RT Journal Article T1 Tumor Necrosis Factor (TNF)-α-Stimulated Gene 6 (TSG-6): A Promising Immunomodulatory Target in Acute Neurodegenerative Diseases A1 La Russa, Daniele A1 Di Santo, Chiara A1 Lizasoaín Hernández, Ignacio A1 Moraga Yébenes, Ana A1 Bagetta, Giacinto A1 Amantea, Diana AB Tumor necrosis factor (TNF)-α-stimulated gene 6 (TSG-6), the first soluble chemokine-binding protein to be identified in mammals, inhibits chemotaxis and transendothelial migration of neutrophils and attenuates the inflammatory response of dendritic cells, macrophages, monocytes, and T cells. This immunoregulatory protein is a pivotal mediator of the therapeutic efficacy of mesenchymal stem/stromal cells (MSC) in diverse pathological conditions, including neuroinflammation. However, TSG-6 is also constitutively expressed in some tissues, such as the brain and spinal cord, and is generally upregulated in response to inflammation in monocytes/macrophages, dendritic cells, astrocytes, vascular smooth muscle cells and fibroblasts. Due to its ability to modulate sterile inflammation, TSG-6 exerts protective effects in diverse degenerative and inflammatory diseases, including brain disorders. Emerging evidence provides insights into the potential use of TSG-6 as a peripheral diagnostic and/or prognostic biomarker, especially in the context of ischemic stroke, whereby the pathobiological relevance of this protein has also been demonstrated in patients. Thus, in this review, we will discuss the most recent data on the involvement of TSG-6 in neurodegenerative diseases, particularly focusing on relevant anti-inflammatory and immunomodulatory functions. Furthermore, we will examine evidence suggesting novel therapeutic opportunities that can be afforded by modulating TSG-6-related pathways in neuropathological contexts and, most notably, in stroke. PB MDPI SN 1422-0067 YR 2023 FD 2023-01-06 LK https://hdl.handle.net/20.500.14352/104926 UL https://hdl.handle.net/20.500.14352/104926 LA eng NO La Russa, D.; Di Santo, C.; Lizasoain, I.; Moraga, A.; Bagetta, G.; Amantea, D. Tumor Necrosis Factor (TNF)-α-Stimulated Gene 6 (TSG-6): A Promising Immunomodulatory Target in Acute Neurodegenerative Diseases. Int. J. Mol. Sci. 2023, 24, 1162. https://doi.org/10.3390/ijms24021162 NO Ministerio de educación, universidades e investigación (Italia) DS Docta Complutense RD 7 abr 2025