| First Author | Vidal PM | Year | 2013 |
| Journal | Cell Death Dis | Volume | 4 |
| Pages | e954 | PubMed ID | 24336074 |
| Mgi Jnum | J:316537 | Mgi Id | MGI:6837420 |
| Doi | 10.1038/cddis.2013.466 | Citation | Vidal PM, et al. (2013) ADAM17 is a survival factor for microglial cells in vitro and in vivo after spinal cord injury in mice. Cell Death Dis 4:e954 |
| abstractText | A disintegrin and metalloprotease 17 (ADAM17) is a sheddase with important substrates including tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha, 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. |
