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- W1994269551 abstract "A disintegrin and metalloprotease 17 (ADAM17) is a sheddase with important substrates including tumor necrosis factor-α (TNF-α) and its receptors, the p75 neurotrophin receptor (p75NTR), and members of the epidermal growth factor family. The rationale of this study was to inhibit ADAM17-induced shedding of soluble TNF-α in order to reduce detrimental inflammation after spinal cord injury (SCI). However, using the specific ADAM17 blocker BMS-561392 in neuronal and glial cell cultures, we show that proper functioning of ADAM17 is vital for oligodendrocyte and microglia survival in a p44 MAPK-dependent manner. In contrast, genetic ablation of ADAM17 specifically increases microglial death. Surprisingly, although blocking ADAM17 in vivo does not substantially change the ratio between membrane-bound and soluble TNF-α, it increases expression of the pro-apoptotic marker Bax and microglial apoptosis while impairing functional recovery after SCI. These data suggest that ADAM17 is a key survival factor for microglial cells after SCI." @default.
- W1994269551 created "2016-06-24" @default.
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- W1994269551 date "2013-12-12" @default.
- W1994269551 modified "2023-10-06" @default.
- W1994269551 title "ADAM17 is a survival factor for microglial cells in vitro and in vivo after spinal cord injury in mice" @default.
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- W1994269551 doi "https://doi.org/10.1038/cddis.2013.466" @default.
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