Ischemic insults induce necroptotic cell death in hippocampal neurons through the up-regulation of endogenous RIP3

Vieira, Marta; Fernandes, Júlia; Carreto, Laura; Anuncibay‐Soto, Berta; Santos, Manuel A. S.; Han, Jiahuai; Fernández‐López, Arsenio; Duarte, Carlos B.; Carvalho, Ana Luı́sa; Santos, Ana Lúcia

doi:10.1016/j.nbd.2014.04.002

Cited by 113 publications

(95 citation statements)

References 65 publications

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“…The necroptosis specific inhibitor, necrostatin-1 (Nec-1), significantly decreased the volume of brain infarction and improved the behavior of mice when administered 2 or 6 h following MCAO (9). Similar results were also detected in cultured hippocampal neurons following oxygen-glucose deprivation (OGD), an ischemia-reperfusion model (11). Inhibiting necroptosis significantly decreases the OGD-induced loss of cultured hippocampal neurons (11), suggesting that necroptosis is important in ischemia-reperfusion damage.…”

Section: Introductionsupporting

confidence: 67%

“…Similar results were also detected in cultured hippocampal neurons following oxygen-glucose deprivation (OGD), an ischemia-reperfusion model (11). Inhibiting necroptosis significantly decreases the OGD-induced loss of cultured hippocampal neurons (11), suggesting that necroptosis is important in ischemia-reperfusion damage. Additional studies have revealed that receptor-interacting protein (RIP)1, RIP3 and ROS are important signaling molecules in necropolis (11,12).…”

Section: Introductionsupporting

confidence: 67%

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Inhibiting histone deacetylase 6 partly protects cultured rat cortical neurons from oxygen-glucose deprivation-induced necroptosis

Yuan

Wang

Liu

et al. 2015

Molecular Medicine Reports

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Necroptosis has an important role in ischemia-reperfusion damage. The expression of histone deacetylase 6 (HDAC6) is upregulated in neurons following ischemia-reperfusion, however, whether HDAC6 is closely involved in the necroptosis, which occurs during ischemia-reperfusion damage remains to be elucidated. In the present study, the roles of HDAC6 in the necroptosis of cultured rat cortical neurons were investigated in a oxygen-glucose deprivation (OGD) model. The results demonstrated that OGD induced marked necroptosis of cultured rat cortical neurons and upregulated the expression of HDAC6 in the cultured neurons, compared with the control (P<0.05). The necroptosis inhibitor, necrostatin-1 (Nec-1), decreased The expression of HDAC6 in the OGD-treated cultured neurons, accompanied by the inhibition of necroptosis. Further investigation revealed that, compared with OGD treatment alone, inhibiting the activity of HDAC6 with tubacin, a specific HDAC6 inhibitor, reduced the OGD-induced necroptosis of the cultured rat cortical neurons (P<0.05), which was similar to the change following treatment with Nec-1 (P>0.05). In addition, inhibiting the activity of HDAC6 reversed the OGD-induced increase of reactive oxygen species (ROS) and the OGD-induced decrease of acetylated tubulin in the cultured rat cortical neurons (P<0.05), compared with the neurons treated with OGD alone). The levels of acetylated tubulin in the cultured neurons following treatment with OGD and tubacin were significantly higher than those in the control (P<0.05). These results suggested that HDAC6 was involved in the necroptosis of neurons during ischemia-reperfusion by modulating the levels of ROS and acetylated tubulin.

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Section: Introductionsupporting

confidence: 67%

Section: Introductionsupporting

confidence: 67%

Inhibiting histone deacetylase 6 partly protects cultured rat cortical neurons from oxygen-glucose deprivation-induced necroptosis

Yuan

Wang

Liu

et al. 2015

Molecular Medicine Reports

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“…However, research on this pathway remains rather limited in CNS conditions. In primary hippocampal neurons, necroptosis was induced via RIP3 upon an ischemic insult [49]. Moreover, it was recently shown in vivo in mice that intracerebroventricular injection with TNF-α caused RIP3-mediated necroptosis of hippocampal neurons [50].…”

Section: Tnf-α Receptor 1 Signalingmentioning

confidence: 99%

Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

et al. 2015

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Numerous studies have revealed the pleiotropic functions of tumor necrosis factor alpha (TNF-α), and have linked it with several neurodegenerative disorders. This review describes the signaling pathways induced by TNF-α via its two receptors (TNFR1 and TNFR2), and their functions in neurodegenerative processes as in Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and ischemic stroke. It has become clear that TNF-α may exert divergent actions in neurodegenerative disorders, including neurodegenerative and neuroprotective effects, which appear to depend on its signaling via either TNFR1 or TNFR2. Specific targeting of these receptors is a promising therapeutic strategy for many disorders.

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“…While both necrosis and necroptosis prevalently occur in acute brain injuries, such as ischemic damage [6], there is little doubt that apoptosis plays a major role in neurodegenerative diseases [7].…”

Section: Introductionmentioning

confidence: 99%

Drug target identification at the crossroad of neuronal apoptosis and survival

Maino

Paparone

Severini

et al. 2017

Expert Opinion on Drug Discovery

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Introduction: Inappropriate activation of apoptosis may contribute to neurodegeneration, a multifaceted process that results in various chronic disorders, including Alzheimer's and Parkinson's diseases. Several in vitro and in vivo studies demonstrated that neuronal apoptosis is a multi-pathway cell-death program that requires RNA synthesis. Thus, transcriptionally activated genes whose products induce cell death can be triggered by different stimuli and antagonized by neurotrophic factors. Systems biology is now unveiling the series of intracellular signaling pathways and key drug targets at the intersection of neuronal apoptosis and survival. Areas covered: This review introduces a genomic approach that can be used to elucidate the systems biology of neuronal apoptosis and survival, and to rationally select drug targets, no longer oriented to emulate the action of growth factors at the membrane receptor level, but rather to modulate their downstream signals. Expert opinion: The advent of genomics is offering an unprecedented opportunity to explore how the delicate balance between apoptosis and survival-inducing signals triggers a transcriptional program. Characterization of this program can be useful to identify potential pharmacological targets for existing drugs. Such knowledge might pave the way towards an innovative pharmacology. ARTICLE HISTORY

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Ischemic insults induce necroptotic cell death in hippocampal neurons through the up-regulation of endogenous RIP3

Cited by 113 publications

References 65 publications

Inhibiting histone deacetylase 6 partly protects cultured rat cortical neurons from oxygen-glucose deprivation-induced necroptosis

Inhibiting histone deacetylase 6 partly protects cultured rat cortical neurons from oxygen-glucose deprivation-induced necroptosis

Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

Drug target identification at the crossroad of neuronal apoptosis and survival

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