i(3)so3-galactosylceramide and olaparib

i(3)so3-galactosylceramide has been researched along with olaparib* in 1 studies

Other Studies

1 other study(ies) available for i(3)so3-galactosylceramide and olaparib

ArticleYear
Olaparib Attenuates Demyelination and Neuroinflammation in an Organotypic Slice Culture Model of Metachromatic Leukodystrophy.
    Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2023, Volume: 20, Issue:5

    Metachromatic leukodystrophy (MLD) is a severe demyelinating, autosomal recessive genetic leukodystrophy. The disease is underpinned by mutations in the arylsulfatase A gene (ARSA), resulting in deficient activity of the arylsulfatase A lysosomal enzyme and consequential accumulation of galactosylceramide-3-O-sulfate (sulfatide) in the brain. Using an ex vivo murine-derived organotypic cerebellar slice culture model, we demonstrate that sulfatide induces demyelination in a concentration-dependent manner. Interestingly, our novel data demonstrate that sulfatide-induced demyelination is underpinned by PARP-1 activation, oligodendrocyte loss, pro-inflammatory cytokine expression, astrogliosis, and microgliosis. Moreover, such sulfatide-induced effects can be attenuated by the treatment with the poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor Olaparib (IC50∼100 nM) suggesting that this small molecule may be neuroprotective and limit toxin-induced demyelination. Our data support the idea that sulfatide is a key driver of demyelination and neuroinflammation in MLD and suggest that PARP-1 inhibitors have therapeutic utility in the sphere of rare demyelinating disease.

    Topics: Animals; Cerebroside-Sulfatase; Demyelinating Diseases; Leukodystrophy, Metachromatic; Mice; Neuroinflammatory Diseases; Poly(ADP-ribose) Polymerase Inhibitors; Sulfoglycosphingolipids

2023