Glial innate immunity generated by non-aggregated alpha-synuclein in mouse: Differences between wild-type and Parkinson's disease-linked mutants

PLoS ONE

Volumn 5, Issue 10, 2010, Pages

  Roodveldt, Cintia ^a   Labrador Garrido, Adahir ^a   Gonzalez Rey, Elena ^b   Fernandez Montesinos, Rafael ^a   Caro, Marta ^b   Lachaud, Christian C ^a   Waudby, Christopher A ^c,d   Delgado, Mario ^b   Dobson, Christopher M ^c   Pozo, David ^a  

^a CSIC   (Spain)

^b INSTITUTO DE PARASITOLOGÍA Y BIOMEDICINA LÓPEZ NEYRA   (Spain)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; ALPHA SYNUCLEIN; CYTOKINE; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GLUTAMIC ACID; LYSINE; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MONOCYTE CHEMOTACTIC PROTEIN 1; MUTANT PROTEIN; PROLINE; RANTES; THREONINE; CHEMOKINE; PRIMER DNA;

ARTICLE; CONTROLLED STUDY; CYTOKINE RELEASE; DISEASE COURSE; GLIA CELL; IMMUNOREGULATION; INNATE IMMUNITY; MICROGLIA; MOUSE; NERVE CELL STIMULATION; NONHUMAN; PARKINSON DISEASE; PROTEIN AGGREGATION; PROTEIN VARIANT; WILD TYPE; ANIMAL; C57BL MOUSE; FLUORESCENT ANTIBODY TECHNIQUE; GENETICS; IMMUNOLOGY; NUCLEOTIDE SEQUENCE; PHAGOCYTOSIS; PHYSIOLOGY; POLYACRYLAMIDE GEL ELECTROPHORESIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ALPHA-SYNUCLEIN; ANIMALS; BASE SEQUENCE; CHEMOKINES; CYTOKINES; DNA PRIMERS; ELECTROPHORESIS, POLYACRYLAMIDE GEL; FLUORESCENT ANTIBODY TECHNIQUE; IMMUNITY, INNATE; MICE; MICE, INBRED C57BL; MICROGLIA; PARKINSON DISEASE; PHAGOCYTOSIS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 78149441914     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0013481     Document Type: Article

References (84)

1. Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 95: 6469-6473.
2. Croisier E, Moran LB, Dexter DT, Pearce RK, Graeber MB (2005) Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition. J Neuroinflammation 2: 14.
3. Eriksen JL, Wszolek Z, Petrucelli L (2005) Molecular pathogenesis of Parkinson disease. Arch Neurol 62: 353-357.
4. Moore DJ, West AB, Dawson VL, Dawson TM (2005) Molecular pathophys-iology of Parkinson's disease. Annu Rev Neurosci 28: 57-87.
5. Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75: 333-366.
6. Sung JY, Kim J, Paik SR, Park JH, Ahn YS, et al. (2001) Induction of neuronal cell death by Rab5A-dependent endocytosis of alpha-synuclein. J Biol Chem 276: 27441-27448.
7. Liu J, Zhou Y, Wang Y, Fong H, Murray TM, et al. (2007) Identification of proteins involved in microglial endocytosis of alpha-synuclein. J Proteome Res 6: 3614-3627.
8. Lee HJ, Patel S, Lee SJ (2005) Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci 25: 6016-6024.
9. Sung JY, Park SM, Lee CH, Um JW, Lee HJ, et al. (2005) Proteolytic cleavage of extracellular secreted a-synuclein via matrix metalloproteinases. J Biol Chem 280: 25216-25224.
10. Borghi R, Marchese R, Negro A, Marinelli L, Forloni G, et al. (2000) Full length alpha-synuclein is present in cerebrospinal fluid from Parkinson's disease and normal subjects. Neurosci Lett 287: 65-67.
11. El-Agnaf OM, Salem SA, Paleologou KE, Cooper LJ, Fullwood NJ, et al. (2003) Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma. FASEB J 17: 1945-1947.
12. Kim S, Seo JH, Suh YH (2004) Alpha-synuclein, Parkinson's disease, and Alzheimer's disease. Parkinsonism Relat Disord 10: S9-13.
13. Richter-Landsberg C, Gorath M, Trojanowski JQ, Lee VM (2000) alpha-synuclein is developmentally expressed in cultured rat brain oligodendrocytes. J Neurosci Res 62: 9-14.
14. Mori F, Tanji K, Yoshimoto M, Takahashi H, Wakabayashi K (2002) Demonstration of alpha-synuclein immunoreactivity in neuronal and glial cytoplasm in normal human brain tissue using proteinase K and formic acid pretreatment. Exp Neurol 176: 98-104.
15. Perez RG, Hastings TG (2004) Could a loss of alpha-synuclein function put dopaminergic neurons at risk? J Neurochem 89: 1318-1324.
16. Weinreb PH, Zhen W, Poon AW, Conway KA, Lansbury PT, Jr. (1996) NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. Biochemistry 35: 13709-13715.
17. Dedmon MM, Lindorff-Larsen K, Christodoulou J, Vendruscolo M, Dobson CM (2005) Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations. J Am Chem Soc 127: 476-477.
18. Bertoncini CW, Jung YS, Fernandez CO, Hoyer W, Griesinger C, et al. (2005) Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein. Proc Natl Acad Sci USA 102: 1430-1435.
19. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, et al. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276: 2045-2047.
20. Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, et al. (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 18: 106-108.
21. Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, et al. (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55: 164-173.
22. Gasser T (2005) Genetics of Parkinson's disease. Curr Opin Neurol 18: 363-369.
23. Bertoncini CW, Fernandez CO, Griesinger C, Jovin TM, Zweckstetter M (2005) Familial mutants of alpha-synuclein with increased neurotoxicity have a destabilized conformation. J Biol Chem 280: 30649-30652.
24. Cookson MR (2009) alpha-Synuclein and neuronal cell death. Mol Neurode-gener 4: 9.
25. Kim YS, Joh TH (2006) Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease. Exp Mol Med 38: 333-347.
26. McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 38: 1285-1291.
27. Forno LS (1996) Neuropathology of Parkinson's disease. J Neuropathol Exp Neurol 55: 259-272.
28. Banati RB, Daniel SE, Blunt SB (1998) Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease. Mov Disord 13: 221-227.
29. Knott C, Stern G, Wilkin GP (2000) Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol Cell Neurosci 16: 724-739.
30. Mirza B, Hadberg H, Thomsen P, Moos T (2000) The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease. Neuroscience 95: 425-432.
31. Vila M, Jackson-Lewis V, Guegan C, Wu DC, Teismann P, et al. (2001) The role of glial cells in Parkinson's disease. Curr Opin Neurol 14: 483-489.
32. Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, et al. (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 22: 1763-1771.
33. Delgado M, Ganea D (2003) Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson's disease by blocking microglial activation. FASEB J 17: 944-946.
34. Sanchez-Pernaute R, Ferree A, Cooper O, Yu M, Brownell AL, et al. (2004) Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease. J Neuroinflammation 1: 6.
35. Zhang W, Wang T, Pei Z, Miller DS, Wu X, et al. (2005) Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB J 19: 533-542.
36. Theodore S, Cao S, McLean PJ, Standaert DG (2008) Targeted overexpression of human alpha-synuclein triggers microglial activation and an adaptive immune response in a mouse model of Parkinson disease. J Neuropathol Exp Neurol 67: 1149-1158.
37. Su X, Maguire-Zeiss KA, Giuliano R, Prifti L, Venkatesh K, et al. (2008) Synuclein activates microglia in a model of Parkinson's disease. Neurobiol Aging 29: 1690-1701.
38. Chung CY, Koprich JB, Siddiqi H, Isacson O (2009) Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroin-flammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy. J Neurosci 29: 3365-3373.
39. Sanchez-Guajardo V, Febbraro F, Kirik D, Romero-Ramos M (2010) Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease. PLoS One 5: e8784.
40. Gu XL, Long CX, Sun L, Xie C, Lin X, et al. (2010) Astrocytic expression of Parkinson's disease-related A53T alpha-synuclein causes neurodegeneration in mice. Mol Brain 3: 12.
41. Roodveldt C, Christodoulou J, Dobson CM (2008) Immunological features of alpha-synuclein in Parkinson's disease. J Cell Mol Med 12: 1820-1829.
42. Lee SJ (2008) Origins and effects of extracellular alpha-synuclein: implications in Parkinson's disease. J Mol Neurosci 34: 17-22.
43. Benner EJ, Banerjee R, Reynolds AD, Sherman S, Pisarev VM, et al. (2008) Nitrated alpha-Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic Neurons. PLoS One 3: e1376.
44. Zhang W, Dallas S, Zhang D, Guo JP, Pang H, et al. (2007) Microglial PHOX and Mac-1 are essential to the enhanced dopaminergic neurodegeneration elicited by A30P and A53T mutant alpha-synuclein. Glia 55: 1178-1188.
45. Thomas MP, Chartrand K, Reynolds A, Vitvitsky V, Banerjee R, et al. (2007) Ion channel blockade attenuates aggregated alpha-synuclein induction of microglial reactive oxygen species: relevance for the pathogenesis of Parkinson's disease. J Neurochem 100: 503-519.
46. Reynolds AD, Glanzer JG, Kadiu I, Ricardo-Dukelow M, Chaudhuri A, et al. (2008) Nitrated alpha-synuclein-activated microglial profiling for Parkinson's disease. J Neurochem 104: 1504-1525.
47. Giasson BI, Duda JE, Murray IV, Chen Q, Souza JM, et al. (2000) Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 290: 985-989.
48. Souza JM, Giasson BI, Chen Q, Lee VM, 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.
49. Joo SH, Kwon KJ, Kim JW, Hasan MR, Lee HJ, et al. (2010) Regulation of matrix metalloproteinase-9 and tissue plasminogen activator activity by alpha-synuclein in rat primary glial cells. Neurosci Lett 469: 352-356.
50. Lee EJ, Woo MS, Moon PG, Baek MC, Choi IY, et al. (2010) Alpha-synuclein activates microglia by inducing the expressions of matrix metalloproteinases and the subsequent activation of protease-activated receptor-1. J Immunol 185: 615-623.
51. Park JY, Paik SR, Jou I, Park SM (2008) Microglial phagocytosis is enhanced by monomeric alpha-synuclein, not aggregated alpha-synuclein: implications for Parkinson's disease. Glia 56: 1215-1223.
52. Klegeris A, Pelech S, Giasson BI, Maguire J, Zhang H, et al. (2008) Alpha-synuclein activates stress signaling protein kinases in THP-1 cells and microglia. Neurobiol Aging 29: 739-752.
53. Klegeris A, Giasson BI, Zhang H, Maguire J, Pelech S, et al. (2006) Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells. FASEB J 20: 2000-2008.
54. Su X, Federoff HJ, Maguire-Zeiss KA (2009) Mutant alpha-Synuclein overexpression mediates early proinflammatory activity. Neurotox Res 16: 238-254.
55. Jensen PH, Hojrup P, Hager H, Nielsen MS, Jacobsen L, et al. (1997) Binding of Abeta to alpha- and beta-synucleins: identification of segments in alpha-synuclein/NAC precursor that bind Abeta and NAC. Biochem J 323: 539-546.
56. Cole NB, Murphy DD, Grider T, Rueter S, Brasaemle D, et al. (2002) Lipid droplet binding and oligomerization properties of the Parkinson's disease protein alpha-synuclein. J Biol Chem 277: 6344-6352.
57. Lashuel HA, Hartley D, Petre BM, Walz T, Lansbury PT, Jr. (2002) Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature 418: 291.
58. Moussa CE, Wersinger C, Rusnak M, Tomita Y, Sidhu A (2004) Abnormal migration of human wild-type alpha-synuclein upon gel electrophoresis. Neurosci Lett 371: 239-243.
59. Schagger H, von Jagow G (1991) Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form. Anal Biochem 199: 223-231.
60. El-Agnaf OM, Salem SA, Paleologou KE, Curran MD, Gibson MJ, et al. (2006) Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J 20: 419-425.
61. Long-Smith CM, Sullivan AM, Nolan YM (2009) The influence of microglia on the pathogenesis of Parkinson's disease. Prog Neurobiol 89: 277-287.
62. Reynolds AD, Stone DK, Mosley RL, Gendelman HE (2009) Nitrated a-synuclein-induced alterations in microglial immunity are regulated by CD4+ T cell subsets. J Immunol 182: 4137-4149.
63. Reynolds AD, Banerjee R, Liu J, Gendelman HE, Mosley RL (2007) Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease. J Leukoc Biol 82: 1083-1094.
64. Austin SA, Floden AM, Murphy EJ, Combs CK (2006) Alpha-synuclein expression modulates microglial activation phenotype. J Neurosci 26: 10558-10563.
65. Barreiro O, Martin P, Gonzalez-Amaro R, Sanchez-Madrid F (2010) Molecular cues guiding inflammatory responses. Cardiovasc Res 86: 174-182.
66. Schwartz M (2010) ''Tissue-repairing'' blood-derived macrophages are essential for healing of the injured spinal cord: From skin-activated macrophages to infiltrating blood-derived cells? Brain Behav Immun 24: 1054-1057.
67. Rich RR, Fleisher TA, Shearer WT, Shroeder HW, Jr., Frew AJ, Weyand CM (2008) Clinical Immunology. Principles and Practice TA F, ed. Elsevier Inc.
68. Rentzos M, Nikolaou C, Andreadou E, Paraskevas GP, Rombos A, et al. (2007) Circulating interleukin-15 and RANTES chemokine in Parkinson's disease. Acta Neurol Scand 116: 374-379.
69. Gangemi S, Basile G, Merendino RA, Epifanio A, Di Pasquale G, et al. (2003) Effect of levodopa on interleukin-15 and RANTES circulating levels in patients affected by Parkinson's disease. Mediators Inflamm 12: 251-253.
70. Reale M, Iarlori C, Thomas A, Gambi D, Perfetti B, et al. (2009) Peripheral cytokines profile in Parkinson's disease. Brain Behav Immun 23: 55-63.
71. Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, et al. (2002) IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 168: 3195-3204.
72. Stone DK, Reynolds AD, Mosley RL, Gendelman HE (2009) Innate and adaptive immunity for the pathobiology of Parkinson's disease. Antioxid Redox Signal 11: 2151-2166.
73. Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol 8: 382-397.
74. Colton CA, Wilcock DM (2010) Assessing Activation States in Microglia. CNS Neurol Disord Drug Targets 9: 174-191.
75. Bonifati V, Oostra BA, Heutink P (2004) Unraveling the pathogenesis of Parkinson's disease: the contribution of monogenic forms. Cell Mol Life Sci 61: 1729-1750.
76. Spira PJ, Sharpe DM, Halliday G, Cavanagh J, Nicholson GA (2001) Clinical and pathological features of a Parkinsonian syndrome in a family with an Ala53Thr alpha-synuclein mutation. Ann Neurol 49: 313-319.
77. Golbe LI, Di Iorio G, Sanges G, Lazzarini AM, La Sala S, et al. (1996) Clinical genetic analysis of Parkinson's disease in the Contursi kindred. Ann Neurol 40: 767-775.
78. Papapetropoulos S, Paschalis C, Athanassiadou A, Papadimitriou A, Ellul J, et al. (2001) Clinical phenotype in patients with alpha-synuclein Parkinson's disease living in Greece in comparison with patients with sporadic Parkinson's disease. J Neurol Neurosurg Psychiatry 70: 662-665.
79. Bostantjopoulou S, Katsarou Z, Papadimitriou A, Veletza V, Hatzigeorgiou G, et al. (2001) Clinical features of parkinsonian patients with the alpha-synuclein (G209A) mutation. Mov Disord 16: 1007-1013.
80. Mestas J, Hughes CC (2004) Of mice and not men: differences between mouse and human immunology. J Immunol 172: 2731-2738.
81. Hoyer W, Antony T, Cherny D, Heim G, Jovin TM, et al. (2002) Dependence of alpha-synuclein aggregate morphology on solution conditions. J Mol Biol 322: 383-393.
82. Candiano G, Bruschi M, Musante L, Santucci L, Ghiggeri GM, et al. (2004) Blue silver: a very sensitive colloidal Coomassie G-250 staining for proteome analysis. Electrophoresis 25: 1327-1333.
83. Wittig I, Braun HP, Schagger H (2006) Blue native PAGE. Nat Protoc 1: 418-428.
84. Saura J, Tusell JM, Serratosa J (2003) High-yield isolation of murine microglia by mild trypsinization. Glia 44: 183-189.