{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:33:56Z","timestamp":1780410836744,"version":"3.54.1"},"reference-count":176,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,10,25]],"date-time":"2014-10-25T00:00:00Z","timestamp":1414195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The immune system is inextricably linked with many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a devastating neuromuscular disorder affecting motor cell function with an average survival of 3 years from symptoms onset. In ALS, there is a dynamic interplay between the resident innate immune cells, that is, microglia and astrocytes, which may become progressively harmful to motor neurons. Although innate and adaptive immune responses are associated with progressive neurodegeneration, in the early stages of ALS immune activation pathways are primarily considered to be beneficial promoting neuronal repair of the damaged tissues, though a harmful effect of T cells at this stage of disease has also been observed. In addition, although auto-antibodies against neuronal antigens are present in ALS, it is unclear whether these arise as a primary or secondary event to neuronal damage, and whether the auto-antibodies are indeed pathogenic. Understanding how the immune system contributes to the fate of motor cells in ALS may shed light on the triggers of disease as well as on the mechanisms contributing to the propagation of the pathology. Immune markers may also act as biomarkers while pathways involved in immune action may be targets of new therapeutic strategies. Here, we review the modalities by which the immune system senses the core pathological process in motor neuron disorders, focusing on tissue-specific immune responses in the neuromuscular junction and in the neuroaxis observed in affected individuals and in animal models of ALS. We elaborate on existing data on the immunological fingerprint of ALS that could be used to identify clues on the disease origin and patterns of progression.<\/jats:p>","DOI":"10.1093\/intimm\/dxu099","type":"journal-article","created":{"date-parts":[[2014,10,26]],"date-time":"2014-10-26T01:15:43Z","timestamp":1414286143000},"page":"117-129","source":"Crossref","is-referenced-by-count":89,"title":["Disease origin and progression in amyotrophic lateral sclerosis: an immunology perspective"],"prefix":"10.1093","volume":"27","author":[{"given":"Andrea","family":"Malaspina","sequence":"first","affiliation":[{"name":"Neuroscience and Trauma Centre, Blizard Building, Institute of Cell and Molecular Medicine, Neuroimmunology Department, Barts and the London School of Medicine and Dentistry 1 , 2 Newark Street, London, E1 2AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Puentes","sequence":"additional","affiliation":[{"name":"Neuroscience and Trauma Centre, Blizard Building, Institute of Cell and Molecular Medicine, Neuroimmunology Department, Barts and the London School of Medicine and Dentistry 1 , 2 Newark Street, London, E1 2AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Amor","sequence":"additional","affiliation":[{"name":"Neuroscience and Trauma Centre, Blizard Building, Institute of Cell and Molecular Medicine, Neuroimmunology Department, Barts and the London School of Medicine and Dentistry 1 , 2 Newark Street, London, E1 2AT, UK"},{"name":"Department of Pathology, VU University Medical Center 2 , De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,10,25]]},"reference":[{"key":"2022090621094342200_CIT0001","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1001\/archneur.58.3.512","article-title":"How amyotrophic lateral sclerosis got its name: the clinical-pathologic genius of Jean-Martin Charcot","volume":"58","author":"Rowland","year":"2001","journal-title":"Arch. 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