Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Javier PalazuelosAdan Aguirre

Abstract

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 inte...Continue Reading

Citations

Jun 27, 2019·Cellular and Molecular Life Sciences : CMLS·Hung-En HsiaStefan F Lichtenthaler
Nov 20, 2016·Annual Review of Medicine·Mark Bothwell
Jul 4, 2021·British Journal of Pharmacology·Tania AguadoJavier Palazuelos
Oct 7, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Johanna TüshausStefan F Lichtenthaler

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