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The Role of Immune and Inflammatory Mechanisms in ALS

By P.A McCombe and R.D Henderson


Amyotrophic lateral sclerosis (ALS) is a severe progressive neurodegenerative disease. The cause is unknown, but genetic abnormalities have been identified in subjects with familial ALS and also in subjects with sporadic ALS. Environmental factors such as occupational exposure have been shown to be risk factors for the development of ALS. Patients differ in their clinical features and differ in the clinical course of disease. Immune abnormalities have been found in the central nervous system by pathological studies and also in the blood and CSF of subjects with ALS. Inflammation and immune abnormalities are also found in animals with a model of ALS due to mutations in the SOD1 gene. Previously it has been considered that immune abnormalities might contribute to the pathogenesis of disease. However more recently it has become apparent that an immune response can occur as a response to damage to the nervous system and this can be protective

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  1. (2010). A large genome scan for rare CNVs in amyotrophic lateral sclerosis. Hum Mol Genet
  2. (2009). A large-scale international meta-analysis of paraoxonase gene polymorphisms in sporadic ALS. Neurology
  3. (2008). Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase.
  4. (2003). Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway.
  5. (2009). Activation of signal transducer and activator of transcription-3 in the spinal cord of sporadic amyotrophic lateral sclerosis patients. Neurodegener Dis
  6. (2008). Adaptive immune neuroprotection in G93A-SOD1 amyotrophic lateral sclerosis mice. PLoS ONE
  7. (2010). Adaptive immune regulation of glial homeostasis as an immunization strategy for neurodegenerative diseases.
  8. (2008). ALS and FTLD: two faces of TDP-43 proteinopathy.
  9. (2009). ALS in Italian professional soccer players: the risk is still present and could be soccer-specific. Amyotroph Lateral Scler
  10. (2005). ALS-IgG-induced selective motor neurone apoptosis in rat mixed primary spinal cord cultures.
  11. (2006). ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron
  12. (2006). ALS: cytokine profile in cerebrospinal fluid T-cell clones. Amyotroph Lateral Scler
  13. (1989). Alteration in autonomic function and cardiovascular regulation in amyotrophic lateral sclerosis.
  14. (2010). AMPA receptor-mediated neuronal death in sporadic ALS. Neuropathology
  15. (2007). Amyotrophic lateral sclerosis in South-East England: a population-based study. The South-East England register for amyotrophic lateral sclerosis (SEALS Registry). Neuroepidemiology
  16. (2004). Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol
  17. (1994). Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel alpha 1 subunit. Ann Neurol
  18. (2009). Amyotrophic lateral sclerosis, frontotemporal dementia and beyond: the TDP-43 diseases.
  19. (2010). Amyotrophic lateral sclerosis, physical exercise, trauma and sports: results of a population-based pilot case-control study. Amyotroph Lateral Scler
  20. An estimate of amyotrophic lateral sclerosis heritability using twin data.
  21. (1994). and the extended family. Annu Rev Immunol
  22. (1995). Antibodies to calcium channels from ALS patients passively transferred to mice selectively increase intracellular calcium and induce ultrastructural changes in motoneurons. Synapse
  23. (2010). Appearance of phagocytic microglia adjacent to motoneurons in spinal cord tissue from a presymptomatic transgenic rat model of amyotrophic lateral sclerosis.
  24. (1999). Autoimmune maintenance and neuroprotection of the central nervous system.
  25. (2005). Background and gender effects on survival in the TgN(SOD1-G93A)1Gur mouse model of ALS.
  26. (2010). Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models.
  27. (2001). Beneficial immune activity after CNS injury: prospects for vaccination.
  28. (2009). Biomarkers in amyotrophic lateral sclerosis. Lancet Neurol
  29. (2000). Caspase-1 and -3 are sequentially activated in motor neuron death in Cu,Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis.
  30. (2008). CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS.
  31. (2010). Changing face of microglia. Science
  32. (2009). Circulating endotoxin and systemic immune activation in sporadic amyotrophic lateral sclerosis (sALS).
  33. (2010). Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature
  34. (2000). Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: A population-based study. Arch Neurol
  35. (2009). Clinical phenotypes and natural progression for motor neuron disease: analysis from an Australian database. Amyotroph Lateral Scler
  36. (2011). Complement C3c and related protein biomarkers in amyotrophic lateral The Role of Immune and Inflammatory Mechanisms in
  37. (2010). Control of neuroinflammation as a therapeutic strategy for amyotrophic lateral sclerosis and other neurodegenerative disorders. Exp Neurol
  38. (2009). Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol
  39. (2009). Debris clearance by microglia: an essential link between degeneration and regeneration.
  40. (1993). Defining criteria for autoimmune diseases (Witebsky's postulates revisited). Immunol Today
  41. (1984). Deposits of IgG and C3 in the spinal cord and motor cortex of ALS patients.
  42. (2002). Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system. Adv Exp Med Biol
  43. (2009). Development of ALS-like disease in SOD-1 mice deficient of B lymphocytes.
  44. Does inflammation stimulate remyelination?
  45. (2009). Early treatment with noninvasive positive pressure ventilation prolongs survival in Amyotrophic Lateral Sclerosis patients with nocturnal respiratory insufficiency.
  46. (2011). Effect of genetic background on phenotype variability in transgenic mouse models of amyotrophic lateral sclerosis: A window of opportunity in the search for genetic modifiers. Amyotroph Lateral Scler
  47. (2010). Effects of gender in amyotrophic lateral sclerosis. Gend Med
  48. (2007). Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol
  49. (2005). Elevated IL-6 and TNF-alpha levels in patients with ALS: inflammation or hypoxia? Neurology
  50. (2009). Epidemiology of ALS in Italy: a 10-year prospective population-based study. Neurology
  51. (2009). Evaluation of humoral immune response in adaptive immunity in ALS patients during disease progression.
  52. (2005). Evidence for systemic immune system alterations in sporadic amyotrophic lateral sclerosis (sALS).
  53. (2004). Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis
  54. (2004). Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis.
  55. Exposure to chemicals and metals and risk of amyotrophic lateral sclerosis: a systematic review.
  56. (2009). Familial aggregation of amyotrophic lateral sclerosis. Ann Neurol
  57. (2010). From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis. Nat Genet
  58. (2010). FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis.
  59. (2010). FUS mutations in sporadic amyotrophic lateral sclerosis. Neurobiol Aging
  60. (2011). Gene expression profiling in peripheral blood mononuclear cells from patients with sporadic amyotrophic lateral sclerosis (sALS).
  61. (2009). Genome-wide association reveals three SNPs associated with sporadic amyotrophic lateral sclerosis through a twolocus analysis.
  62. (2008). Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis. Neurology
  63. (2010). IFNgamma triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1. Cell Death Differ
  64. (1990). IgG reactivity in the spinal cord and motor cortex in amyotrophic lateral sclerosis. Arch Neurol
  65. (2010). IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients.
  66. (2008). Immune and inflammatory responses to stroke: good or bad?
  67. (2001). Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology
  68. (2009). Immune system alterations in sporadic amyotrophic lateral sclerosis patients suggest an ongoing neuroinflammatory process.
  69. (1991). Immunoglobulins from animal models of motor neuron disease and from human amyotrophic lateral sclerosis patients passively transfer physiological abnormalities to the neuromuscular junction.
  70. (1992). Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue.
  71. (2009). Immunoreactivity of the phosphorylated axonal neurofilament H subunit (pNF-H) in blood of ALS model rodents and ALS patients: evaluation of blood pNF-H as a potential ALS biomarker.
  72. (1990). Immunosuppressive treatment of patients with amyotrophic lateral sclerosis. Acta Neurol Scand
  73. (2008). Incidence and prevalence of amyotrophic lateral sclerosis in Uruguay: a population-based study. Neuroepidemiology
  74. (1996). Incidence of amyotrophic lateral sclerosis in three counties in western Washington state. Neurology
  75. (2010). Increased expression and activation of cytosolic phospholipase A(2) in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. Acta Neuropathol Berl
  76. (2007). Increased IL-13-producing T cells in ALS: positive correlations with disease severity and progression rate.
  77. (2009). Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis.
  78. (2008). Increased resistance to CD4+CD25hi regulatory T cell-mediated suppression in patients with type 1 diabetes. Clin Exp Immunol
  79. (2010). Induction of protective immunity by vaccination with wild-type apo superoxide dismutase 1 in mutant SOD1 transgenic mice.
  80. (2011). Inflammation and oxidative damage in Alzheimer's disease: friend or foe? Front Biosci (Schol Ed)
  81. (2004). 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
  82. (2002). Inflammatory processes in amyotrophic lateral sclerosis. Muscle Nerve
  83. (1999). Innate and adaptive immune responses can be beneficial for CNS repair. Trends Neurosci
  84. (1996). Intravenous immunoglobulin therapy in amyotrophic lateral sclerosis.
  85. (2010). Involvement of immune response in the pathogenesis of amyotrophic lateral sclerosis: a therapeutic opportunity? CNS Neurol Disord Drug Targets
  86. (2009). Latent cluster analysis of ALS phenotypes identifies prognostically differing groups. PLoS ONE
  87. (2007). Lifetime occupation, education, smoking, and risk of ALS. Neurology
  88. (2009). Low-grade systemic inflammation in patients with amyotrophic lateral sclerosis. Acta Neurol Scand
  89. (1993). Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis. Arch Neurol
  90. (2008). Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis. Mult Scler
  91. (2006). MCP-1 chemokine receptor CCR2 is decreased on circulating monocytes in sporadic amyotrophic lateral sclerosis (sALS).
  92. (1996). Microglia: a sensor for pathological events in the CNS. Trends Neurosci
  93. (2002). Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol Dis
  94. (2010). Mitochondrial dysfunction in amyotrophic lateral sclerosis. Biochim Biophys Acta
  95. (2010). Modeling neuroinflammatory pathogenesis of Parkinson's disease. Prog Brain Res
  96. (2011). Modeling the Cumulative Genetic Risk for Multiple Sclerosis from Genome Wide Association Data. Genome Med
  97. (2010). Motor neuron-immune interactions: the vicious circle of ALS.
  98. (2006). Motor unit number estimates--from A to Z.
  99. (2007). Motor unit number estimation using reversible jump Markov chain Monte Carlo.
  100. (2006). Motor Unit Number Estimation—A Bayesian Approach. Biometrics
  101. (2010). Mutant superoxide dismutase 1-induced IL-1beta accelerates ALS pathogenesis.
  102. (2009). Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond.
  103. (2004). Passive transfer of purified IgG from patients with amyotrophic lateral sclerosis to mice results in degeneration of motor neurons accompanied by Ca2+ enhancement.
  104. (2007). Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol
  105. (1983). Peripheral benzodiazepine binding sites: effect of PK 11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide. I. In vitro studies. Life Sci
  106. (2009). Persistent cleavage and nuclear translocation of apoptosis-inducing factor in motor neurons in the spinal cord of sporadic amyotrophic lateral sclerosis patients. Acta Neuropathol Berl
  107. (2007). Positron emission tomography imaging of neuroinflammation. Neurotherapeutics
  108. (2003). Prognosis in amyotrophic lateral sclerosis: a population-based study. Neurology
  109. (2009). Protective autoimmunity in the nervous system. Pharmacol Ther
  110. (2001). Protective autoimmunity: regulation and prospects for vaccination after brain and spinal cord injuries. Trends Mol Med
  111. (2010). Radioisotopic imaging of neuroinflammation.
  112. (1991). Reactions of the immune system in chronic degenerative neurological diseases.
  113. (1989). Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.
  114. (2010). Relationship between neuropathology and disease progression in the SOD1(G93A) ALS mouse. Exp Neurol
  115. (2011). Repeated courses of granulocyte colony-stimulating factor in amyotrophic lateral sclerosis: Clinical and biological results from a prospective multicenter study. Muscle Nerve
  116. (1991). Sensory nerve pathology in amyotrophic lateral sclerosis.
  117. (2009). Sexual dimorphism in autoimmune disease. Curr Mol Med
  118. (2009). Smoking may be considered an established risk factor for sporadic ALS. Neurology
  119. (2010). Sterile inflammatory responses mediated by the NLRP3 inflammasome.
  120. (2010). T cell-microglial dialogue in Parkinson's disease and amyotrophic lateral sclerosis: are we listening? Trends Immunol
  121. (2008). T cells in amyotrophic lateral sclerosis.
  122. (2008). T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS.
  123. (2008). TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet
  124. (2008). The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis.
  125. (2011). The epidemiology and treatment of ALS: Focus on the heterogeneity of the disease and critical appraisal of therapeutic trials. Amyotroph Lateral Scler
  126. (2009). The importance of the SMN genes in the genetics of sporadic ALS. Amyotroph Lateral Scler
  127. (2011). The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond. Cell Mol Immunol
  128. (2009). The molecular links between TDP-43 dysfunction and neurodegeneration. Adv Genet
  129. (2000). The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis.
  130. (2006). The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis. Neurol Sci
  131. (2011). The remedy may lie in ourselves: prospects for immune The Role of Immune and Inflammatory Mechanisms in
  132. (1994). Treatment of ALS with high dose pulse cyclophosphamide.
  133. (2010). Treatment with minocycline after disease onset alters astrocyte reactivity and increases microgliosis in SOD1 mutant mice. Exp Neurol
  134. (2009). Use of respiratory function tests to predict survival in amyotrophic lateral sclerosis. Amyotroph Lateral Scler
  135. (2007). Wholegenome analysis of sporadic amyotrophic lateral sclerosis.
  136. (2009). Workplace exposures and the risk of amyotrophic lateral sclerosis. Environ Health Perspect