ArticleCell death & disease2016
Pharmacologic inhibition of reactive gliosis blocks TNF-α-mediated neuronal apoptosis.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
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- Brillouin microscopic assessment of retinal stiffness during reactive Müller gliosis.Experimental eye research · 2026Article
- Atypical p38 Kinase Signaling in Retinal Vascular Damage and Recovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Single-Cell Transcriptomics onBiomedicines · 2025Article
- p16-expressing microglia and endothelial cells promote tauopathy and neurovascular abnormalities in PS19 mice.Neuron · 2025Article
- Targeting Connexin 43 in Retinal Astrocytes Promotes Neuronal Survival in Glaucomatous Injury.Glia · 2025Article
- Targeting glial fibrillary acidic protein in glaucoma: a monoclonal antibody approach to modulate glial reactivity and neuroinflammation for neuroprotection.Journal of neuroinflammation · 2025Article
- Morphological Comparison of Astrocytes in the Lamina Cribrosa and Glial Lamina.Investigative ophthalmology & visual science · 2025Article
- Morphological comparison of astrocytes in the lamina cribrosa and glial lamina.bioRxiv : the preprint server for biology · 2024Article
- Lipoxins AJournal of neuroinflammation · 2024Article
- Natural Compounds Such asBiomedicines · 2022Article
- Comparative Study of the Neurotoxic Effects of Pregabalin Versus Tramadol in Rats.Neurotoxicity research · 2022Article
- Evidence of an Annexin A4 mediated plasma membrane repair response to biomechanical strain associated with glaucoma pathogenesis.Journal of cellular physiology · 2022Article
- Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation.International journal of molecular sciences · 2022Article
- Emerging Role of Neuron-Glia in Neurological Disorders: At a Glance.Oxidative medicine and cellular longevity · 2022Review
- An inducible rodent glaucoma model that exhibits gradual sustained increase in intraocular pressure with distinct inner retina and optic nerve inflammation.Scientific reports · 2021Article
- Implications of Withaferin A in neurological disorders.Neural regeneration research · 2021Article
- A novel P2X2-dependent purinergic mechanism of enteric gliosis in intestinal inflammation.EMBO molecular medicine · 2021Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
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Abstract
Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and increased polymerization of type III intermediate filaments (IFs), particularly glial fibrillary acidic protein and vimentin. However, the consequences of IF dynamics in the adult CNS remains unclear, and no pharmacologic tools have been available to target this mechanism in vivo. The mammalian retina is an accessible model to study the regulation of astrocyte stress responses, and their influence on retinal neuronal homeostasis. In particular, our work and others have implicated p38 mitogen-activated protein kinase (MAPK) signaling as a key regulator of glutamate recycling, antioxidant activity and cytokine secretion by astrocytes and related Müller glia, with potent influences on neighboring neurons. Here we report experiments with the small molecule inhibitor, withaferin A (WFA), to specifically block type III IF dynamics in vivo. WFA was administered in a model of metabolic retinal injury induced by kainic acid, and in combination with a recent model of debridement-induced astrocyte reactivity. We show that WFA specifically targets IFs and reduces astrocyte and Müller glial reactivity in vivo. Inhibition of glial IF polymerization blocked p38 MAPK-dependent secretion of TNF-α, resulting in markedly reduced neuronal apoptosis. To our knowledge this is the first study to demonstrate that pharmacologic inhibition of IF dynamics in reactive glia protects neurons in vivo.
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