RT Journal Article
T1 Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17
A1 Palazuelos Diego, Javier
A1 Klingener, Michael
A1 Raines, Elaine
A1 Crawford, Howard
A1 Aguirre, Adan
AB The identification of the molecular network that supports oligodendrocyte (OL) regeneration under demyelinating conditions has been a primary goal for regenerative medicine in demyelinating disorders. We recently described an essential function for TACE/ADAM17 in regulating oligodendrogenesis during postnatal myelination, but it is unknown whether this protein also plays a role in OL regeneration and remyelination under demyelinating conditions. By using genetic mouse models to achieve selective gain- or loss-of-function of TACE or EGFR in OL lineage cells in vivo, we found that TACE is critical for EGFR activation in OLs following demyelination, and therefore, for sustaining OL regeneration and CNS remyelination. TACE deficiency in oligodendrocyte progenitor cells following demyelination disturbs OL lineage cell expansion and survival, leading to a delay in the remyelination process. EGFR overexpression in TACE deficient OLs in vivo restores OL development and postnatal CNS myelination, but also OL regeneration and CNS remyelination following demyelination. Our study reveals an essential function of TACE in supporting OL regeneration and CNS remyelination that may contribute to the design of new strategies for therapeutic intervention in demyelinating disorders by promoting oligodendrocyte regeneration and myelin repair.
PB Society for Neuroscience
SN 0270-6474
YR 2015
FD 2015
LK https://hdl.handle.net/20.500.14352/89021
UL https://hdl.handle.net/20.500.14352/89021
LA eng
NO Palazuelos, Javier, et al. «Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17». The Journal of Neuroscience, vol. 35, n.o 35, septiembre de 2015, pp. 12241-47. https://doi.org/10.1523/JNEUROSCI.3937-14.2015.
NO National Institutes of Health
NO National Multiple Sclerosis Society
DS Docta Complutense
RD 28 abr 2025