ADAM17 - A key regulator of microglia polarization after spinal cordinjury (R-6399)

Spinal cord injury (SCI) is characterized by strong post-traumatic inflammation including proinflammatory M1 microglia activation. However, recent studies revealed that activated microglia can also adopt a pro-regenerative phenotype (M2) and improve neural regeneration. Hence, targeting the microglia phenotype M1/M2 switch after SCI is a very promising therapeutic strategy. Preliminary data from our group indicate that "a disintegrin and metalloproteinase 17" (ADAM17) is a key regulator of the microglial phenotype. ADAM17-deficient primary microglia cultures have a high tendency to acquire an M2 phenotype. Moreover, ADAM17-deficient mice showed improved functional outcome after SCI. Based on these findings, we hypothesize that ADAM17 is a major regulator driving activated microglia towards a pro-inflammatory M1 phenotype. Furthermore, we assume that the inhibition of ADAM17 favors neuroregeneration after SCI. We will characterize the key domains of ADAM17 and the involved signaling pathways, by which the microglia phenotypic switch is induced. These insights in ADAM17 signaling may lead to new therapeutic approaches for central nervous system trauma.

Keywords:SPINAL CORD INJURY

Disciplines:Morphological sciences