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HTLV1-associated myelopathy as a translational model of progressive neurodegeneration - PubMed

5 hours ago
  • #HAM/TSP
  • #progressive multiple sclerosis
  • #neurodegeneration
  • HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and progressive multiple sclerosis (MS) are chronic CNS diseases with persistent inflammation and progressive neurodegeneration.
  • HAM/TSP is driven by persistent HTLV-1 infection, while progressive MS involves autoimmune mechanisms, possibly initiated by Epstein-Barr virus (EBV).
  • Both conditions converge on shared inflammatory and neurodegenerative pathways, with HAM/TSP featuring a hierarchical Tax-MAP3K8-MEK-ERK signaling axis that promotes Th1 polarization and interferon-driven inflammation.
  • Neurodegeneration in HAM/TSP is largely secondary to chronic immune activation, whereas in progressive MS, degenerative mechanisms may evolve alongside smouldering CNS inflammation.
  • Advanced imaging shows convergent patterns of spinal cord atrophy and microstructural injury in both diseases.
  • Biomarkers like proviral load and CXCL10 in HAM/TSP, and neurofilament light chain and GFAP in MS, provide insights into inflammatory burden and neuroaxonal damage.
  • Emerging therapies target immune and glial signaling pathways, including MAPK and JAK/STAT axes, but disease progression remains only partially controlled.
  • The review positions HAM/TSP as a translational model for understanding chronic inflammation-driven neurodegeneration, relevant to progressive MS and other neuroinflammatory disorders.