T. Jr. (1996). NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. Biochemistry 35(43), 13709-13715.
204. WINNER, B., JAPPELLI, R., MAJI, S. K., DESPLATS, P. A., BOYER, L., AIGNER, S., HETZER, C., LOHER, T., VILAR, M., CAMPIONI, S., TZITZILONIS, C., SORAGNI, A., JESSBERGER, S., MIRA, H., CONSIGLIO, A., PHAM, E., MASLIAH, E., GAGE, F.H. & RIEK, R. (2011). In vivo demonstration that alpha-synuclein oligomers are toxic. Proceedings of the National Academy of Sciences United States of America, 108(10), 4194-4199.
205. WOLFE, L. S., CALABRESE, M. F., NATH, A., BLAHO, D.V., MIRANKER, A.D. & XIONG, Y. (2010). Protein-induced photophysical changes to the amyloid indicator dye thioflavin T. Proceedings of the National Academy of Sciences United States of America 107(39), 16863-16868.
206. WOOD, S. J., WYPYCH, J., STEAVENSON, S., LOUIS, J. C., CITRON, M. & BIERE, A. L. (1999). alpha-synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease. Journal of Biological Chemistry 274(28), 19509-19512.
207. WU, K.P. & BAUM, J. (2010). Detection of transient interchain interactions in the intrinsically disordered protein alpha-synuclein by NMR paramagnetic relaxation enhancement. Journal of the American Chemical Society 132 (16), 5546-5547.
208. WU, K. P., WEINSTOCK, D. S., NARAYANAN, C., LEVY, R.M. & BAUM, J. (2009). Structural reorganization of alpha-synuclein at low pH observed by NMR and REMD simulations. Journal of Molecular Biology 391(4), 784-796.
209. XIA, Q., LIAO, L., CHENG, D., DUONG, D. M., GEARING, M., LAH, J. J., LEVEY, A.I. & PENG, J. (2008). Proteomic identification of novel proteins associated with Lewy bodies. Frontiers in Bioscience 13, 3850-3856.
210. XU, J., KAO, S. Y., LEE, F. J., SONG, W., JIN, L.W. & YANKNER, B. A. (2002). Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nature Medicine 8(6), 600-606.
211. YAMIN, G., MUNISHKINA, L. A., KARYMOV, M. A., LYUBCHENKO, Y. L., UVERSKY, V.N. & FINK, A.L. (2005). Forcing nonamyloidogenic beta-synuclein to fibrillate. Biochemistry 44(25), 9096-9107.
212. YAMIN, G., UVERSKY, V.N. & FINK, A. L. (2003). Nitration inhibits fibrillation of human alpha-synuclein in vitro by formation of soluble oligomers. FEBS Letter 542(1-3), 147-152.
213. YAP, T. L., PFEFFERKORN, C.M. & LEE, J. C. (2011). Residue-specific fluorescent probes of alpha-synuclein: detection of early events at the N-and C-termini during fibril assembly. Biochemistry 50(12), 1963-1965.
214. YORITAKA, A., HATTORI, N., UCHIDA, K., TANAKA, M., STADTMAN, E.R. & MIZUNO, Y. (1996). Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proceedings of the National Academy of Sciences United States of America 93(7), 2696-2701.
215. YUSHCHENKO, D. A., FAUERBACH, J. A., THIRUNAVUKKUARASU, S., JARES-ERIJMAN, E.A. & JOVIN, T.M. (2010). Fluorescent ratiometric MFC probe sensitive to early stages of alpha-synuclein aggregation. Journal of the American Chemical Society 132(23), 7860-7861.
216. ZAKHAROV, S. D., HULLEMAN, J. D., DUTSEVA, E. A., ANTONENKO, Y. N., ROCHET, J.C. & CRAMER, W.A. (2007). Helical alpha-synuclein forms highly conductive ion channels. Biochemistry 46(50), 14369-14379.
217. ZARRANZ, J. J., ALEGRE, J., GOMEZ-ESTEBAN, J. C., LEZCANO, E., ROS, R., AMPUERO, I., VIDAL, L., HOENICKA, J., RODRIGUEZ, O., ATARES, B., LLORENS, V., GOMEZ TORTOSA, E., DEL SER, T., MUNOZ, D.G. & DE YEBENES, J. G. (2004). The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Annals of Neurology 55(2), 164-173.
218. ZIBAEE, S., JAKES, R., FRASER, G., SERPELL, L. C., CROWTHER, R.A. & GOEDERT, M. (2007). Sequence determinants for amyloid fibrillogenesis of human alpha-synuclein. Journal of Molecular Biology 374(2), 454-464.
219. ZIJLSTRA, N., BLUM, C., SEGERS-NOLTEN, I. M., CLAESSENS, M.M. & SUBRAMANIAM, V. (2012). Molecular composition of sub-stoichiometrically labeled alpha-synuclein oligomers determined by singlemolecule photobleaching. Angewandte Chemie International Edition English 51(35), 8821-8824.
220. ZIMPRICH, A., BENET-PAGES, A., STRUHAL, W., GRAF, E., ECK, S. H., OFFMAN, M. N., HAUBENBERGER, D., SPIELBERGER, S., SCHULTE, E. C., LICHTNER, P., ROSSLE, S. C., KLOPP, N., WOLF, E., SEPPI, K., PIRKER, W., PRESSLAUER, S., MOLLENHAUER, B., KATZENSCHLAGER, R., FOKI, T., HOTZY, C., REINTHALER, E., HARUTYUNYAN, A., KRALOVICS, R., PETERS, A., ZIMPRICH, F., BRUCKE, T., POEWE, W., AUFF, E., TRENKWALDER, C., ROST, B., RANSMAYR, G., WINKELMANN, J., MEITINGER, T. & STROM, T.M. (2011). A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. American Journal of Human Genetics 89(1), 168-175.