Activated microglia decrease histone acetylation and Nrf2-inducible anti-oxidant defence in astrocytes: Restoring effects of inhibitors of HDACs, p38 MAPK and GSK3β
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TLDR
The study shows that well tolerated drugs such as VPA and lithium can restore an inflammatory induced depression in the Nrf2-inducible antioxidant defence, possibly via normalised histone acetylation levels.About:
This article is published in Neurobiology of Disease.The article was published on 2011-10-01 and is currently open access. It has received 84 citations till now. The article focuses on the topics: Histone deacetylase & Trichostatin A.read more
Citations
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The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Gislaine Z. Réus,Gislaine Z. Réus,Gabriel Rodrigo Fries,Laura Stertz,Marwa Badawy,Ives Cavalcante Passos,Tatiana Barichello,Flávio Kapczinski,João Quevedo +8 more
TL;DR: The role of inflammation in the pathophysiology of psychiatric disorders, such as MDD, BD, schizophrenia, and autism will be highlighted and the role of microglial activation and associated molecular cascades will be discussed as a means by which these neuroinflammatory mechanisms take place.
Journal ArticleDOI
Astrocyte Crosstalk in CNS Inflammation.
TL;DR: In this paper, the authors provide an overview of the multifaceted roles of astrocytes in the context of CNS inflammation and neurodegeneration, and explore mechanisms of crosstalk between cells in the central nervous system (CNS) and discuss how these interactions shape pathological outcomes.
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NRF2-regulation in brain health and disease: implication of cerebral inflammation.
TL;DR: The hypothesis that inflammation via prolonged activation of key kinases (p38 and GSK-3β and activation of histone deacetylases gives rise to dysregulation of the NRF2 system in the brain, which contributes to oxidative stress and injury is brought forward.
Journal ArticleDOI
New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates—Nrf2 activators and GSK-3 inhibitors
Michael Maes,Zdenĕk Fisar,Miguel Medina,Giovanni Scapagnini,Gabriel Nowak,Michael Berk,Michael Berk +6 more
TL;DR: These six pathways offer new, pathophysiologically guided drug targets suggesting that novel therapies could be developed that target these six pathways simultaneously and both nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activators and glycogen synthase kinase-3 (GSK-3) inhibitors target the six above-mentioned pathways.
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Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications.
Qingzheng Kang,Chunxue Yang +1 more
TL;DR: The abnormalities correlated with oxidative stress provide multiple potential therapeutic targets to develop safe and effective treatments for diabetic retinopathy and are summarized.
References
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Journal ArticleDOI
Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation.
TL;DR: The Nrf2-Keap1 system is present not only in mammals, but in fish, suggesting that its roles in cellular defense are conserved throughout evolution among vertebrates.
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Glutathione dysregulation and the etiology and progression of human diseases.
Nazzareno Ballatori,Suzanne M. Krance,Sylvia Notenboom,Shujie Shi,Kim Tieu,Christine L. Hammond +5 more
TL;DR: The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases and suggests the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment.
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Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1.
Akira Kobayashi,Moon Il Kang,Yoriko Watai,Kit I. Tong,Takahiro Shibata,Koji Uchida,Masayuki Yamamoto +6 more
TL;DR: The contention that Nrf2 protein synthesized de novo after exposure to stress accumulates in the nucleus by bypassing the Keap1 gate supports the contention that the sensory mechanism of oxidative and electrophilic stresses is closely linked to the degradation mechanism of NRF2.
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SCF/{beta}-TrCP promotes glycogen synthase kinase 3-dependent degradation of the Nrf2 transcription factor in a Keap1-independent manner.
TL;DR: This work phosphorylates a group of Ser residues in the Neh6 domain of mouse Nrf2 that overlap with an SCF/β-TrCP destruction motif (DSGIS, residues 334 to 338) and promotes its degradation in a Keap1-independent manner, and proposes a “dual degradation” model to describe the regulation of NRF2 under different pathophysiological conditions.
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Expression of Nrf2 in Neurodegenerative Diseases
Chenere P. Ramsey,Charles A. Glass,Marshall B. Montgomery,Kathryn A. Lindl,Gillian P. Ritson,Luis A. Chia,Ronald L. Hamilton,Charleen T. Chu,Kelly L. Jordan-Sciutto +8 more
TL;DR: It is suggested that Nrf2-mediated transcription is not induced in neurons in AD despite the presence of oxidative stress, and in PD, nuclear localization of NRF2 is strongly induced, but this response may be insufficient to protect neurons from degeneration.
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