The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?

Brain Research

Volumn 1617, Issue , 2015, Pages 155-173

  Doty, Kevin R ^a   Guillot Sestier, Marie Victoire ^a   Town, Terrence ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

Alzheimer's disease; Amyotrophic lateral sclerosis; Central nervous system; Neuroimmunology; Neuroinflammation; Parkinson's disease

Indexed keywords

CHEMOKINE; CYTOKINE; MESSENGER RNA; AUTACOID;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; CELL INFILTRATION; DEGENERATIVE DISEASE; GENE EXPRESSION; GENETIC RISK; HUMAN; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; INNATE IMMUNITY; MOTONEURON; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; RNA SPLICING; SIGNAL TRANSDUCTION; ANIMAL; ASTROCYTE; BRAIN; ENCEPHALITIS; GENETICS; IMMUNOLOGY; METABOLISM; MICROGLIA; NERVE CELL; RISK FACTOR;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; ASTROCYTES; BRAIN; ENCEPHALITIS; HUMANS; INFLAMMATION MEDIATORS; MICROGLIA; NEURODEGENERATIVE DISEASES; NEURONS; PARKINSON DISEASE; RISK FACTORS;

EID: 84937634728     PISSN: 00068993     EISSN: 18726240     Source Type: Journal    
DOI: 10.1016/j.brainres.2014.09.008     Document Type: Review

References (235)

1. B. Ajami, J.L. Bennett, C. Krieger, W. Tetzlaff, and F.M.V. Rossi Local self-renewal can sustain CNS microglia maintenance and function throughout adult life Nat. Neurosci. 10 2007 1538 1543 10.1038/nn2014
2. H. Akiyama Inflammation and Alzheimer's disease Neurobiol. Aging 21 2000 383 421 10.1016/S0197-4580(00)00124-X
3. R.S. Akundi, Z. Huang, J. Eason, J.D. Pandya, L. Zhi, W.A. Cass, P.G. Sullivan, and H. Büeler Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice PLoS One 6 2011 e16038 10.1371/journal.pone.0016038
4. S. Apolloni, C. Parisi, M.G. Pesaresi, S. Rossi, M.T. Carrì, M. Cozzolino, C. Volonté, and N. D'Ambrosi The NADPH oxidase pathway is dysregulated by the P2X7 receptor in the SOD1-G93A microglia model of amyotrophic lateral sclerosis J. Immunol. 190 2013 5187 5195 10.4049/jimmunol.1203262
5. S.H. Appel, W. Zhao, D.R. Beers, and J.S. Henkel The microglial-motoneuron dialogue in ALS Acta Myol. 30 2011 4 8
6. S.A. Austin, A.M. Floden, E.J. Murphy, and C.K. Combs Alpha-synuclein expression modulates microglial activation phenotype J. Neurosci. 26 2006 10558 10563 10.1523/JNEUROSCI.1799-06.2006
7. R.B. Banati, S.E. Daniel, and S.B. Blunt Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease Mov. Disord. 13 1998 221 227 10.1002/mds.870130205
8. R. Bandopadhyay, A.E. Kingsbury, M.R. Cookson, A.R. Reid, I.M. Evans, A.D. Hope, A.M. Pittman, T. Lashley, R. Canet-Aviles, D.W. Miller, C. McLendon, C. Strand, A.J. Leonard, P.M. Abou-Sleiman, D.G. Healy, H. Ariga, N.W. Wood, R. de Silva, T. Revesz, J.A. Hardy, and A.J. Lees The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease Brain 127 2004 420 430 10.1093/brain/awh054
9. K.J. Barnham, C.L. Masters, and A.I. Bush Neurodegenerative diseases and oxidative stress Nat. Rev. Drug Discov. 3 2004 205 214 10.1038/nrd1330
10. D.R. Beers, J.S. Henkel, Q. Xiao, W. Zhao, J. Wang, A.A. Yen, L. Siklos, S.R. McKercher, and S.H. Appel Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis Proc. Natl. Acad. Sci. U. S. A 103 2006 16021 16026 10.1073/pnas.0607423103
11. D.R. Beers, J.S. Henkel, W. Zhao, J. Wang, and S.H. Appel CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS Proc. Natl. Acad. Sci. U. S. A 105 2008 15558 15563 10.1073/pnas.0807419105
12. D.R. Beers, J.S. Henkel, W. Zhao, J. Wang, A. Huang, S. Wen, B. Liao, and S.H. Appel Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis Brain 134 2011 1293 1314 10.1093/brain/awr074
13. D. Béraud, M. Twomey, B. Bloom, A. Mittereder, V. Ton, K. Neitzke, S. Chasovskikh, T.R. Mhyre, and K.A. Maguire-Zeiss α-Synuclein alters toll-like receptor expression Front. Neurosci. 5 2011 80 10.3389/fnins.2011.00080
14. D. Blum-Degen, T. Müller, W. Kuhn, M. Gerlach, H. Przuntek, and P. Riederer Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients Neurosci. Lett. 202 1995 17 20
15. S. Boillée, K. Yamanaka, C.S. Lobsiger, N.G. Copeland, N.A. Jenkins, G. Kassiotis, G. Kollias, and D.W. Cleveland Onset and progression in inherited ALS determined by motor neurons and microglia Science 312 2006 1389 1392 10.1126/science.1123511
16. G. Boka, P. Anglade, D. Wallach, F. Javoy-Agid, Y. Agid, and E.C. Hirsch Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease Neurosci. Lett. 172 1994 151 154
17. A.-K. Bouzier-Sore, and L. Pellerin Unraveling the complex metabolic nature of astrocytes Front. Cell. Neurosci. 7 2013 179 10.3389/fncel.2013.00179
18. M. Bowerman, T. Vincent, F. Scamps, F.E. Perrin, W. Camu, and C. Raoul Neuroimmunity dynamics and the development of therapeutic strategies for amyotrophic lateral sclerosis Front. Cell. Neurosci. 7 2013 214 10.3389/fncel.2013.00214
19. J.C. Breitner, L.D. Baker, T.J. Montine, C.L. Meinert, C.G. Lyketsos, K.H. Ashe, J. Brandt, S. Craft, D.E. Evans, R.C. Green, M.S. Ismail, B.K. Martin, M.J. Mullan, M. Sabbagh, and P.N. Tariot Extended results of the Alzheimer's disease anti-inflammatory prevention trial Alzheimers. Dement. 7 2011 402 411 10.1016/j.jalz.2010.12.014
20. V. Brochard, B. Combadière, A. Prigent, Y. Laouar, A. Perrin, V. Beray-Berthat, O. Bonduelle, D. Alvarez-Fischer, J. Callebert, J.-M. Launay, C. Duyckaerts, R.A. Flavell, E.C. Hirsch, and S. Hunot Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease J. Clin. Investig. 119 2009 182 192 10.1172/JCI36470
21. N.C. Burton, T.W. Kensler, and T.R. Guilarte In vivo modulation of the Parkinsonian phenotype by Nrf2 Neurotoxicology 27 2006 1094 1100 10.1016/j.neuro.2006.07.019
22. B. Cameron, W. Tse, R. Lamb, X. Li, B.T. Lamb, and G.E. Landreth Loss of interleukin receptor-associated kinase 4 signaling suppresses amyloid pathology and alters microglial phenotype in a mouse model of Alzheimer's disease J. Neurosci. 32 2012 15112 15123 10.1523/JNEUROSCI.1729-12.2012
23. M. Casula, A.M. Iyer, W.G.M. Spliet, J.J. Anink, K. Steentjes, M. Sta, D. Troost, and E. Aronica Toll-like receptor signaling in amyotrophic lateral sclerosis spinal cord tissue Neuroscience 179 2011 233 243 10.1016/j.neuroscience.2011.02.001
24. P. Chakrabarty, A. Herring, C. Ceballos-Diaz, P. Das, and T.E. Golde Hippocampal expression of murine TNFα results in attenuation of amyloid deposition in vivo Mol. Neurodegener. 6 2011 16 10.1186/1750-1326-6-16
25. P. Chakrabarty, K. Jansen-West, A. Beccard, C. Ceballos-Diaz, Y. Levites, C. Verbeeck, A.C. Zubair, D. Dickson, T.E. Golde, and P. Das Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition FASEB J. 24 2010 548 559 10.1096/fj.09-141754
26. C.C. Chao, T.A. Ala, S. Hu, K.B. Crossley, R.E. Sherman, P.K. Peterson, and W.H. Frey Serum cytokine levels in patients with Alzheimer's disease Clin. Diagn. Lab. Immunol. 1 1994 433 436
27. C.C. Chao, S. Hu, W.H. Frey, T.A. Ala, W.W. Tourtellotte, and P.K. Peterson Transforming growth factor beta in Alzheimer's disease Clin. Diagn. Lab. Immunol. 1 1994 109 110
28. P.-C. Chen, M.R. Vargas, A.K. Pani, R.J. Smeyne, D.A. Johnson, Y.W. Kan, and J.A. Johnson Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: critical role for the astrocyte Proc. Natl. Acad. Sci. U. S. A 106 2009 2933 2938 10.1073/pnas.0813361106
29. P.-S. Chen, G.-S. Peng, G. Li, S. Yang, X. Wu, C.-C. Wang, B. Wilson, R.-B. Lu, P.-W. Gean, D.-M. Chuang, and J.-S. Hong Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes Mol. Psychiatry 11 2006 1116 1125 10.1038/sj.mp.4001893
30. W.-S. Chung, L.E. Clarke, G.X. Wang, B.K. Stafford, A. Sher, C. Chakraborty, J. Joung, L.C. Foo, A. Thompson, C. Chen, S.J. Smith, and B.A. Barres Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways Nature 504 2013 394 400 10.1038/nature12776
31. L.E. Clarke, and B.A. Barres Emerging roles of astrocytes in neural circuit development Nat. Rev. Neurosci. 14 2013 311 321 10.1038/nrn3484
32. A.M. Clement, M.D. Nguyen, E.A. Roberts, M.L. Garcia, S. Boillée, M. Rule, A.P. McMahon, W. Doucette, D. Siwek, R.J. Ferrante, R.H. Brown, J.-P. Julien, L.S.B. Goldstein, and D.W. Cleveland Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice Science 302 2003 113 117 10.1126/science.1086071
33. Colangelo, A.M., Alberghina, L., Papa, M., 2014. Astrogliosis as a therapeutic target for neurodegenerative diseases. Neurosci. Lett. 10.1016/j.neulet.2014.01.014
34. D.B. Constam, J. Philipp, U. V Malipiero, P. ten Dijke, M. Schachner, and A. Fontana Differential expression of transforming growth factor-beta 1, -beta 2, and -beta 3 by glioblastoma cells, astrocytes, and microglia J. Immunol. 148 1992 1404 1410
35. M.R. Cookson alpha-Synuclein and neuronal cell death Mol. Neurodegener. 4 2009 9 10.1186/1750-1326-4-9
36. J.T. Coyle, and P. Puttfarcken Oxidative stress, glutamate, and neurodegenerative disorders Science 262 1993 689 695
37. D. Culpan, S.H. MacGowan, J.M. Ford, J.A.R. Nicoll, W.S. Griffin, D. Dewar, N.J. Cairns, A. Hughes, P.G. Kehoe, and G.K. Wilcock Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease Neurosci. Lett. 350 2003 61 65
38. C.L. Cunningham, V. Martínez-Cerdeño, and S.C. Noctor Microglia regulate the number of neural precursor cells in the developing cerebral cortex J. Neurosci. 33 2013 4216 4233 10.1523/JNEUROSCI.3441-12.2013
39. D. Davalos, J. Grutzendler, G. Yang, J. V Kim, Y. Zuo, S. Jung, D.R. Littman, M.L. Dustin, and W.-B. Gan ATP mediates rapid microglial response to local brain injury in vivo Nat. Neurosci. 8 2005 752 758 10.1038/nn1472
40. M. DeJesus-Hernandez, I.R. Mackenzie, B.F. Boeve, A.L. Boxer, M. Baker, N.J. Rutherford, A.M. Nicholson, N.A. Finch, H. Flynn, J. Adamson, N. Kouri, A. Wojtas, P. Sengdy, G.-Y.R. Hsiung, A. Karydas, W.W. Seeley, K.A. Josephs, G. Coppola, D.H. Geschwind, Z.K. Wszolek, H. Feldman, D.S. Knopman, R.C. Petersen, B.L. Miller, D.W. Dickson, K.B. Boylan, N.R. Graff-Radford, and R. Rademakers Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS Neuron 72 2011 245 256 10.1016/j.neuron.2011.09.011
41. M. Deleidi, and T. Gasser The role of inflammation in sporadic and familial Parkinson's disease Cell. Mol. Life Sci. 70 2013 4259 4273 10.1007/s00018-013-1352-y
42. F. Di Virgilio, S. Ceruti, P. Bramanti, and M.P. Abbracchio Purinergic signalling in inflammation of the central nervous system Trends Neurosci. 32 2009 79 87 10.1016/j.tins.2008.11.003
43. R.J. Dobbs, A. Charlett, A.G. Purkiss, S.M. Dobbs, C. Weller, and D.W. Peterson Association of circulating TNF-alpha and IL-6 with ageing and parkinsonism Acta Neurol. Scand. 100 1999 34 41
44. J. El Khoury, M. Toft, S.E. Hickman, T.K. Means, K. Terada, C. Geula, and A.D. Luster Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease Nat. Med. 13 2007 432 438 10.1038/nm1555
45. J.B. El Khoury, K.J. Moore, T.K. Means, J. Leung, K. Terada, M. Toft, M.W. Freeman, and A.D. Luster CD36 mediates the innate host response to beta-amyloid J. Exp. Med. 197 2003 1657 1666 10.1084/jem.20021546
46. M.R.P. Elmore, A.R. Najafi, M.A. Koike, N.N. Dagher, E.E. Spangenberg, R.A. Rice, M. Kitazawa, B. Matusow, H. Nguyen, B.L. West, and K.N. Green Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain Neuron 82 2014 380 397 10.1016/j.neuron.2014.02.040
47. M. Emre Dementia associated with Parkinson's disease Lancet Neurol. 2 2003 229 237 10.1016/S1474-4422(03)00351-X
48. B. Engelhardt, and R.M. Ransohoff Capture, crawl, cross: the T cell code to breach the blood-brain barriers Trends Immunol. 33 2012 579 589 10.1016/j.it.2012.07.004
49. M. Erta, A. Quintana, and J. Hidalgo Interleukin-6, a major cytokine in the central nervous system Int. J. Biol. Sci. 8 2012 1254 1266 10.7150/ijbs.4679
50. L. Fellner, R. Irschick, K. Schanda, M. Reindl, L. Klimaschewski, W. Poewe, G.K. Wenning, and N. Stefanova Toll-like receptor 4 is required for α-synuclein dependent activation of microglia and astroglia Glia 61 2013 349 360 10.1002/glia.22437
51. C.E. Finch, N.J. Laping, T.E. Morgan, N.R. Nichols, and G.M. Pasinetti TGF-beta 1 is an organizer of responses to neurodegeneration J. Cell. Biochem. 53 1993 314 322 10.1002/jcb.240530408
52. D. Fishman, G. Faulds, R. Jeffery, V. Mohamed-Ali, J.S. Yudkin, S. Humphries, and P. Woo The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis J. Clin. Investig. 102 1998 1369 1376 10.1172/JCI2629
53. Flex, A., Giovannini, S., Biscetti, F., Liperoti, R., Spalletta, G., Straface, G., Landi, F., Angelini, F., Caltagirone, C., Ghirlanda, G., Bernabei, R., 2013. Effect of proinflammatory gene polymorphisms on the risk of Alzheimer's disease. Neurodegener. Dis. 10.1159/000353395
54. R.A. Floyd Antioxidants, oxidative stress, and degenerative neurological disorders Proc. Soc. Exp. Biol. Med. 222 1999 236 245
55. M.S. Forman, J.Q. Trojanowski, and V.M.-Y. Lee Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs Nat. Med. 10 2004 1055 1063 10.1038/nm1113
56. T.C. Frank-Cannon, T. Tran, K.A. Ruhn, T.N. Martinez, J. Hong, M. Marvin, M. Hartley, I. Treviño, D.E. O'Brien, B. Casey, M.S. Goldberg, and M.G. Tansey Parkin deficiency increases vulnerability to inflammation-related nigral degeneration J. Neurosci. 28 2008 10825 10834 10.1523/JNEUROSCI.3001-08.2008
57. S.A. Frautschy, G.M. Cole, and A. Baird Phagocytosis and deposition of vascular beta-amyloid in rat brains injected with Alzheimer beta-amyloid Am. J. Pathol. 140 1992 1389 1399
58. M. Gandelman, H. Peluffo, J.S. Beckman, P. Cassina, and L. Barbeito Extracellular ATP and the P2X7 receptor in astrocyte-mediated motor neuron death: implications for amyotrophic lateral sclerosis J. Neuroinflamm. 7 2010 33 10.1186/1742-2094-7-33
59. H.-M. Gao, H. Zhou, and J.-S. Hong NADPH oxidases: novel therapeutic targets for neurodegenerative diseases Trends Pharmacol. Sci. 33 2012 295 303 10.1016/j.tips.2012.03.008
60. A. Gardet, Y. Benita, C. Li, B.E. Sands, I. Ballester, C. Stevens, J.R. Korzenik, J.D. Rioux, M.J. Daly, R.J. Xavier, and D.K. Podolsky LRRK2 is involved in the IFN-gamma response and host response to pathogens J. Immunol. 185 2010 5577 5585 10.4049/jimmunol.1000548
61. F. Gillardon, R. Schmid, and H. Draheim Parkinson's disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity Neuroscience 208 2012 41 48 10.1016/j.neuroscience.2012.02.001
62. F. Ginhoux, M. Greter, M. Leboeuf, S. Nandi, P. See, S. Gokhan, M.F. Mehler, S.J. Conway, L.G. Ng, E.R. Stanley, I.M. Samokhvalov, and M. Merad Fate mapping analysis reveals that adult microglia derive from primitive macrophages Science 330 2010 841 845 10.1126/science.1194637
63. C.K. Glass, K. Saijo, B. Winner, M.C. Marchetto, and F.H. Gage Mechanisms underlying inflammation in neurodegeneration Cell 140 2010 918 934 10.1016/j.cell.2010.02.016
64. G. Gowing, F. Dequen, G. Soucy, and J.-P. Julien Absence of tumor necrosis factor-alpha does not affect motor neuron disease caused by superoxide dismutase 1 mutations J. Neurosci. 26 2006 11397 11402 10.1523/JNEUROSCI.0602-06.2006
65. M.C. Graves, M. Fiala, L.A. V Dinglasan, N.Q. Liu, J. Sayre, F. Chiappelli, C. van Kooten, and H.V. Vinters Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells Amyotroph. Lateral Scler. Other Motor Neuron Disord. 5 2004 213 219
66. A. Griciuc, A. Serrano-Pozo, A.R. Parrado, A.N. Lesinski, C.N. Asselin, K. Mullin, B. Hooli, S.H. Choi, B.T. Hyman, and R.E. Tanzi Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta Neuron 78 2013 631 643 10.1016/j.neuron.2013.04.014
67. X.-L. Gu, C.-X. Long, L. Sun, C. Xie, X. Lin, and H. Cai Astrocytic expression of Parkinson's disease-related A53T alpha-synuclein causes neurodegeneration in mice Mol. Brain 3 2010 12 10.1186/1756-6606-3-12
68. R. Guerreiro, A. Wojtas, J. Bras, M. Carrasquillo, E. Rogaeva, E. Majounie, C. Cruchaga, C. Sassi, J.S.K. Kauwe, S. Younkin, L. Hazrati, J. Collinge, J. Pocock, T. Lashley, J. Williams, J.-C. Lambert, P. Amouyel, A. Goate, R. Rademakers, K. Morgan, J. Powell St, P. George-Hyslop, A. Singleton, and J. Hardy TREM2 variants in Alzheimer's disease N. Engl. J. Med. 368 2013 117 127 10.1056/NEJMoa1211851
69. M.-V. Guillot-Sestier, and T. Town Innate immunity in Alzheimer's disease: a complex affair CNS Neurol. Disord. Drug Targets 12 2013 593 607
70. L. Guo, M.J. LaDu, and L.J. Van Eldik A dual role for apolipoprotein e in neuroinflammation: anti- and pro-inflammatory activity J. Mol. Neurosci. 23 2004 205 212 10.1385/JMN:23:3:205
71. M.E. Gurney, H. Pu, A.Y. Chiu, M.C. Dal Canto, C.Y. Polchow, D.D. Alexander, J. Caliendo, A. Hentati, Y.W. Kwon, and H.X. Deng Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation Science 264 1994 1772 1775
72. A. Halle, V. Hornung, G.C. Petzold, C.R. Stewart, B.G. Monks, T. Reinheckel, K.A. Fitzgerald, E. Latz, K.J. Moore, and D.T. Golenbock The NALP3 inflammasome is involved in the innate immune response to amyloid-beta Nat. Immunol. 9 2008 857 865 10.1038/ni.1636
73. G.M. Halliday, A. Ophof, M. Broe, P.H. Jensen, E. Kettle, H. Fedorow, M.I. Cartwright, F.M. Griffiths, C.E. Shepherd, and K.L. Double Alpha-synuclein redistributes to neuromelanin lipid in the substantia nigra early in Parkinson's disease Brain 128 2005 2654 2664 10.1093/brain/awh584
74. G.M. Halliday, and C.H. Stevens Glia: initiators and progressors of pathology in Parkinson's disease Mov. Disord. 26 2011 6 17 10.1002/mds.23455
75. T.H. Hamza, C.P. Zabetian, A. Tenesa, A. Laederach, J. Montimurro, D. Yearout, D.M. Kay, K.F. Doheny, J. Paschall, E. Pugh, V.I. Kusel, R. Collura, J. Roberts, A. Griffith, A. Samii, W.K. Scott, J. Nutt, S.A. Factor, and H. Payami Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease Nat. Genet. 42 2010 781 785 10.1038/ng.642
76. U.-K. Hanisch, and H. Kettenmann Microglia: active sensor and versatile effector cells in the normal and pathologic brain Nat. Neurosci. 10 2007 1387 1394 10.1038/nn1997
77. J. Hardy, and D. Allsop Amyloid deposition as the central event in the aetiology of Alzheimer's disease Trends Pharmacol. Sci. 12 1991 383 388
78. J. Hardy, and D.J. Selkoe The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics Science 297 2002 353 356 10.1126/science.1072994
79. C.A. Hawkes, and J. McLaurin Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy Proc. Natl. Acad. Sci. U. S. A. 106 2009 1261 1266 10.1073/pnas.0805453106
80. L.-N. Hazrati, C. Van Cauwenberghe, P.L. Brooks, N. Brouwers, M. Ghani, C. Sato, M. Cruts, K. Sleegers St, P. George-Hyslop, C. Van Broeckhoven, and E. Rogaeva Genetic association of CR1 with Alzheimer's disease: a tentative disease mechanism Neurobiol. Aging 33 12 2012 2949.e5 2949.e12
81. P. He, Z. Zhong, K. Lindholm, L. Berning, W. Lee, C. Lemere, M. Staufenbiel, R. Li, and Y. Shen Deletion of tumor necrosis factor death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer's mice J. Cell Biol. 178 2007 829 841 10.1083/jcb.200705042
82. M.T. Heneka, M.P. Kummer, A. Stutz, A. Delekate, S. Schwartz, A. Vieira-Saecker, A. Griep, D. Axt, A. Remus, T.-C. Tzeng, E. Gelpi, A. Halle, M. Korte, E. Latz, and D.T. Golenbock NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice Nature 493 2012 674 678 10.1038/nature11729
83. J.S. Henkel, D.R. Beers, L. Siklós, and S.H. Appel The chemokine MCP-1 and the dendritic and myeloid cells it attracts are increased in the mSOD1 mouse model of ALS Mol. Cell. Neurosci. 31 2006 427 437 10.1016/j.mcn.2005.10.016
84. J.S. Henkel, D.R. Beers, S. Wen, A.L. Rivera, K.M. Toennis, J.E. Appel, W. Zhao, D.H. Moore, S.Z. Powell, and S.H. Appel Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival EMBO Mol. Med. 5 2013 64 79 10.1002/emmm.201201544
85. E.C. Hirsch, and S. Hunot Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol. 8 2009 382 397 10.1016/S1474-4422(09)70062-6
86. E.C. Hirsch, S. Vyas, and S. Hunot Neuroinflammation in Parkinson's disease Parkinsonism Relat. Disord. 18 Suppl 1 2012 S210 S212 10.1016/S1353-8020(11)70065-7
87. P. Holmans, V. Moskvina, L. Jones, M. Sharma, A. Vedernikov, F. Buchel, M. Saad, M. Sadd, J.M. Bras, F. Bettella, N. Nicolaou, J. Simón-Sánchez, F. Mittag, J.R. Gibbs, C. Schulte, A. Durr, R. Guerreiro, D. Hernandez, A. Brice, H. Stefánsson, K. Majamaa, T. Gasser, P. Heutink, N.W. Wood, M. Martinez, A.B. Singleton, M.A. Nalls, J. Hardy, H.R. Morris, and N.M. Williams A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease Hum. Mol. Genet. 22 2013 1039 1049 10.1093/hmg/dds492
88. C. Huang, J. Tong, F. Bi, H. Zhou, and X.-G. Xia Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats J. Clin. Investig. 122 2012 107 118 10.1172/JCI59130
89. S. Hunot, F. Boissière, B. Faucheux, B. Brugg, A. Mouatt-Prigent, Y. Agid, and E.C. Hirsch Nitric oxide synthase and neuronal vulnerability in Parkinson's disease Neuroscience 72 1996 355 363
90. S. Hunot, B. Brugg, D. Ricard, P.P. Michel, M.P. Muriel, M. Ruberg, B.A. Faucheux, Y. Agid, and E.C. Hirsch Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with parkinson disease Proc. Natl. Acad. Sci. U. S. A 94 1997 7531 7536
91. H. Ilieva, M. Polymenidou, and D.W. Cleveland Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond J. Cell Biol. 187 2009 761 772 10.1083/jcb.200908164
92. K. Imamura, N. Hishikawa, M. Sawada, T. Nagatsu, M. Yoshida, and Y. Hashizume Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains Acta Neuropathol. 106 2003 518 526 10.1007/s00401-003-0766-2
93. B.A. in t' Veld, A. Ruitenberg, A. Hofman, L.J. Launer, C.M. van Duijn, T. Stijnen, M.M. Breteler, and B.H. Stricker Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease N. Engl. J. Med. 345 2001 1515 1521 10.1056/NEJMoa010178
94. N.G. Innamorato, A. Jazwa, A.I. Rojo, C. García, J. Fernández-Ruiz, A. Grochot-Przeczek, A. Stachurska, A. Jozkowicz, J. Dulak, and A. Cuadrado Different susceptibility to the Parkinson's toxin MPTP in mice lacking the redox master regulator Nrf2 or its target gene heme oxygenase-1 PLoS One 5 2010 e11838 10.1371/journal.pone.0011838
95. Y. Ishida, A. Nagai, S. Kobayashi, and S.U. Kim Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease: astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase J. Neuropathol. Exp. Neurol. 65 2006 66 77
96. R.J. Jakel, J.A. Townsend, A.D. Kraft, and J.A. Johnson Nrf2-mediated protection against 6-hydroxydopamine Brain Res. 1144 2007 192 201 10.1016/j.brainres.2007.01.131
97. T. Jiang, J.-T. Yu, X.-C. Zhu, and L. Tan TREM2 in Alzheimer's disease Mol. Neurobiol. 48 2013 180 185 10.1007/s12035-013-8424-8
98. T. Jonsson, H. Stefansson, S. Steinberg, I. Jonsdottir, P. V Jonsson, J. Snaedal, S. Bjornsson, J. Huttenlocher, A.I. Levey, J.J. Lah, D. Rujescu, H. Hampel, I. Giegling, O.A. Andreassen, K. Engedal, I. Ulstein, S. Djurovic, C. Ibrahim-Verbaas, A. Hofman, M.A. Ikram, C.M. van Duijn, U. Thorsteinsdottir, A. Kong, and K. Stefansson Variant of TREM2 associated with the risk of Alzheimer's disease N. Engl. J. Med. 368 2013 107 116 10.1056/NEJMoa1211103
99. E. Kabashi, P.N. Valdmanis, P. Dion, D. Spiegelman, B.J. McConkey, C. Vande Velde, J.-P. Bouchard, L. Lacomblez, K. Pochigaeva, F. Salachas, P.-F. Pradat, W. Camu, V. Meininger, N. Dupre, and G.A. Rouleau TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis Nat. Genet. 40 2008 572 574 10.1038/ng.132
100. A. Kastner, E.C. Hirsch, O. Lejeune, F. Javoy-Agid, O. Rascol, and Y. Agid Is the vulnerability of neurons in the substantia nigra of patients with Parkinson's disease related to their neuromelanin content? J. Neurochem. 59 1992 1080 1089
101. T. Kawai, and S. Akira The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors Nat. Immunol. 11 2010 373 384 10.1038/ni.1863
102. T. Kawai, and S. Akira Toll-like receptors and their crosstalk with other innate receptors in infection and immunity Immunity 34 2011 637 650 10.1016/j.immuni.2011.05.006
103. P.J. Khandelwal, A.M. Herman, and C.E.-H. Moussa Inflammation in the early stages of neurodegenerative pathology J. Neuroimmunol. 238 2011 1 11 10.1016/j.jneuroim.2011.07.002
104. C. Kim, D.-H. Ho, J.-E. Suk, S. You, S. Michael, J. Kang, S. Joong Lee, E. Masliah, D. Hwang, H.-J. Lee, and S.-J. Lee Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia Nat. Commun. 4 2013 1562 10.1038/ncomms2534
105. J. Kim, J.M. Basak, and D.M. Holtzman The role of apolipoprotein E in Alzheimer's disease Neuron 63 2009 287 303 10.1016/j.neuron.2009.06.026
106. Y.S. Kim, D.H. Choi, M.L. Block, S. Lorenzl, L. Yang, Y.J. Kim, S. Sugama, B.P. Cho, O. Hwang, S.E. Browne, S.Y. Kim, J.-S. Hong, M.F. Beal, and T.H. Joh A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activation FASEB J. 21 2007 179 187 10.1096/fj.06-5865com
107. J. Kipnis, H. Cohen, M. Cardon, Y. Ziv, and M. Schwartz T cell deficiency leads to cognitive dysfunction: implications for therapeutic vaccination for schizophrenia and other psychiatric conditions Proc. Natl. Acad. Sci. U. S. A 101 2004 8180 8185 10.1073/pnas.0402268101
108. A. Klegeris, S. Pelech, B.I. Giasson, J. Maguire, H. Zhang, E.G. McGeer, and P.L. McGeer Alpha-synuclein activates stress signaling protein kinases in THP-1 cells and microglia Neurobiol. Aging 29 2008 739 752 10.1016/j.neurobiolaging.2006.11.013
109. C. Knott, G. Stern, and G.P. Wilkin Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2 Mol. Cell. Neurosci. 16 2000 724 739 10.1006/mcne.2000.0914
110. J. Kuhle, R.L.P. Lindberg, A. Regeniter, M. Mehling, A.J. Steck, L. Kappos, and A. Czaplinski Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis Eur. J. Neurol. 16 2009 771 774 10.1111/j.1468-1331.2009.02560.x
111. H. Kumar, S. Koppula, I.-S. Kim, S.V. More, B.-W. Kim, and D.-K. Choi Nuclear factor erythroid 2-related factor 2 signaling in Parkinson disease: a promising multi therapeutic target against oxidative stress, neuroinflammation and cell death CNS Neurol. Disord. Drug Targets 11 2012 1015 1029
112. T.J. Kwiatkowski, D.A. Bosco, A.L. Leclerc, E. Tamrazian, C.R. Vanderburg, C. Russ, A. Davis, J. Gilchrist, E.J. Kasarskis, T. Munsat, P. Valdmanis, G.A. Rouleau, B.A. Hosler, P. Cortelli, P.J. de Jong, Y. Yoshinaga, J.L. Haines, M.A. Pericak-Vance, J. Yan, N. Ticozzi, T. Siddique, D. McKenna-Yasek, P.C. Sapp, H.R. Horvitz, J.E. Landers, and R.H. Brown Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis Science 323 2009 1205 1208 10.1126/science.1166066
113. A. Lampron, P.M. Pimentel-Coelho, and S. Rivest Migration of bone marrow-derived cells into the central nervous system in models of neurodegeneration J. Comp. Neurol. 521 2013 3863 3876 10.1002/cne.23363
114. L.J. Lawson, V.H. Perry, P. Dri, and S. Gordon Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain Neuroscience 39 1990 151 170
115. M.D. Ledesma, C. Galvan, B. Hellias, C. Dotti, and P.H. Jensen Astrocytic but not neuronal increased expression and redistribution of parkin during unfolded protein stress J. Neurochem. 83 2002 1431 1440
116. H.-J. Lee, J.-E. Suk, C. Patrick, E.-J. Bae, J.-H. Cho, S. Rho, D. Hwang, E. Masliah, and S.-J. Lee Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies J. Biol. Chem. 285 2010 9262 9272 10.1074/jbc.M109.081125
117. M. Letiembre, Y. Liu, S. Walter, W. Hao, T. Pfander, A. Wrede, W. Schulz-Schaeffer, and K. Fassbender Screening of innate immune receptors in neurodegenerative diseases: a similar pattern Neurobiol. Aging 30 2009 759 768 10.1016/j.neurobiolaging.2007.08.018
118. C.-A. Lewis, J. Manning, F. Rossi, and C. Krieger The neuroinflammatory response in ALS: the roles of microglia and T cells Neurol. Res. Int. 2012 2012 803701 10.1155/2012/803701
119. B. Liao, W. Zhao, D.R. Beers, J.S. Henkel, and S.H. Appel Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS Exp. Neurol. 237 2012 147 152 10.1016/j.expneurol.2012.06.011
120. R.S. Liblau, D. Gonzalez-Dunia, H. Wiendl, and F. Zipp Neurons as targets for T cells in the nervous system Trends Neurosci. 36 2013 315 324 10.1016/j.tins.2013.01.008
121. L.F. Lin, D.H. Doherty, J.D. Lile, S. Bektesh, and F. Collins GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons Science 260 1993 1130 1132
122. S.-C. Ling, M. Polymenidou, and D.W. Cleveland Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis Neuron 79 2013 416 438 10.1016/j.neuron.2013.07.033
123. C.F. Lippa, H. Fujiwara, D.M. Mann, B. Giasson, M. Baba, M.L. Schmidt, L.E. Nee, B. O'Connell, D.A. Pollen, P. St George-Hyslop, B. Ghetti, D. Nochlin, T.D. Bird, N.J. Cairns, V.M. Lee, T. Iwatsubo, and J.Q. Trojanowski Lewy bodies contain altered alpha-synuclein in brains of many familial Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes Am. J. Pathol. 153 1998 1365 1370
124. J. Lipski, R. Nistico, N. Berretta, E. Guatteo, G. Bernardi, and N.B. Mercuri L-DOPA: a scapegoat for accelerated neurodegeneration in Parkinson's disease? Prog. Neurobiol. 94 2011 389 407 10.1016/j.pneurobio.2011.06.005
125. B. Liu Modulation of microglial pro-inflammatory and neurotoxic activity for the treatment of Parkinson's disease AAPS J. 8 2006 E606 E621 10.1208/aapsj080369
126. Y. Liu, W. Hao, A. Dawson, S. Liu, and K. Fassbender Expression of amyotrophic lateral sclerosis-linked SOD1 mutant increases the neurotoxic potential of microglia via TLR2 J. Biol. Chem. 284 2009 3691 3699 10.1074/jbc.M804446200
127. C.M. Long-Smith, A.M. Sullivan, and Y.M. Nolan The influence of microglia on the pathogenesis of Parkinson's disease Prog. Neurobiol. 89 2009 277 287 10.1016/j.pneurobio.2009.08.001
128. S.-M. Lucas, N.J. Rothwell, and R.M. Gibson The role of inflammation in CNS injury and disease Br. J. Pharmacol. 147 Suppl 2006 S232 S240 10.1038/sj.bjp.0706400
129. S.L. Ma, N.L.S. Tang, L.C.W. Lam, and H.F.K. Chiu Association between tumor necrosis factor-alpha promoter polymorphism and Alzheimer's disease Neurology 62 2004 307 309
130. A. Majumdar, D. Cruz, N. Asamoah, A. Buxbaum, I. Sohar, P. Lobel, and F.R. Maxfield Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils Mol. Biol. Cell 18 2007 1490 1496 10.1091/mbc.E06-10-0975
131. I. Martin, V.L. Dawson, and T.M. Dawson Recent advances in the genetics of Parkinson's disease Annu. Rev. Genomics Hum. Genet. 12 2011 301 325 10.1146/annurev-genom-082410-101440
132. H. McCann, C.H. Stevens, H. Cartwright, and G.M. Halliday α-Synucleinopathy phenotypes Parkinsonism Relat. Disord. 20 Suppl 1 2014 S62 S67 10.1016/S1353-8020(13)70017-8
133. P.L. McGeer, S. Itagaki, B.E. Boyes, and E.G. McGeer Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains Neurology 38 1988 1285 1291
134. P.L. McGeer, and E.G. McGeer Inflammatory processes in amyotrophic lateral sclerosis Muscle Nerve 26 2002 459 470 10.1002/mus.10191
135. P.L. McGeer, and E.G. McGeer NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies Neurobiol. Aging 28 2007 639 647 10.1016/j.neurobiolaging.2006.03.013
136. S.O. McGuire, Z.D. Ling, J.W. Lipton, C.E. Sortwell, T.J. Collier, and P.M. Carvey Tumor necrosis factor alpha is toxic to embryonic mesencephalic dopamine neurons Exp. Neurol. 169 2001 219 230 10.1006/exnr.2001.7688
137. F. Meissner, K. Molawi, and A. Zychlinsky Mutant superoxide dismutase 1-induced IL-1beta accelerates ALS pathogenesis Proc. Natl. Acad. Sci. U. S. A 107 2010 13046 13050 10.1073/pnas.1002396107
138. J.-P. Michaud, M.-A. Bellavance, P. Préfontaine, and S. Rivest Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta Cell Rep. 5 2013 646 653 10.1016/j.celrep.2013.10.010
139. J.-P. Michaud, M. Hallé, A. Lampron, P. Thériault, P. Préfontaine, M. Filali, P. Tribout-Jover, A.-M. Lanteigne, R. Jodoin, C. Cluff, V. Brichard, R. Palmantier, A. Pilorget, D. Larocque, and S. Rivest Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer's disease-related pathology Proc. Natl. Acad. Sci. U. S. A 110 2013 1941 1946 10.1073/pnas.1215165110
140. J. Miklossy, T. Arai, J.-P. Guo, A. Klegeris, S. Yu, E.G. McGeer, and P.L. McGeer LRRK2 expression in normal and pathologic human brain and in human cell lines J. Neuropathol. Exp. Neurol. 65 2006 953 963 10.1097/01.jnen.0000235121.98052.54
141. J. Miklossy, D.D. Doudet, C. Schwab, S. Yu, E.G. McGeer, and P.L. McGeer Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys Exp. Neurol. 197 2006 275 283 10.1016/j.expneurol.2005.10.034
142. P. Minoretti, C. Gazzaruso, C. Vito, E. Di, Emanuele, M. Bianchi, E. Coen, M. Reino, and D. Geroldi Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer's disease Neurosci. Lett. 391 2006 147 149 10.1016/j.neulet.2005.08.047
143. B. Mirza, H. Hadberg, P. Thomsen, and T. Moos The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson's disease Neuroscience 95 2000 425 432
144. M. Mizutani, P.A. Pino, N. Saederup, I.F. Charo, R.M. Ransohoff, and A.E. Cardona The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood J. Immunol. 188 2012 29 36 10.4049/jimmunol.1100421
145. M.S. Moehle, P.J. Webber, T. Tse, N. Sukar, D.G. Standaert, T.M. DeSilva, R.M. Cowell, and A.B. West LRRK2 inhibition attenuates microglial inflammatory responses J. Neurosci. 32 2012 1602 1611 10.1523/JNEUROSCI.5601-11.2012
146. M. Mogi, M. Harada, T. Kondo, P. Riederer, H. Inagaki, M. Minami, and T. Nagatsu Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients Neurosci. Lett. 180 1994 147 150
147. M. Mogi, M. Harada, P. Riederer, H. Narabayashi, K. Fujita, and T. Nagatsu Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients Neurosci. Lett. 165 1994 208 210
148. M. Mogi, M. Harada, T. Kondo, H. Narabayashi, P. Riederer, and T. Nagatsu Transforming growth factor-beta 1 levels are elevated in the striatum and in ventricular cerebrospinal fluid in Parkinson's disease Neurosci. Lett. 193 1995 129 132
149. M. Mogi, M. Harada, H. Narabayashi, H. Inagaki, M. Minami, and T. Nagatsu Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease Neurosci. Lett. 211 1996 13 16
150. M. Mogi, T. Kondo, Y. Mizuno, and T. Nagatsu p53 protein, interferon-gamma, and NF-kappaB levels are elevated in the parkinsonian brain Neurosci. Lett. 414 2007 94 97 10.1016/j.neulet.2006.12.003
151. D.J. Moore, A.B. West, V.L. Dawson, and T.M. Dawson Molecular pathophysiology of Parkinson's disease Annu. Rev. Neurosci. 28 2005 57 87 10.1146/annurev.neuro.28.061604.135718
152. T. Mori, N. Koyama, G.W. Arendash, Y. Horikoshi-Sakuraba, J. Tan, and T. Town Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease Glia 58 2010 300 314 10.1002/glia.20924
153. S.J. Mullett, R.L. Hamilton, and D.A. Hinkle DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age Neuropathology 29 2009 125 131 10.1111/j.1440-1789.2008.00955.x
154. G. Naert, and S. Rivest CC chemokine receptor 2 deficiency aggravates cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer's disease J. Neurosci. 31 2011 6208 6220 10.1523/JNEUROSCI.0299-11.2011
155. G. Naert, and S. Rivest A deficiency in CCR2+ monocytes: the hidden side of Alzheimer's disease J. Mol. Cell Biol. 5 2013 284 293 10.1093/jmcb/mjt028
156. T. Nagatsu, M. Mogi, H. Ichinose, and A. Togari Cytokines in Parkinson's disease J. Neural Transm. Suppl. 58 2000 143 151
157. K. Newton, and V.M. Dixit Signaling in innate immunity and inflammation Cold Spring Harb. Perspect. Biol. 4 2012 a006049 10.1101/cshperspect.a006049
158. A. Nimmerjahn, F. Kirchhoff, and F. Helmchen Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo Science 308 2005 1314 1318 10.1126/science.1110647
159. C. Noelker, L. Morel, T. Lescot, A. Osterloh, D. Alvarez-Fischer, M. Breloer, C. Henze, C. Depboylu, D. Skrzydelski, P.P. Michel, R.C. Dodel, L. Lu, E.C. Hirsch, S. Hunot, and A. Hartmann Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease Sci. Rep. 3 2013 1393 10.1038/srep01393
160. C.F. Orr, D.B. Rowe, Y. Mizuno, H. Mori, and G.M. Halliday A possible role for humoral immunity in the pathogenesis of Parkinson's disease Brain 128 2005 2665 2674 10.1093/brain/awh625
161. M.A. Panaro, D.D. Lofrumento, C. Saponaro, F. De Nuccio, A. Cianciulli, V. Mitolo, and G. Nicolardi Expression of TLR4 and CD14 in the central nervous system (CNS) in a MPTP mouse model of Parkinson's-like disease Immunopharmacol. Immunotoxicol. 30 2008 729 740 10.1080/08923970802278557
162. Prokop, S., Miller, K.R., Heppner, F.L., 2013. Microglia actions in Alzheimer's disease. Acta Neuropathol. 10.1007/s00401-013-1182-x
163. E.M. Ramos, M.-T. Lin, E.B. Larson, I. Maezawa, L.-H. Tseng, K.L. Edwards, G.D. Schellenberg, J.A. Hansen, W.A. Kukull, and L.-W. Jin Tumor necrosis factor alpha and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease Arch. Neurol. 63 2006 1165 1169 10.1001/archneur.63.8.1165
164. R.M. Ransohoff, and A.E. Cardona The myeloid cells of the central nervous system parenchyma Nature 468 2010 253 262 10.1038/nature09615
165. R.M. Ransohoff, and M.A. Brown Innate immunity in the central nervous system J. Clin. Investig. 122 2012 1164 1171 10.1172/JCI58644
166. R.M. Ransohoff, and B. Engelhardt The anatomical and cellular basis of immune surveillance in the central nervous system Nat. Rev. Immunol. 12 2012 623 635 10.1038/nri3265
167. C. Raoul, E. Buhler, C. Sadeghi, A. Jacquier, P. Aebischer, B. Pettmann, C.E. Henderson, and G. Haase Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of a feedback loop involving Fas, Daxx, and FasL Proc. Natl. Acad. Sci. U. S. A 103 2006 6007 6012 10.1073/pnas.0508774103
168. C. Raoul, A.G. Estévez, H. Nishimune, D.W. Cleveland, O. deLapeyrière, C.E. Henderson, G. Haase, and B. Pettmann Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations Neuron 35 2002 1067 1083
169. E.G. Reed-Geaghan, J.C. Savage, A.G. Hise, and G.E. Landreth CD14 and toll-like receptors 2 and 4 are required for fibrillar A{beta}-stimulated microglial activation J. Neurosci. 29 2009 11982 11992 10.1523/JNEUROSCI.3158-09.2009
170. A.E. Renton, A. Chiò, and B.J. Traynor State of play in amyotrophic lateral sclerosis genetics Nat. Neurosci. 17 2014 17 23 10.1038/nn.3584
171. A.E. Renton, E. Majounie, A. Waite, J. Simón-Sánchez, S. Rollinson, J.R. Gibbs, J.C. Schymick, H. Laaksovirta, J.C. van Swieten, L. Myllykangas, H. Kalimo, A. Paetau, Y. Abramzon, A.M. Remes, A. Kaganovich, S.W. Scholz, J. Duckworth, J. Ding, D.W. Harmer, D.G. Hernandez, J.O. Johnson, K. Mok, M. Ryten, D. Trabzuni, R.J. Guerreiro, R.W. Orrell, J. Neal, A. Murray, J. Pearson, I.E. Jansen, D. Sondervan, H. Seelaar, D. Blake, K. Young, N. Halliwell, J.B. Callister, G. Toulson, A. Richardson, A. Gerhard, J. Snowden, D. Mann, D. Neary, M.A. Nalls, T. Peuralinna, L. Jansson, V.-M. Isoviita, A.-L. Kaivorinne, M. Hölttä-Vuori, E. Ikonen, R. Sulkava, M. Benatar, J. Wuu, A. Chiò, G. Restagno, G. Borghero, M. Sabatelli, D. Heckerman, E. Rogaeva, L. Zinman, J.D. Rothstein, M. Sendtner, C. Drepper, E.E. Eichler, C. Alkan, Z. Abdullaev, S.D. Pack, A. Dutra, E. Pak, J. Hardy, A. Singleton, N.M. Williams, P. Heutink, S. Pickering-Brown, H.R. Morris, P.J. Tienari, and B.J. Traynor A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD Neuron 72 2011 257 268 10.1016/j.neuron.2011.09.010
172. M. Rentzos, E. Evangelopoulos, E. Sereti, V. Zouvelou, S. Marmara, T. Alexakis, and I. Evdokimidis Alterations of T cell subsets in ALS: a systemic immune activation? Acta Neurol. Scand. 125 2012 260 264 10.1111/j.1600-0404.2011.01528.x
173. D.R. Rosen, T. Siddique, D. Patterson, D.A. Figlewicz, P. Sapp, A. Hentati, D. Donaldson, J. Goto, J.P. O'Regan, and H.X. Deng Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis Nature 362 1993 59 62 10.1038/362059a0
174. ADAPT Results of a follow-up study to the randomized Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) Alzheimers Dement. 9 2013 714 723 10.1016/j.jalz.2012.11.012
175. N. Rothwell Interleukin 1 in the brain: biology, pathology and therapeutic target Trends Neurosci. 23 2000 618 625 10.1016/S0166-2236(00)01661-1
176. P. Salins, Y. He, K. Olson, G. Glazner, T. Kashour, and F. Amara TGF-beta1 is increased in a transgenic mouse model of familial Alzheimer's disease and causes neuronal apoptosis Neurosci. Lett. 430 2008 81 86 10.1016/j.neulet.2007.10.025
177. M.W. Salter, and S. Beggs Sublime microglia: expanding roles for the guardians of the CNS Cell 158 2014 15 24 10.1016/j.cell.2014.06.008
178. M. Sandberg, J. Patil, B. D'Angelo, S.G. Weber, and C. Mallard NRF2-regulation in brain health and disease: implication of cerebral inflammation Neuropharmacology 79C 2014 298 306 10.1016/j.neuropharm.2013.11.004
179. S.A. Sargsyan, P.N. Monk, and P.J. Shaw Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis Glia 51 2005 241 253 10.1002/glia.20210
180. D.P. Schafer, E.K. Lehrman, A.G. Kautzman, R. Koyama, A.R. Mardinly, R. Yamasaki, R.M. Ransohoff, M.E. Greenberg, B.A. Barres, and B. Stevens Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner Neuron 74 2012 691 705 10.1016/j.neuron.2012.03.026
181. M. Schwartz, J. Kipnis, S. Rivest, and A. Prat How do immune cells support and shape the brain in health, disease, and aging? J. Neurosci. 33 2013 17587 17596 10.1523/JNEUROSCI.3241-13.2013
182. R. Shechter, A. London, C. Varol, C. Raposo, M. Cusimano, G. Yovel, A. Rolls, M. Mack, S. Pluchino, G. Martino, S. Jung, and M. Schwartz Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice PLoS Med. 6 2009 e1000113 10.1371/journal.pmed.1000113
183. K. Shimada, T.R. Crother, J. Karlin, J. Dagvadorj, N. Chiba, S. Chen, V.K. Ramanujan, A.J. Wolf, L. Vergnes, D.M. Ojcius, A. Rentsendorj, M. Vargas, C. Guerrero, Y. Wang, K.A. Fitzgerald, D.M. Underhill, T. Town, and M. Arditi Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis Immunity 36 2012 401 414 10.1016/j.immuni.2012.01.009
184. H. Shimizu, Y. Toyoshima, A. Shiga, A. Yokoseki, K. Arakawa, Y. Sekine, T. Shimohata, T. Ikeuchi, M. Nishizawa, A. Kakita, O. Onodera, and H. Takahashi Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene Acta Neuropathol. 126 2013 453 459 10.1007/s00401-013-1150-5
185. A.R. Simard, D. Soulet, G. Gowing, J.-P. Julien, and S. Rivest Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease Neuron 49 2006 489 502 10.1016/j.neuron.2006.01.022
186. M. V Sofroniew, and H. V Vinters Astrocytes: biology and pathology Acta Neuropathol. 119 2010 7 35 10.1007/s00401-009-0619-8
187. A. Spooren, K. Kolmus, G. Laureys, R. Clinckers, J. De Keyser, G. Haegeman, and S. Gerlo Interleukin-6, a mental cytokine Brain Res. Rev. 67 2011 157 183 10.1016/j.brainresrev.2011.01.002
188. J. Sreedharan, I.P. Blair, V.B. Tripathi, X. Hu, C. Vance, B. Rogelj, S. Ackerley, J.C. Durnall, K.L. Williams, E. Buratti, F. Baralle, J. de Belleroche, J.D. Mitchell, P.N. Leigh, A. Al-Chalabi, C.C. Miller, G. Nicholson, and C.E. Shaw TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis Science 319 2008 1668 1672 10.1126/science.1154584
189. B.S. Srinivasan, J. Doostzadeh, F. Absalan, S. Mohandessi, R. Jalili, S. Bigdeli, J. Wang, J. Mahadevan, C.L.G. Lee, R.W. Davis, J. William Langston, and M. Ronaghi Whole genome survey of coding SNPs reveals a reproducible pathway determinant of Parkinson disease Hum. Mutat. 30 2009 228 238 10.1002/humu.20840
190. N. Stefanova, L. Fellner, M. Reindl, E. Masliah, W. Poewe, and G.K. Wenning Toll-like receptor 4 promotes α-synuclein clearance and survival of nigral dopaminergic neurons Am. J. Pathol. 179 2011 954 963 10.1016/j.ajpath.2011.04.013
191. B. Stevens, N.J. Allen, L.E. Vazquez, G.R. Howell, K.S. Christopherson, N. Nouri, K.D. Micheva, A.K. Mehalow, A.D. Huberman, B. Stafford, A. Sher, A.M. Litke, J.D. Lambris, S.J. Smith, S.W.M. John, and B.A. Barres The classical complement cascade mediates CNS synapse elimination Cell 131 2007 1164 1178 10.1016/j.cell.2007.10.036
192. V. Swarup, D. Phaneuf, N. Dupré, S. Petri, M. Strong, J. Kriz, and J.-P. Julien Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB-mediated pathogenic pathways J. Exp. Med. 208 2011 2429 2447 10.1084/jem.20111313
193. C.A. Szekely, and P.P. Zandi Non-steroidal anti-inflammatory drugs and Alzheimer's disease: the epidemiological evidence CNS Neurol. Disord. Drug Targets 9 2010 132 139
194. O. Takeuchi, and S. Akira Pattern recognition receptors and inflammation Cell 140 2010 805 820 10.1016/j.cell.2010.01.022
195. J. Tan, T. Town, M. Saxe, D. Paris, Y. Wu, and M. Mullan Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10 J. Immunol. 163 1999 6614 6621
196. K. Tanji, A. Maruyama, S. Odagiri, F. Mori, K. Itoh, A. Kakita, H. Takahashi, and K. Wakabayashi Keap1 is localized in neuronal and glial cytoplasmic inclusions in various neurodegenerative diseases J. Neuropathol. Exp. Neurol. 72 2013 18 28 10.1097/NEN.0b013e31827b5713
197. P. Teismann, K. Tieu, D.-K. Choi, D.-C. Wu, A. Naini, S. Hunot, M. Vila, V. Jackson-Lewis, and S. Przedborski Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration Proc. Natl. Acad. Sci. U. S. A 100 2003 5473 5478 10.1073/pnas.0837397100
198. I. Tesseur, K. Zou, L. Esposito, F. Bard, E. Berber, J. Can, A.H. Van, Lin, L. Crews, P. Tremblay, P. Mathews, L. Mucke, E. Masliah, and T. Wyss-Coray Deficiency in neuronal TGF-beta signaling promotes neurodegeneration and Alzheimer's pathology J. Clin. Investig. 116 2006 3060 3069 10.1172/JCI27341
199. E. Teyssou, T. Takeda, V. Lebon, S. Boillée, B. Doukouré, G. Bataillon, V. Sazdovitch, C. Cazeneuve, V. Meininger, E. LeGuern, F. Salachas, D. Seilhean, and S. Millecamps Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology Acta Neuropathol. 125 2013 511 522 10.1007/s00401-013-1090-0
200. T. Town, J. Tan, R.A. Flavell, and M. Mullan T-cells in Alzheimer's disease Neuromolecular Med. 7 2005 255 264 10.1385/NMM:7:3:255
201. T. Town, Y. Laouar, C. Pittenger, T. Mori, C.A. Szekely, J. Tan, R.S. Duman, and R.A. Flavell Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology Nat. Med. 14 2008 681 687 10.1038/nm1781
202. T.A. Tran, A.D. Nguyen, J. Chang, M.S. Goldberg, J.-K. Lee, and M.G. Tansey Lipopolysaccharide and tumor necrosis factor regulate Parkin expression via nuclear factor-kappa B PLoS One 6 2011 e23660 10.1371/journal.pone.0023660
203. J. Trinh, and M. Farrer Advances in the genetics of Parkinson disease Nat. Rev. Neurol. 9 2013 445 454 10.1038/nrneurol.2013.132
204. W. Tsao, Y.H. Jeong, S. Lin, J. Ling, D.L. Price, P.-M. Chiang, and P.C. Wong Rodent models of TDP-43: recent advances Brain Res. 1462 2012 26 39 10.1016/j.brainres.2012.04.031
205. K.U. Tufekci, S. Genc, and K. Genc The endotoxin-induced neuroinflammation model of Parkinson's disease Parkinsons Dis. 2011 2011 487450 10.4061/2011/487450
206. S. Uematsu, and S. Akira Toll-like receptors (TLRs) and their ligands Handb. Exp. Pharmacol. 2008 1 20 10.1007/978-3-540-72167-3-1
207. V.M. Van Deerlin, J.B. Leverenz, L.M. Bekris, T.D. Bird, W. Yuan, L.B. Elman, D. Clay, E.M. Wood, A.S. Chen-Plotkin, M. Martinez-Lage, E. Steinbart, L. McCluskey, M. Grossman, M. Neumann, I.-L. Wu, W.-S. Yang, R. Kalb, D.R. Galasko, T.J. Montine, J.Q. Trojanowski, V.M.-Y. Lee, G.D. Schellenberg, and C.-E. Yu TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis Lancet Neurol. 7 2008 409 416 10.1016/S1474-4422(08)70071-1
208. E.A. Van der Wal, F. Gómez-Pinilla, and C.W. Cotman Transforming growth factor-beta 1 is in plaques in Alzheimer and Down pathologies Neuroreport 4 1993 69 72
209. C. Vance, B. Rogelj, T. Hortobágyi, K.J. De Vos, A.L. Nishimura, J. Sreedharan, X. Hu, B. Smith, D. Ruddy, P. Wright, J. Ganesalingam, K.L. Williams, V. Tripathi, S. Al-Saraj, A. Al-Chalabi, P.N. Leigh, I.P. Blair, G. Nicholson, J. de Belleroche, J.-M. Gallo, C.C. Miller, and C.E. Shaw Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6 Science 323 2009 1208 1211 10.1126/science.1165942
210. M. Varçin, E. Bentea, Y. Michotte, and S. Sarre Oxidative stress in genetic mouse models of Parkinson's disease Oxid. Med. Cell. Longev. 2012 2012 624925 10.1155/2012/624925
211. J. Vom Berg, S. Prokop, K.R. Miller, J. Obst, R.E. Kälin, I. Lopategui-Cabezas, A. Wegner, F. Mair, C.G. Schipke, O. Peters, Y. Winter, B. Becher, and F.L. Heppner Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline Nat. Med. 18 2012 1812 1819 10.1038/nm.2965
212. J. Waak, S.S. Weber, A. Waldenmaier, K. Görner, M. Alunni-Fabbroni, H. Schell, D. Vogt-Weisenhorn, T.-T. Pham, V. Reumers, V. Baekelandt, W. Wurst, and P.J. Kahle Regulation of astrocyte inflammatory responses by the Parkinson's disease-associated gene DJ-1 FASEB J. 23 2009 2478 2489 10.1096/fj.08-125153
213. A.D. Wahner, J.S. Sinsheimer, J.M. Bronstein, and B. Ritz Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease Arch. Neurol. 64 2007 836 840 10.1001/archneur.64.6.836
214. H. Wake, A.J. Moorhouse, S. Jinno, S. Kohsaka, and J. Nabekura Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals J. Neurosci. 29 2009 3974 3980 10.1523/JNEUROSCI.4363-08.2009
215. L.-Z. Wang, J.-T. Yu, D. Miao, Z.-C. Wu, Y. Zong, C.-Q. Wen, and L. Tan Genetic association of TLR4/11367 polymorphism with late-onset Alzheimer's disease in a Han Chinese population Brain Res. 1381 2011 202 207 10.1016/j.brainres.2011.01.007
216. M.B. Watson, F. Richter, S.K. Lee, L. Gabby, J. Wu, E. Masliah, R.B. Effros, and M.-F. Chesselet Regionally-specific microglial activation in young mice over-expressing human wildtype alpha-synuclein Exp. Neurol. 237 2012 318 334 10.1016/j.expneurol.2012.06.025
217. I. Wegorzewska, S. Bell, N.J. Cairns, T.M. Miller, and R.H. Baloh TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration Proc. Natl. Acad. Sci. U. S. A 106 2009 18809 18814 10.1073/pnas.0908767106
218. H. Wilms, P. Rosenstiel, J. Sievers, G. Deuschl, L. Zecca, and R. Lucius Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson's disease FASEB J. 17 2003 500 502 10.1096/fj.02-0314fje
219. H. Wils, G. Kleinberger, J. Janssens, S. Pereson, G. Joris, I. Cuijt, V. Smits, C. Ceuterick-de Groote, C. Van Broeckhoven, and S. Kumar-Singh TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration Proc. Natl. Acad. Sci. U. S. A 107 2010 3858 3863 10.1073/pnas.0912417107
220. E.A. Winkler, J.D. Sengillo, J.S. Sullivan, J.S. Henkel, S.H. Appel, and B.V. Zlokovic Blood-spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis Acta Neuropathol. 125 2013 111 120 10.1007/s00401-012-1039-8
221. Wu, L.-J., 2014. Voltage-gated proton channel HV1 in microglia. Neuroscientist 10.1177/1073858413519864
222. T. Wyss-Coray, C. Lin, D.A. Sanan, L. Mucke, and E. Masliah Chronic overproduction of transforming growth factor-beta1 by astrocytes promotes Alzheimer's disease-like microvascular degeneration in transgenic mice Am. J. Pathol. 156 2000 139 150
223. T. Wyss-Coray, C. Lin, F. Yan, G.Q. Yu, M. Rohde, L. McConlogue, E. Masliah, and L. Mucke TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice Nat. Med. 7 2001 612 618 10.1038/87945
224. T. Wyss-Coray, E. Masliah, M. Mallory, L. McConlogue, K. Johnson-Wood, C. Lin, and L. Mucke Amyloidogenic role of cytokine TGF-beta1 in transgenic mice and in Alzheimer's disease Nature 389 1997 603 606 10.1038/39321
225. M.Q. Xia, and B.T. Hyman Chemokines/chemokine receptors in the central nervous system and Alzheimer's disease J. Neurovirol. 5 1999 32 41 10.3109/13550289909029743
226. Y.-F. Xu, T.F. Gendron, Y.-J. Zhang, W.-L. Lin, S. D'Alton, H. Sheng, M.C. Casey, J. Tong, J. Knight, X. Yu, R. Rademakers, K. Boylan, M. Hutton, E. McGowan, D.W. Dickson, J. Lewis, and L. Petrucelli Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice J. Neurosci. 30 2010 10851 10859 10.1523/JNEUROSCI.1630-10.2010
227. Y.-F. Xu, Y.-J. Zhang, W.-L. Lin, X. Cao, C. Stetler, D.W. Dickson, J. Lewis, and L. Petrucelli Expression of mutant TDP-43 induces neuronal dysfunction in transgenic mice Mol. Neurodegener. 6 2011 73 10.1186/1750-1326-6-73
228. N. Yamamoto, H. Sawada, Y. Izumi, T. Kume, H. Katsuki, S. Shimohama, and A. Akaike Proteasome inhibition induces glutathione synthesis and protects cells from oxidative stress: relevance to Parkinson disease J. Biol. Chem. 282 2007 4364 4372 10.1074/jbc.M603712200
229. C. Yang, H. Wang, T. Qiao, B. Yang, L. Aliaga, L. Qiu, W. Tan, J. Salameh, D.M. McKenna-Yasek, T. Smith, L. Peng, M.J. Moore, R.H. Brown, H. Cai, and Z. Xu Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis Proc. Natl. Acad. Sci. U. S. A 2014 10.1073/pnas.1322641111
230. M.K. Zabel, and W.M. Kirsch From development to dysfunction: microglia and the complement cascade in CNS homeostasis Ageing Res. Rev. 12 2013 749 756 10.1016/j.arr.2013.02.001
231. B. Zhang, C. Gaiteri, L.-G. Bodea, Z. Wang, J. McElwee, A.A. Podtelezhnikov, C. Zhang, T. Xie, L. Tran, R. Dobrin, E. Fluder, B. Clurman, S. Melquist, M. Narayanan, C. Suver, H. Shah, M. Mahajan, T. Gillis, J. Mysore, M.E. MacDonald, J.R. Lamb, D.A. Bennett, C. Molony, D.J. Stone, V. Gudnason, A.J. Myers, E.E. Schadt, H. Neumann, J. Zhu, and V. Emilsson Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease Cell 153 2013 707 720 10.1016/j.cell.2013.03.030
232. W. Zhang, K. Phillips, A.R. Wielgus, J. Liu, A. Albertini, F.A. Zucca, R. Faust, S.Y. Qian, D.S. Miller, C.F. Chignell, B. Wilson, V. Jackson-Lewis, S. Przedborski, D. Joset, J. Loike, J.-S. Hong, D. Sulzer, and L. Zecca Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: implications for progression of Parkinson's disease Neurotox. Res. 19 2011 63 72 10.1007/s12640-009-9140-z
233. W. Zhang, T. Wang, Z. Pei, D.S. Miller, X. Wu, M.L. Block, B. Wilson, W. Zhang, Y. Zhou, J.-S. Hong, and J. Zhang Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease FASEB J. 19 2005 533 542 10.1096/fj.04-2751com
234. W. Zhao, D.R. Beers, J.S. Henkel, W. Zhang, M. Urushitani, J.-P. Julien, and S.H. Appel Extracellular mutant SOD1 induces microglial-mediated motoneuron injury Glia 58 2010 231 243 10.1002/glia.20919
235. Y. Ziv, N. Ron, O. Butovsky, G. Landa, E. Sudai, N. Greenberg, H. Cohen, J. Kipnis, and M. Schwartz Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood Nat. Neurosci. 9 2006 268 275 10.1038/nn1629