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Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia [ChIP-seq]

ABSTRACT: Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia [ChIP-seq]

PROVIDER: PRJNA1043663 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26902432.fastq.gz	Fastqsanger.gz
	SRR26902433.fastq.gz	Fastqsanger.gz

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Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia

Project description:Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia

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Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia [RNA-seq]

Project description:Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remains largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. We identified Prmt5 as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo. Prmt5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that Prmt5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, we treated mice with middle cerebral artery occlusion (MCAO) with the Prmt5 inhibitor EPZ015666 and found that Prmt5 inhibition sustain protection against neuronal death in vivo. Together, our findings revealed a novel epigenetic mechanism of Prmt5 in cerebral ischemia and uncovered a potential target for neuroprotection.

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Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia [ChIP-seq]

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Project description:Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia [RNA-seq]

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Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:Cerebral ischemia, commonly resulting from an ischemic stroke, can lead to significant cognitive impairments due to neuronal damage and neuroinflammation. The cannabinoid CB1 receptor, part of the endocannabinoid system, plays a crucial role in modulating synaptic plasticity, neurogenesis, and neuroprotection. Research suggests that targeting the CB1 receptor could offer a promising therapeutic strategy to mitigate cognitive deficits following cerebral ischemia. Modulating CB1 receptor activity, either through agonists or antagonists, has been shown to influence key pathways involved in neuroprotection and inflammation, potentially enhancing recovery of cognitive functions. Understanding the mechanisms by which CB1 receptor modulation affects brain recovery post-ischemia could pave the way for novel treatments aimed at reducing the long-term cognitive impact of ischemic strokes.

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