ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2023
Elucidating the Therapeutic Utility of Olaparib in Sulfatide-Induced Human Astrocyte Toxicity and Neuroinflammation.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 3 citations in OpenAlex.
- PARP1 rewires neuroinflammatory and redox metabolism associated with reactive neuroglia in neuropathic pain.Redox biology · 2026Article
- Olaparib alleviates diclofenac-induced toxicity in HepG2 cells via modulation of oxidative stress and mitochondrial functions.Molecular and cellular biochemistry · 2026Article
- Deferiprone protects against photoreceptor degeneration by inhibiting parthanatos.Cell death & disease · 2025Article
- The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders.Antioxidants (Basel, Switzerland) · 2024Review
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3 authors at 1 institution in 1 country.
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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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