{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:48:50Z","timestamp":1785779330778,"version":"3.56.0"},"reference-count":96,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"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":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) and progressive forms of multiple sclerosis are chronic CNS diseases characterized by persistent inflammation and progressive neurodegeneration. Although triggered by distinct upstream events [persistent HTLV-1 infection in HAM\/TSP and autoimmune mechanisms in multiple sclerosis, with increasing evidence implicating Epstein\u2013Barr virus (EBV) in multiple sclerosis initiation], both conditions converge on shared inflammatory and neurodegenerative cascades.<\/jats:p>\n                  <jats:p>In HAM\/TSP, a hierarchical Tax\u2013MAP3K8\u2013MEK\u2013ERK signalling axis emerges as a proximal disease-defining pathway that promotes Th1 polarization and sustained interferon-driven inflammation, with JAK\/STAT functioning predominantly as a downstream amplification loop. Neurodegeneration in HAM\/TSP appears largely secondary to chronic virus-driven immune activation, whereas in progressive multiple sclerosis the degenerative mechanisms may evolve alongside compartmentalized, smouldering inflammation within the CNS.<\/jats:p>\n                  <jats:p>Rather than representing strictly \u2018secondary\u2019 versus \u2018primary\u2019 paradigms, both diseases are better understood along a continuum in which inflammatory, metabolic and age-related mechanisms interact to sustain axonal loss. Advanced imaging techniques reveal convergent patterns of spinal cord atrophy and microstructural injury. Biomarkers, such as proviral load and CXCL10 in HAM\/TSP and neurofilament light chain and glial fibrillary acidic protein in multiple sclerosis, provide complementary insights into inflammatory burden and neuroaxonal damage.<\/jats:p>\n                  <jats:p>Emerging therapies target immune and glial signalling pathways, including MAPK and JAK\/STAT axes, yet disease progression remains controlled only in part. By integrating hierarchical molecular signalling, viral\u2013immune interactions, imaging correlates and biomarker profiles, this review positions HAM\/TSP as a reductionist human model of chronic inflammation-driven neurodegeneration, offering translational insights relevant to progressive multiple sclerosis and other neuroinflammatory disorders.<\/jats:p>","DOI":"10.1093\/brain\/awag121","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:45:42Z","timestamp":1775130342000},"page":"2592-2603","source":"Crossref","is-referenced-by-count":0,"title":["HTLV-1-associated myelopathy as a translational model of progressive neurodegeneration"],"prefix":"10.1093","volume":"149","author":[{"given":"Marcus Tulius Teixeira","family":"da Silva","sequence":"first","affiliation":[{"name":"The Evandro Chagas\u2019 National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ) , Rio de Janeiro, RJ 21040-360 ,","place":["Brazil"]},{"name":"Complexo Hospitalar de Niter\u00f3i\/Rede Americas , Neurology Department, Niter\u00f3i, RJ 24020-096 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abelardo Q C","family":"Araujo","sequence":"additional","affiliation":[{"name":"Deolindo Couto\u2019s Institute of Neurology (INDC) and Faculty of Medicine, The Federal University of Rio de Janeiro (UFRJ) , Rio de Janeiro, RJ 22290-140 ,","place":["Brazil"]},{"name":"Postgraduate Program in Neurology and Neurosciences, Fluminense Federal University (UFF) , Niter\u00f3i, RJ 24033-900 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"2026080312474484500_awag121-B1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3389\/fmicb.2012.00388","article-title":"Epidemiological aspects and world distribution of HTLV-1 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