TNF-alpha converting enzyme (TACE) is a major survival factor after CNS trauma (R-4209)

A mounting body of evidence suggests that inflammation not only damages but also contributes to regeneration after central nervous system (CNS) trauma. We have previously shown that not only anti-inflammatory cytokines, such as interleukin-4 (IL-4), promote regeneration and functional recovery after spinal cord injury (SCI), but that pro inflammatory cytokines (e.g. IL-1beta and tumor necrosis factor-alfa (TNF-alfa)) also stimulate neurite growth in vitro. Conflicting data suggest influencing TNF-alfa signaling can be both detrimental and beneficial for recovery after SCI, which depends in part on the timing of treatment. We have blocked TNF-alfa signaling in the chronic phase after SCI by using etanercept, but found it to be ineffective in promoting recovery. In contrast, preliminary data of our group show that TNF-alfa-converting enzyme (TACE) is protective after SCI, since blocking the release of soluble TNF-alfa by inhibiting TACE worsens functional outcome after SCI; moreover, using cell lines, survival of oligodendrocytes and microglia seems to be impaired by TACE inhibition. Based on these findings, we hypothesize that TACE is a major neuroprotective and pro-regenerative factor that promotes recovery from CNS trauma. Elucidating the mechanisms (downstream molecules) by which TACE exerts these effects will lead to new insights in TACE signaling in SCI, thereby possibly generating new diagnostic and therapeutic approaches for CNS trauma.

Keywords:SPINAL CORD INJURY

Disciplines:Systems biology