Pregled bibliografske jedinice broj: 1104306
Immunity in amyotrophic lateral sclerosis: blurred lines between excessive inflammation and inefficient immune responses
Immunity in amyotrophic lateral sclerosis: blurred lines between excessive inflammation and inefficient immune responses // Brain Communications, 2 (2020), 2; 1-26 doi:10.1093/braincomms/fcaa124 (međunarodna recenzija, pregledni rad, znanstveni)
CROSBI ID: 1104306 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Immunity in amyotrophic lateral sclerosis: blurred lines between excessive inflammation and inefficient
immune responses
(Immunity in amyotrophic lateral sclerosis: blurred lines between excessive inflammation and inefficient immune
responses)
Autori
Béland, Louis-Charles ; Markovinović, Andrea ; Jakovac, Hrvoje ; De Marchi, Fabiola ; Bilić, Ervina ; Mazzini, Letizia ; Križ, Jasna ; Munitić, Ivana
Izvornik
Brain Communications (2632-1297) 2
(2020), 2;
1-26
Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni
Ključne riječi
amyotrophic lateral sclerosis ; neuroinflammation ; neuroimmunity neurodegeneration ; immunodeficiency
Sažetak
Despite wide genetic, environmental and clinical heterogeneity in amyotrophic lateral sclerosis, a rapidly fatal neurodegenerative disease targeting motoneurons, neuroinflammation is a common finding. It is marked by local glial activation, T cell infiltration and systemic immune system activation. The immune system has a prominent role in the pathogenesis of various chronic diseases, hence some of them, including some types of cancer, are successfully targeted by immunotherapeutic approaches. However, various anti-inflammatory or immunosuppressive therapies in amyotrophic lateral sclerosis have failed. This prompted increased scrutiny over the immune- mediated processes underlying amyotrophic lateral sclerosis. Perhaps the biggest conundrum is that amyotrophic lateral sclerosis pathogenesis exhibits features of three otherwise distinct immune dysfunctions—excessive inflammation, autoimmunity and inefficient immune responses. Epidemiological and genome-wide association studies show only minimal overlap between amyotrophic lateral sclerosis and autoimmune diseases, so excessive inflammation is usually thought to be secondary to protein aggregation, mitochondrial damage or other stresses. In contrast, several recently characterized amyotrophic lateral scler- osis-linked mutations, including those in TBK1, OPTN, CYLD and C9orf72, could lead to inefficient immune responses and/or damage pile-up, suggesting that an innate immunodeficiency may also be a trigger and/or modifier of this disease. In such cases, non- selective immunosuppression would further restrict neuroprotective immune responses. Here we discuss multiple layers of im- mune-mediated neuroprotection and neurotoxicity in amyotrophic lateral sclerosis. Particular focus is placed on individual patient mutations that directly or indirectly affect the immune system, and the mechanisms by which these mutations influence disease pro- gression. The topic of immunity in amyotrophic lateral sclerosis is timely and relevant, because it is one of the few common and potentially malleable denominators in this heterogenous disease. Importantly, amyotrophic lateral sclerosis progression has recently been intricately linked to patient T cell and monocyte profiles, as well as polymorphisms in cytokine and chemokine receptors. For this reason, precise patient stratification based on immunophenotyping will be crucial for efficient therapies.
Izvorni jezik
Engleski
Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)
POVEZANOST RADA
Projekti:
HRZZ-IP-2018-01-8563 - Kontrola neurodegeneracije moduliranjem sprege između upale i proteinopatije (ImmunoModifyCNS) (Munitić, Ivana, HRZZ - 2018-01) ( CroRIS)
HRZZ-UIP-2013-11-7459 - Istraživanje uloge optineurina u neuroprotekciji (OptineurinNeuroimm) (Munitić, Ivana, HRZZ - 2013-11) ( CroRIS)
Ustanove:
Medicinski fakultet, Rijeka,
Medicinski fakultet, Zagreb,
Klinički bolnički centar Zagreb,
Sveučilište u Rijeci - Odjel za biotehnologiju
Profili:
Hrvoje Jakovac
(autor)
Ervina Bilić
(autor)
Andrea Markovinović
(autor)
Jasna Križ
(autor)
Ivana Munitić
(autor)