{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T10:46:07Z","timestamp":1772793967188,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,5]],"date-time":"2016-04-05T00:00:00Z","timestamp":1459814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UCLH\/UCL"},{"name":"Department of Health's NIHR Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Huntington's disease (HD) is a neurodegenerative condition characterized by pathology in the brain and peripheral tissues. Hyperactivity of the innate immune system, due in part to NF\u03baB pathway dysregulation, is an early and active component of HD. Evidence suggests targeting immune disruption may slow disease progression. Laquinimod is an orally active immunomodulator that down\u2010regulates proinflammatory cytokine production in peripheral blood mononuclear cells, and in the brain down\u2010regulates astrocytic and microglial activation by modulating NF\u03baB signalling. Laquinimod had beneficial effects on inflammation, brain atrophy and disease progression in multiple sclerosis (MS) in two phase III clinical trials. This study investigated the effects of laquinimod on hyperactive proinflammatory cytokine release and NF\u03baB signalling in HD patient myeloid cell cultures. Monocytes from manifest (manHD) and pre\u2010manifest (preHD) HD gene carriers and healthy volunteers (HV) were treated with laquinimod and stimulated with lipopolysaccharide. After 24\u00a0h pre\u2010treatment with 5\u00a0\u03bcM laquinimod, manHD monocytes released lower levels of IL\u20101\u03b2, IL\u20105, IL\u20108, IL\u201010, IL\u201013 and TNF\u03b1 in response to stimulation. PreHD monocytes released lower levels of IL\u20108, IL\u201010 and IL\u201013, with no reduction observed in HV monocytes. The effects of laquinimod on dysfunctional NF\u03baB signalling in HD was assessed by inhibitor of kappa B (I\u03baB) degradation kinetics, nuclear translocation of NF\u03baB and interactions between I\u03baB kinase (IKK) and HTT, in HD myeloid cells. No differences were observed between laquinimod\u2010treated and untreated conditions. These results provide evidence that laquinimod dampens hyper\u2010reactive cytokine release from manHD and preHD monocytes, with a much reduced effect on HV monocytes.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13553-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nEvidence suggests targeting CNS and peripheral immune disruption may slow Huntington's disease (HD) neurodegenerative processes. The effects of laquinimod, an orally active immunomodulator, on hyperactive cytokine release and dysfunctional NF\u03baB signalling in stimulated myeloid cell cultures from pre\u2010manifest and manifest HD gene carriers and healthy volunteers were investigated. Laquinimod dampened cytokine release but did not impact NF\u03baB signalling.<\/jats:p><jats:p>Read the <jats:bold>Editorial Highlight<\/jats:bold> for this article on page <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/jnc.13539\">670<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13553","type":"journal-article","created":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T07:01:09Z","timestamp":1454050869000},"page":"782-794","source":"Crossref","is-referenced-by-count":34,"title":["Laquinimod dampens hyperactive cytokine production in Huntington's disease patient myeloid cells"],"prefix":"10.1111","volume":"137","author":[{"given":"Lucianne","family":"Dobson","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Diseases University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery London 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