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

• Published in: Brain research Vol. 1617; pp. 155 - 173
• Main Authors: Doty, Kevin R, Guillot-Sestier, Marie-Victoire, Town, Terrence
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 18.08.2015
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer׳s disease; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - metabolism; Animals; Astrocytes - immunology; Astrocytes - metabolism; Brain - immunology; Brain - metabolism; Central nervous system; Encephalitis - genetics; Encephalitis - immunology; Humans; Inflammation Mediators - metabolism; Microglia - immunology; Microglia - metabolism; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - immunology; Neurodegenerative Diseases - metabolism; Neuroimmunology; Neuroinflammation; Neurology; Neurons - immunology; Neurons - metabolism; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson׳s disease; Risk Factors; BBB; NRF; pathogen associated molecular patterns; PS; toll-like receptors; C-AMP response element-binding protein; activator protein-1; N-methyl- d-aspartate; MHC; major histocompatibility complex; AP-1; nuclear factor erythroid 2 related factor; transforming growth factor-beta; tumor necrosis factor-alpha; PAMPs; blood–spinal cord barrier; LRRK; nuclear factor erythroid 2-related factor; CX3C chemokine receptor; nitric oxide; AD; IL; triggering receptor expressed on myeloid cells; intracellular adhesion molecule-1; Alzheimer׳s disease; c/EBP; central nervous system; blood brain barrier; IRAK; activating transcription factor; TYROBP; superoxide dismutase; apolipoprotein E; toll-interleukin receptor domain-containing adapter protein; human leukocyte antigen-DR; IRF; TRIF; CNS; lymphocyte function-associated antigen-1; cytotoxic T lymphocytes; late-onset AD; β-APP; DAMPs; CREB; NMDA; NLRP3; TGF-β; ApoE; chemokine (C-X-C motif) ligand; interleukin-1 receptor-associated kinase; danger associated molecular patterns; NOD-like receptor family, pyrin domain containing 3; SOD; Neuroinflammation; COX; BSCB; CCAAT/enhancer binding protein; CR; ATF; adenosine triphosphate; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; β-amyloid precursor protein; nuclear factor-kappaB; MPTP; TIR; ATP; oxidative stress; CXCL; TREM; ALS; ICAM-1; amyotrophic lateral sclerosis; MyD88; UTP; NF-κB; Cyclooxygenase; natural killer; CX3CR; presenilin; iNOS; NFR; MAPKs; LFA-1; leucine-rich repeat kinase; SNpc; chemokine ligand; TIRAP; BCSFB; HLA-DR; cerebrospinal fluid; ROS; blood–cerebrospinal fluid barrier; interferon regulatory factor; NK; NO; LOAD; glutathione; PRRs; CTLs; myeloid differentiation primary response 88; inducible nitric oxide synthase; complement receptor; CSF; reactive oxygen species; TYRO protein tyrosine kinase-binding protein; interleukin; Neuroimmunology; GSH; suppressor of cytokine signaling; OS; SOCS; CCL; TIR-domain-containing adapter-inducing interferon-β; pattern recognition receptors; substantia nigra pars compacta; CCR; PD; TNF-α; mitogen-activated protein kinases; C-C chemokine receptor; uridine triphosphate; Parkinson׳s disease; TLRs; toll-interleukin receptor; Central nervous system; Amyotrophic lateral sclerosis
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2014.09.008

Abstract Neurodegenerative diseases share common features, including catastrophic neuronal loss that leads to cognitive or motor dysfunction. Neuronal injury occurs in an inflammatory milieu that is populated by resident and sometimes, infiltrating, immune cells − all of which participate in a complex interplay between secreted inflammatory modulators and activated immune cell surface receptors. The importance of these immunomodulators is highlighted by the number of immune factors that have been associated with increased risk of neurodegeneration in recent genome-wide association studies. One of the more difficult tasks for designing therapeutic strategies for immune modulation against neurodegenerative diseases is teasing apart beneficial from harmful signals. In this regard, learning more about the immune components of these diseases has yielded common themes. These unifying concepts should eventually enable immune-based therapeutics for treatment of Alzheimer׳s and Parkinson׳s diseases and amyotrophic lateral sclerosis. Targeted immune modulation should be possible to temper maladaptive factors, enabling beneficial immune responses in the context of neurodegenerative diseases. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.