title: [Inflammatory mechanisms in amyotrophic lateral sclerosis].
abstract: Neuroinflammation is a pathological hallmark in human amyotrophic lateral sclerosis (ALS) patients and in the transgenic models of the disease. The importance of glial cell activation and pro-inflammatory cytokines in ALS has been confirmed by numerous studies. For instance, tumor necrosis factor-α (TNF-α), a major pro-inflammatory cytokine, activates microglia and cause neurotoxicity in motor neurons. More recently, the relationship of nuclear factor-κB (NF-κB) and motor neuron degeneration has garnered attention since optineurin (OPTN) mutations were reported in familial ALS. OPTN negatively regulates TNF-α-induced NF-κB activation, but OPTN mutations can lead to dysinhibition of NF-κB-induced neurotoxicity. Notably, OPTN-positive inclusions are observed not only in familial ALS with OPTN mutation but also in sporadic ALS and in familial ALS with SOD1 and fused in sarcoma mutations, suggesting that OPTN- and NF-κB-related pathways are relevant to the general pathomechanisms of ALS. In this review, we discuss inflammatory aspects of ALS comprising the roles of cytokines, glial cells, and T cells.
authors.affiliation: Department of Clinical Neuroscience, The University of Tokushima Graduate School, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D000818:Animals; D018797:Cell Cycle Proteins; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D026901:Membrane Transport Proteins; D016328:NF-kappa B / Q000502:physiology; D035582:Transcription Factor TFIIIA / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D018925:Chemokines; D016207:Cytokines; D026901:Membrane Transport Proteins; D016328:NF-kappa B; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA