Downregulation of the deubiquitinating enzyme USP10 correlates with neuronal apoptosis in HTLV-1-associated myelopathy

去泛素化酶USP10的下调与HTLV-1相关性脊髓病中的神经元凋亡相关。

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Abstract

Human T-cell leukemia virus type 1–associated myelopathy (HAM) is a chronic neuroinflammatory disease characterized by spinal cord neuronal loss. The mechanisms underlying this degeneration remain unclear. We investigated the role of ubiquitin-specific peptidase 10 (USP10), a regulator of oxidative stress and apoptosis, in HAM pathogenesis. Spinal cord tissues from eight HAM patients and two healthy controls (HCs) were analyzed by immunohistochemistry. We assessed USP10 expression, neuronal density (NeuN), apoptotic markers (TUNEL, active caspase-3), and p62, a stress-responsive regulator of autophagy and apoptosis. USP10 expression was markedly reduced in HAM neurons compared to HCs. This downregulation was associated with increased neuronal apoptosis and decreased NeuN-positive cell density, particularly among large neurons, and some surviving neurons showed diminished NeuN immunoreactivity. Reduced p62 expression was also observed in cases with low USP10 and high apoptotic activity. Notably, one HAM patient with preserved USP10 and p62 expression exhibited minimal neuronal loss and mild neurological symptoms. Although exploratory, this study supports an association between downregulation of USP10 and reduced p62 levels, and neuronal apoptosis and loss in HAM, and highlights USP10 as a potential regulator of neuronal survival, and a promising diagnostic or prognostic marker and a future therapeutic pathway in virus-induced neuroinflammation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-37271-x.

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