Artikel ; Online: Elucidating the Therapeutic Utility of Olaparib in Sulfatide-Induced Human Astrocyte Toxicity and Neuroinflammation.
2023 Band 18, Heft 4, Seite(n) 592–609
Abstract: Metachromatic leukodystrophy (MLD) is a severe demyelinating, autosomal recessive genetic leukodystrophy, with no curative treatment. The disease is underpinned by mutations in the arylsulfatase A gene (ARSA), resulting in deficient activity of this ... ...
Abstract | Metachromatic leukodystrophy (MLD) is a severe demyelinating, autosomal recessive genetic leukodystrophy, with no curative treatment. The disease is underpinned by mutations in the arylsulfatase A gene (ARSA), resulting in deficient activity of this lysosomal enzyme, and consequential accumulation of galactosylceramide-3-O-sulfate (sulfatide) in the brain. Most of the effects in the brain have been attributed to the accumulation of sulfatides in oligodendrocytes and their cell damage. In contrast, less is known regarding sulfatide toxicity in astrocytes. Poly (ADP-ribose) polymerase (PARP) inhibitors are anti-cancer therapeutics that have proven efficacy in preclinical models of many neurodegenerative and inflammatory diseases, but have never been tested for MLD. Here, we examined the toxic effect of sulfatides on human astrocytes and restoration of this cell damage by the marketed PARP-1 inhibitor, Olaparib. Cultured human astrocytes were treated with increasing concentrations of sulfatides (5-100 μM) with or without Olaparib (100 nM). Cell viability assays were used to ascertain whether sulfatide-induced toxicity was rescued by Olaparib. Immunofluorescence, calcium (Ca |
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Mesh-Begriff(e) | Humans ; Sulfoglycosphingolipids ; Astrocytes ; Neuroinflammatory Diseases ; Poly(ADP-ribose) Polymerase Inhibitors/toxicity ; Reactive Oxygen Species ; Leukodystrophy, Metachromatic/genetics ; Leukodystrophy, Metachromatic/therapy |
Chemische Substanzen | Sulfoglycosphingolipids ; olaparib (WOH1JD9AR8) ; Poly(ADP-ribose) Polymerase Inhibitors ; Reactive Oxygen Species |
Sprache | Englisch |
Erscheinungsdatum | 2023-11-04 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2227405-4 |
ISSN | 1557-1904 ; 1557-1890 |
ISSN (online) | 1557-1904 |
ISSN | 1557-1890 |
DOI | 10.1007/s11481-023-10092-9 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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