title: Non-neuronal Cells in ALS: Role of Glial, Immune cells and Blood-CNS Barriers.
abstract: Neurological dysfunction and motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is strongly associated with neuroinflammation reflected by activated microglia and astrocytes in the CNS. In ALS endogenous triggers in the CNS such as aggregated protein and misfolded proteins activate a pathogenic response by innate immune cells. However, there is also strong evidence for a neuroprotective immune response in ALS. Emerging evidence also reveals changes in the peripheral adaptive immune responses as well as alterations in the blood brain barrier that may aid traffic of lymphocytes and antibodies into the CNS. Understanding the triggers of neuroinflammation is key to controlling neuronal loss. Here, we review the current knowledge regarding the roles of non-neuronal cells as well as the innate and adaptive immune responses in ALS. Existing ALS animal models, in particular genetic rodent models, are very useful to study the underlying pathogenic mechanisms of motor neuron degeneration. We also discuss the approaches used to target the pathogenic immune responses and boost the neuroprotective immune pathways as novel immunotherapies for ALS.
authors.affiliation: Neuroimmunology Unit, Queen Mary University of London, Neuroscience Centre, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Puentes
authors.affiliation: Neuroimmunology Unit, Queen Mary University of London, Neuroscience Centre, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Malaspina
authors.affiliation: Delta Crystallon, 2333 CK Leiden, The Netherlands.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: van Noort
authors.affiliation: Neuroimmunology Unit, Queen Mary University of London, Neuroscience Centre, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK.|Department of Pathology, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000503:physiopathology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000503:physiopathology*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*
keywords: ALS; glia; immune regulation; neurodegeneration; protection; therapy