Skip to main content
Erschienen in: Journal of Neurology 9/2016

12.02.2016 | Review

Immune-mediated processes in neurodegeneration: where do we stand?

verfasst von: Marc Fakhoury

Erschienen in: Journal of Neurology | Ausgabe 9/2016

Einloggen, um Zugang zu erhalten

Abstract

Neurodegeneration is a pathological condition that predominantly affects neurons. It represents a large spectrum of disorders with heterogeneous symptoms and distinct clinical features. In addition to the devastating effects it can have on the affected individual, it constitutes a heavy burden to the society in terms of health care costs. Although the exact cause of neurodegeneration is not known, there are plenty of evidences supporting the notion that the immune system is strongly associated with various forms of neurodegenerative diseases. Given the numerous functions of immune cells, a change in their expression can either be beneficial or deleterious to the host. A better understanding of the molecular and cellular processes in neurodegeneration is therefore needed. This could facilitate the development of new therapeutic targets and provide effective means to dampen the progression of neurodegenerative disorders. The overarching aim of this paper is to provide an overview of the roles that the innate and adaptive immune systems play in the central nervous system, and to discuss their beneficial or detrimental effects during neurodegeneration. This paper also critically examines the contribution of immune and inflammatory-mediated responses in the development of neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and amyloid lateral sclerosis by illustrating key findings from animal and human studies.
Literatur
2.
Zurück zum Zitat Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM (2009) Finding the missing heritability of complex diseases. Nature 461:747–753. doi:10.1038/nature08494 PubMedPubMedCentralCrossRef Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM (2009) Finding the missing heritability of complex diseases. Nature 461:747–753. doi:10.​1038/​nature08494 PubMedPubMedCentralCrossRef
3.
Zurück zum Zitat Wyss-Coray T, Mucke L (2002) Inflammation in neurodegenerative disease—a double-edged sword. Neuron 35:419–432PubMedCrossRef Wyss-Coray T, Mucke L (2002) Inflammation in neurodegenerative disease—a double-edged sword. Neuron 35:419–432PubMedCrossRef
12.
Zurück zum Zitat Facci L, Barbierato M, Marinelli C, Argentini C, Skaper SD, Giusti P (2014) Toll-like receptors 2, -3 and -4 prime microglia but not astrocytes across central nervous system regions for ATP-dependent interleukin-1beta release. Sci Rep 4:6824. doi:10.1038/srep06824 PubMedCrossRef Facci L, Barbierato M, Marinelli C, Argentini C, Skaper SD, Giusti P (2014) Toll-like receptors 2, -3 and -4 prime microglia but not astrocytes across central nervous system regions for ATP-dependent interleukin-1beta release. Sci Rep 4:6824. doi:10.​1038/​srep06824 PubMedCrossRef
16.
Zurück zum Zitat Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S, Paquette N, Deane RJ, Thiyagarajan M, Zarcone T, Fritz G, Friedman AE, Miller BL, Zlokovic BV (2012) A multimodal RAGE-specific inhibitor reduces amyloid beta-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest 122:1377–1392. doi:10.1172/JCI58642 PubMedPubMedCentralCrossRef Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S, Paquette N, Deane RJ, Thiyagarajan M, Zarcone T, Fritz G, Friedman AE, Miller BL, Zlokovic BV (2012) A multimodal RAGE-specific inhibitor reduces amyloid beta-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest 122:1377–1392. doi:10.​1172/​JCI58642 PubMedPubMedCentralCrossRef
17.
Zurück zum Zitat Beynon V, Cotofana S, Brand S, Lohse P, Mair A, Wagner S, Mussack T, Ochsenkuhn T, Folwaczny M, Folwaczny C, Glas J, Torok HP (2008) NOD2/CARD15 genotype influences MDP-induced cytokine release and basal IL-12p40 levels in primary isolated peripheral blood monocytes. Inflamm Bowel Dis 14:1033–1040. doi:10.1002/ibd.20441 PubMedCrossRef Beynon V, Cotofana S, Brand S, Lohse P, Mair A, Wagner S, Mussack T, Ochsenkuhn T, Folwaczny M, Folwaczny C, Glas J, Torok HP (2008) NOD2/CARD15 genotype influences MDP-induced cytokine release and basal IL-12p40 levels in primary isolated peripheral blood monocytes. Inflamm Bowel Dis 14:1033–1040. doi:10.​1002/​ibd.​20441 PubMedCrossRef
21.
Zurück zum Zitat Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E, Halle A, Korte M, Latz E, Golenbock DT (2013) NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature 493:674–678. doi:10.1038/nature11729 PubMedCrossRef Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E, Halle A, Korte M, Latz E, Golenbock DT (2013) NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature 493:674–678. doi:10.​1038/​nature11729 PubMedCrossRef
41.
Zurück zum Zitat Fiala M, Chattopadhay M, La Cava A, Tse E, Liu G, Lourenco E, Eskin A, Liu PT, Magpantay L, Tse S, Mahanian M, Weitzman R, Tong J, Nguyen C, Cho T, Koo P, Sayre J, Martinez-Maza O, Rosenthal MJ, Wiedau-Pazos M (2010) IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients. J Neuroinflammation 7:76. doi:10.1186/1742-2094-7-76 PubMedPubMedCentralCrossRef Fiala M, Chattopadhay M, La Cava A, Tse E, Liu G, Lourenco E, Eskin A, Liu PT, Magpantay L, Tse S, Mahanian M, Weitzman R, Tong J, Nguyen C, Cho T, Koo P, Sayre J, Martinez-Maza O, Rosenthal MJ, Wiedau-Pazos M (2010) IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients. J Neuroinflammation 7:76. doi:10.​1186/​1742-2094-7-76 PubMedPubMedCentralCrossRef
45.
Zurück zum Zitat Lunnon K, Ibrahim Z, Proitsi P, Lourdusamy A, Newhouse S, Sattlecker M, Furney S, Saleem M, Soininen H, Kloszewska I, Mecocci P, Tsolaki M, Vellas B, Coppola G, Geschwind D, Simmons A, Lovestone S, Dobson R, Hodges A, AddNeuroMed C (2012) Mitochondrial dysfunction and immune activation are detectable in early Alzheimer’s disease blood. J Alzheimers Dis 30:685–710. doi:10.3233/JAD-2012-111592 PubMed Lunnon K, Ibrahim Z, Proitsi P, Lourdusamy A, Newhouse S, Sattlecker M, Furney S, Saleem M, Soininen H, Kloszewska I, Mecocci P, Tsolaki M, Vellas B, Coppola G, Geschwind D, Simmons A, Lovestone S, Dobson R, Hodges A, AddNeuroMed C (2012) Mitochondrial dysfunction and immune activation are detectable in early Alzheimer’s disease blood. J Alzheimers Dis 30:685–710. doi:10.​3233/​JAD-2012-111592 PubMed
46.
55.
58.
59.
Zurück zum Zitat Gao X, Hu X, Qian L, Yang S, Zhang W, Zhang D, Wu X, Fraser A, Wilson B, Flood PM, Block M, Hong JS (2008) Formyl-methionyl-leucyl-phenylalanine-induced dopaminergic neurotoxicity via microglial activation: a mediator between peripheral infection and neurodegeneration? Environ Health Perspect 116:593–598. doi:10.1289/ehp.11031 PubMedPubMedCentralCrossRef Gao X, Hu X, Qian L, Yang S, Zhang W, Zhang D, Wu X, Fraser A, Wilson B, Flood PM, Block M, Hong JS (2008) Formyl-methionyl-leucyl-phenylalanine-induced dopaminergic neurotoxicity via microglial activation: a mediator between peripheral infection and neurodegeneration? Environ Health Perspect 116:593–598. doi:10.​1289/​ehp.​11031 PubMedPubMedCentralCrossRef
60.
Zurück zum Zitat Bodea LG, Wang Y, Linnartz-Gerlach B, Kopatz J, Sinkkonen L, Musgrove R, Kaoma T, Muller A, Vallar L, Di Monte DA, Balling R, Neumann H (2014) Neurodegeneration by activation of the microglial complement-phagosome pathway. J Neurosci 34:8546–8556. doi:10.1523/JNEUROSCI.5002-13.2014 PubMedCrossRef Bodea LG, Wang Y, Linnartz-Gerlach B, Kopatz J, Sinkkonen L, Musgrove R, Kaoma T, Muller A, Vallar L, Di Monte DA, Balling R, Neumann H (2014) Neurodegeneration by activation of the microglial complement-phagosome pathway. J Neurosci 34:8546–8556. doi:10.​1523/​JNEUROSCI.​5002-13.​2014 PubMedCrossRef
61.
Zurück zum Zitat Suzumura A (2013) Neuron-microglia interaction in neuroinflammation. Curr Protein Pept Sci 14:16–20PubMedCrossRef Suzumura A (2013) Neuron-microglia interaction in neuroinflammation. Curr Protein Pept Sci 14:16–20PubMedCrossRef
62.
Zurück zum Zitat Carnevale D, De Simone R, Minghetti L (2007) Microglia-neuron interaction in inflammatory and degenerative diseases: role of cholinergic and noradrenergic systems. CNS Neurol Disord Drug Targets 6:388–397PubMedCrossRef Carnevale D, De Simone R, Minghetti L (2007) Microglia-neuron interaction in inflammatory and degenerative diseases: role of cholinergic and noradrenergic systems. CNS Neurol Disord Drug Targets 6:388–397PubMedCrossRef
63.
66.
Zurück zum Zitat Hucke S, Flossdorf J, Grutzke B, Dunay IR, Frenzel K, Jungverdorben J, Linnartz B, Mack M, Peitz M, Brustle O, Kurts C, Klockgether T, Neumann H, Prinz M, Wiendl H, Knolle P, Klotz L (2012) Licensing of myeloid cells promotes central nervous system autoimmunity and is controlled by peroxisome proliferator-activated receptor gamma. Brain 135:1586–1605. doi:10.1093/brain/aws058 PubMedCrossRef Hucke S, Flossdorf J, Grutzke B, Dunay IR, Frenzel K, Jungverdorben J, Linnartz B, Mack M, Peitz M, Brustle O, Kurts C, Klockgether T, Neumann H, Prinz M, Wiendl H, Knolle P, Klotz L (2012) Licensing of myeloid cells promotes central nervous system autoimmunity and is controlled by peroxisome proliferator-activated receptor gamma. Brain 135:1586–1605. doi:10.​1093/​brain/​aws058 PubMedCrossRef
72.
79.
Zurück zum Zitat Yao Y, Vent-Schmidt J, McGeough MD, Wong M, Hoffman HM, Steiner TS, Levings MK (2015) Tr1 cells, but not Foxp3+ regulatory T cells, suppress NLRP3 inflammasome activation via an IL-10-dependent mechanism. J Immunol 195:488–497. doi:10.4049/jimmunol.1403225 PubMedCrossRef Yao Y, Vent-Schmidt J, McGeough MD, Wong M, Hoffman HM, Steiner TS, Levings MK (2015) Tr1 cells, but not Foxp3+ regulatory T cells, suppress NLRP3 inflammasome activation via an IL-10-dependent mechanism. J Immunol 195:488–497. doi:10.​4049/​jimmunol.​1403225 PubMedCrossRef
80.
Zurück zum Zitat Martinez-Forero I, Garcia-Munoz R, Martinez-Pasamar S, Inoges S, Lopez-Diaz de Cerio A, Palacios R, Sepulcre J, Moreno B, Gonzalez Z, Fernandez-Diez B, Melero I, Bendandi M, Villoslada P (2008) IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis. Eur J Immunol 38:576–586. doi:10.1002/eji.200737271 PubMedCrossRef Martinez-Forero I, Garcia-Munoz R, Martinez-Pasamar S, Inoges S, Lopez-Diaz de Cerio A, Palacios R, Sepulcre J, Moreno B, Gonzalez Z, Fernandez-Diez B, Melero I, Bendandi M, Villoslada P (2008) IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis. Eur J Immunol 38:576–586. doi:10.​1002/​eji.​200737271 PubMedCrossRef
82.
Zurück zum Zitat Brun V, Neveu V, Pers YM, Fabre S, Quatannens B, Bastian H, Clerget-Chossat N, Jorgensen C, Foussat A (2011) Isolation of functional autologous collagen-II specific IL-10 producing Tr1 cell clones from rheumatoid arthritis blood. Int Immunopharmacol 11:1074–1078. doi:10.1016/j.intimp.2011.03.001 PubMedCrossRef Brun V, Neveu V, Pers YM, Fabre S, Quatannens B, Bastian H, Clerget-Chossat N, Jorgensen C, Foussat A (2011) Isolation of functional autologous collagen-II specific IL-10 producing Tr1 cell clones from rheumatoid arthritis blood. Int Immunopharmacol 11:1074–1078. doi:10.​1016/​j.​intimp.​2011.​03.​001 PubMedCrossRef
84.
Zurück zum Zitat 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. doi:10.1189/jlb.0507296 PubMedCrossRef 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. doi:10.​1189/​jlb.​0507296 PubMedCrossRef
85.
Zurück zum Zitat Beers DR, Henkel JS, Zhao W, Wang J, Huang A, Wen S, Liao B, Appel SH (2011) Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 134:1293–1314. doi:10.1093/brain/awr074 PubMedPubMedCentralCrossRef Beers DR, Henkel JS, Zhao W, Wang J, Huang A, Wen S, Liao B, Appel SH (2011) Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 134:1293–1314. doi:10.​1093/​brain/​awr074 PubMedPubMedCentralCrossRef
87.
Zurück zum Zitat Lin X, Chen M, Liu Y, Guo Z, He X, Brand D, Zheng SG (2013) Advances in distinguishing natural from induced Foxp3(+) regulatory T cells. Int J Clin Exp Pathol 6:116–123PubMedPubMedCentral Lin X, Chen M, Liu Y, Guo Z, He X, Brand D, Zheng SG (2013) Advances in distinguishing natural from induced Foxp3(+) regulatory T cells. Int J Clin Exp Pathol 6:116–123PubMedPubMedCentral
94.
Zurück zum Zitat Liu H, Rohowsky-Kochan C (2008) Regulation of IL-17 in human CCR6+ effector memory T cells. J Immunol 180:7948–7957PubMedCrossRef Liu H, Rohowsky-Kochan C (2008) Regulation of IL-17 in human CCR6+ effector memory T cells. J Immunol 180:7948–7957PubMedCrossRef
96.
Zurück zum Zitat Junker A, Ivanidze J, Malotka J, Eiglmeier I, Lassmann H, Wekerle H, Meinl E, Hohlfeld R, Dornmair K (2007) Multiple sclerosis: T-cell receptor expression in distinct brain regions. Brain 130:2789–2799. doi:10.1093/brain/awm214 PubMedCrossRef Junker A, Ivanidze J, Malotka J, Eiglmeier I, Lassmann H, Wekerle H, Meinl E, Hohlfeld R, Dornmair K (2007) Multiple sclerosis: T-cell receptor expression in distinct brain regions. Brain 130:2789–2799. doi:10.​1093/​brain/​awm214 PubMedCrossRef
97.
99.
Zurück zum Zitat Lee YH, Ishida Y, Rifa’i M, Shi Z, Isobe K, Suzuki H (2008) Essential role of CD8+ CD122+ regulatory T cells in the recovery from experimental autoimmune encephalomyelitis. J Immunol 180:825–832PubMedCrossRef Lee YH, Ishida Y, Rifa’i M, Shi Z, Isobe K, Suzuki H (2008) Essential role of CD8+ CD122+ regulatory T cells in the recovery from experimental autoimmune encephalomyelitis. J Immunol 180:825–832PubMedCrossRef
106.
Zurück zum Zitat Petty MA, Lo EH (2002) Junctional complexes of the blood-brain barrier: permeability changes in neuroinflammation. Prog Neurobiol 68:311–323PubMedCrossRef Petty MA, Lo EH (2002) Junctional complexes of the blood-brain barrier: permeability changes in neuroinflammation. Prog Neurobiol 68:311–323PubMedCrossRef
108.
Zurück zum Zitat Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K, Johansson BR, Betsholtz C (2010) Pericytes regulate the blood-brain barrier. Nature 468:557–561. doi:10.1038/nature09522 PubMedCrossRef Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K, Johansson BR, Betsholtz C (2010) Pericytes regulate the blood-brain barrier. Nature 468:557–561. doi:10.​1038/​nature09522 PubMedCrossRef
116.
Zurück zum Zitat El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13:432–438. doi:10.1038/nm1555 PubMedCrossRef El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (2007) Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 13:432–438. doi:10.​1038/​nm1555 PubMedCrossRef
118.
Zurück zum Zitat Marchese M, Cowan D, Head E, Ma D, Karimi K, Ashthorpe V, Kapadia M, Zhao H, Davis P, Sakic B (2014) Autoimmune manifestations in the 3xTg-AD model of Alzheimer’s disease. J Alzheimers Dis 39:191–210. doi:10.3233/JAD-131490 PubMedPubMedCentral Marchese M, Cowan D, Head E, Ma D, Karimi K, Ashthorpe V, Kapadia M, Zhao H, Davis P, Sakic B (2014) Autoimmune manifestations in the 3xTg-AD model of Alzheimer’s disease. J Alzheimers Dis 39:191–210. doi:10.​3233/​JAD-131490 PubMedPubMedCentral
119.
Zurück zum Zitat Craig-Schapiro R, Perrin RJ, Roe CM, Xiong C, Carter D, Cairns NJ, Mintun MA, Peskind ER, Li G, Galasko DR, Clark CM, Quinn JF, D’Angelo G, Malone JP, Townsend RR, Morris JC, Fagan AM, Holtzman DM (2010) YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol Psychiatry 68:903–912. doi:10.1016/j.biopsych.2010.08.025 PubMedPubMedCentralCrossRef Craig-Schapiro R, Perrin RJ, Roe CM, Xiong C, Carter D, Cairns NJ, Mintun MA, Peskind ER, Li G, Galasko DR, Clark CM, Quinn JF, D’Angelo G, Malone JP, Townsend RR, Morris JC, Fagan AM, Holtzman DM (2010) YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol Psychiatry 68:903–912. doi:10.​1016/​j.​biopsych.​2010.​08.​025 PubMedPubMedCentralCrossRef
120.
Zurück zum Zitat Yokokura MMN, Yagi S, Yoshikawa E, Kikuchi M, Yoshihara Y, Wakuda T, Sugihara G, Takebayashi K, Suda S, Iwata Y, Ueki T, Tsuchiya KJ, Suzuki K, Nakamura K, Ouchi Y (2011) In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 38:343–351PubMedCrossRef Yokokura MMN, Yagi S, Yoshikawa E, Kikuchi M, Yoshihara Y, Wakuda T, Sugihara G, Takebayashi K, Suda S, Iwata Y, Ueki T, Tsuchiya KJ, Suzuki K, Nakamura K, Ouchi Y (2011) In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 38:343–351PubMedCrossRef
121.
Zurück zum Zitat Koronyo Y, Salumbides BC, Sheyn J, Pelissier L, Li S, Ljubimov V, Moyseyev M, Daley D, Fuchs DT, Pham M, Black KL, Rentsendorj A, Koronyo-Hamaoui M (2015) Therapeutic effects of glatiramer acetate and grafted CD115+ monocytes in a mouse model of Alzheimer’s disease. Brain 138:2399–2422. doi:10.1093/brain/awv150 PubMedPubMedCentralCrossRef Koronyo Y, Salumbides BC, Sheyn J, Pelissier L, Li S, Ljubimov V, Moyseyev M, Daley D, Fuchs DT, Pham M, Black KL, Rentsendorj A, Koronyo-Hamaoui M (2015) Therapeutic effects of glatiramer acetate and grafted CD115+ monocytes in a mouse model of Alzheimer’s disease. Brain 138:2399–2422. doi:10.​1093/​brain/​awv150 PubMedPubMedCentralCrossRef
122.
Zurück zum Zitat Baruch K, Rosenzweig N, Kertser A, Deczkowska A, Sharif AM, Spinrad A, Tsitsou-Kampeli A, Sarel A, Cahalon L, Schwartz M (2015) Breaking immune tolerance by targeting Foxp3(+) regulatory T cells mitigates Alzheimer’s disease pathology. Nat Commun 6:7967. doi:10.1038/ncomms8967 PubMedPubMedCentralCrossRef Baruch K, Rosenzweig N, Kertser A, Deczkowska A, Sharif AM, Spinrad A, Tsitsou-Kampeli A, Sarel A, Cahalon L, Schwartz M (2015) Breaking immune tolerance by targeting Foxp3(+) regulatory T cells mitigates Alzheimer’s disease pathology. Nat Commun 6:7967. doi:10.​1038/​ncomms8967 PubMedPubMedCentralCrossRef
131.
Zurück zum Zitat Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S (2009) Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 119:182–192. doi:10.1172/JCI36470 PubMed Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S (2009) Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 119:182–192. doi:10.​1172/​JCI36470 PubMed
133.
134.
Zurück zum Zitat Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, Eggert K, Oertel W, Banati RB, Brooks DJ (2006) In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis 21:404–412. doi:10.1016/j.nbd.2005.08.002 PubMedCrossRef Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, Eggert K, Oertel W, Banati RB, Brooks DJ (2006) In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis 21:404–412. doi:10.​1016/​j.​nbd.​2005.​08.​002 PubMedCrossRef
141.
Zurück zum Zitat Airas L, Dickens AM, Elo P, Marjamaki P, Johansson J, Eskola O, Jones PA, Trigg W, Solin O, Haaparanta-Solin M, Anthony DC, Rinne J (2015) In vivo PET imaging demonstrates diminished microglial activation after fingolimod treatment in an animal model of multiple sclerosis. J Nucl Med 56:305–310. doi:10.2967/jnumed.114.149955 PubMedCrossRef Airas L, Dickens AM, Elo P, Marjamaki P, Johansson J, Eskola O, Jones PA, Trigg W, Solin O, Haaparanta-Solin M, Anthony DC, Rinne J (2015) In vivo PET imaging demonstrates diminished microglial activation after fingolimod treatment in an animal model of multiple sclerosis. J Nucl Med 56:305–310. doi:10.​2967/​jnumed.​114.​149955 PubMedCrossRef
143.
144.
145.
Zurück zum Zitat Kallaur AP, Oliveira SR, Colado Simao AN, Delicato de Almeida ER, Kaminami Morimoto H, Lopes J, de Carvalho Jennings Pereira WL, Marques Andrade R, Muliterno Pelegrino L, Donizete Borelli S, Kaimen-Maciel DR, Reiche EM (2013) Cytokine profile in relapsingremitting multiple sclerosis patients and the association between progression and activity of the disease. Mol Med Rep 7:1010–1020. doi:10.3892/mmr.2013.1256 PubMed Kallaur AP, Oliveira SR, Colado Simao AN, Delicato de Almeida ER, Kaminami Morimoto H, Lopes J, de Carvalho Jennings Pereira WL, Marques Andrade R, Muliterno Pelegrino L, Donizete Borelli S, Kaimen-Maciel DR, Reiche EM (2013) Cytokine profile in relapsingremitting multiple sclerosis patients and the association between progression and activity of the disease. Mol Med Rep 7:1010–1020. doi:10.​3892/​mmr.​2013.​1256 PubMed
148.
Zurück zum Zitat Rinaldi L, Gallo P, Calabrese M, Ranzato F, Luise D, Colavito D, Motta M, Guglielmo A, Del Giudice E, Romualdi C, Ragazzi E, D’Arrigo A, Dalle Carbonare M, Leontino B, Leon A (2006) Longitudinal analysis of immune cell phenotypes in early stage multiple sclerosis: distinctive patterns characterize MRI-active patients. Brain 129:1993–2007. doi:10.1093/brain/awl179 PubMedCrossRef Rinaldi L, Gallo P, Calabrese M, Ranzato F, Luise D, Colavito D, Motta M, Guglielmo A, Del Giudice E, Romualdi C, Ragazzi E, D’Arrigo A, Dalle Carbonare M, Leontino B, Leon A (2006) Longitudinal analysis of immune cell phenotypes in early stage multiple sclerosis: distinctive patterns characterize MRI-active patients. Brain 129:1993–2007. doi:10.​1093/​brain/​awl179 PubMedCrossRef
149.
Zurück zum Zitat von Budingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L, Glanville J, Cree BA, Gourraud PA, Schwartzburg A, Huerta G, Telman D, Sundar PD, Casey T, Cox DR, Hauser SL (2012) B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest 122:4533–4543. doi:10.1172/JCI63842 CrossRef von Budingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L, Glanville J, Cree BA, Gourraud PA, Schwartzburg A, Huerta G, Telman D, Sundar PD, Casey T, Cox DR, Hauser SL (2012) B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest 122:4533–4543. doi:10.​1172/​JCI63842 CrossRef
151.
Zurück zum Zitat Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH, HERMES Trial Group (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 358:676–688. doi:10.1056/NEJMoa0706383 PubMedCrossRef Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH, HERMES Trial Group (2008) B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 358:676–688. doi:10.​1056/​NEJMoa0706383 PubMedCrossRef
152.
Zurück zum Zitat Hawker K, O’Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, Chin P, Smith CH, OLYMPUS trail group (2009) Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 66:460–471. doi:10.1002/ana.21867 PubMedCrossRef Hawker K, O’Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, Chin P, Smith CH, OLYMPUS trail group (2009) Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol 66:460–471. doi:10.​1002/​ana.​21867 PubMedCrossRef
153.
Zurück zum Zitat Chio A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA, White LA (2013) Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 41:118–130. doi:10.1159/000351153 PubMedPubMedCentralCrossRef Chio A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA, White LA (2013) Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 41:118–130. doi:10.​1159/​000351153 PubMedPubMedCentralCrossRef
155.
157.
Zurück zum Zitat Lewis KE, Rasmussen AL, Bennett W, King A, West AK, Chung RS, Chuah MI (2014) Microglia and motor neurons during disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis: changes in arginase1 and inducible nitric oxide synthase. J Neuroinflammation 11:55. doi:10.1186/1742-2094-11-55 PubMedPubMedCentralCrossRef Lewis KE, Rasmussen AL, Bennett W, King A, West AK, Chung RS, Chuah MI (2014) Microglia and motor neurons during disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis: changes in arginase1 and inducible nitric oxide synthase. J Neuroinflammation 11:55. doi:10.​1186/​1742-2094-11-55 PubMedPubMedCentralCrossRef
159.
Zurück zum Zitat Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, Kollias G, Cleveland DW (2006) Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312:1389–1392. doi:10.1126/science.1123511 PubMedCrossRef Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, Kollias G, Cleveland DW (2006) Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312:1389–1392. doi:10.​1126/​science.​1123511 PubMedCrossRef
160.
Zurück zum Zitat Yamanaka K, Chun SJ, Boillee S, Fujimori-Tonou N, Yamashita H, Gutmann DH, Takahashi R, Misawa H, Cleveland DW (2008) Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci 11:251–253. doi:10.1038/nn2047 PubMedPubMedCentralCrossRef Yamanaka K, Chun SJ, Boillee S, Fujimori-Tonou N, Yamashita H, Gutmann DH, Takahashi R, Misawa H, Cleveland DW (2008) Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci 11:251–253. doi:10.​1038/​nn2047 PubMedPubMedCentralCrossRef
161.
Zurück zum Zitat Woodruff TM, Costantini KJ, Crane JW, Atkin JD, Monk PN, Taylor SM, Noakes PG (2008) The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J Immunol 181:8727–8734PubMedCrossRef Woodruff TM, Costantini KJ, Crane JW, Atkin JD, Monk PN, Taylor SM, Noakes PG (2008) The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J Immunol 181:8727–8734PubMedCrossRef
162.
Zurück zum Zitat Haidet-Phillips AM, Hester ME, Miranda CJ, Meyer K, Braun L, Frakes A, Song S, Likhite S, Murtha MJ, Foust KD, Rao M, Eagle A, Kammesheidt A, Christensen A, Mendell JR, Burghes AH, Kaspar BK (2011) Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol 29:824–828. doi:10.1038/nbt.1957 PubMedPubMedCentralCrossRef Haidet-Phillips AM, Hester ME, Miranda CJ, Meyer K, Braun L, Frakes A, Song S, Likhite S, Murtha MJ, Foust KD, Rao M, Eagle A, Kammesheidt A, Christensen A, Mendell JR, Burghes AH, Kaspar BK (2011) Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol 29:824–828. doi:10.​1038/​nbt.​1957 PubMedPubMedCentralCrossRef
163.
164.
Zurück zum Zitat Mantovani S, Garbelli S, Pasini A, Alimonti D, Perotti C, Melazzini M, Bendotti C, Mora G (2009) Immune system alterations in sporadic amyotrophic lateral sclerosis patients suggest an ongoing neuroinflammatory process. J Neuroimmunol 210:73–79. doi:10.1016/j.jneuroim.2009.02.012 PubMedCrossRef Mantovani S, Garbelli S, Pasini A, Alimonti D, Perotti C, Melazzini M, Bendotti C, Mora G (2009) Immune system alterations in sporadic amyotrophic lateral sclerosis patients suggest an ongoing neuroinflammatory process. J Neuroimmunol 210:73–79. doi:10.​1016/​j.​jneuroim.​2009.​02.​012 PubMedCrossRef
Metadaten
Titel
Immune-mediated processes in neurodegeneration: where do we stand?
verfasst von
Marc Fakhoury
Publikationsdatum
12.02.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 9/2016
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-016-8052-0

Weitere Artikel der Ausgabe 9/2016

Journal of Neurology 9/2016 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Neu im Fachgebiet Neurologie

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.