Dataset Information

Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke.

ABSTRACT: Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy. Even so, patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury. It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies. Regarding the pathogenesis, multiple pathological events trigger the activation of cell death pathways. Particular attention should be devoted to excitotoxicity, oxidative stress, and inflammatory responses. Thus, in this article, we first review the principal mechanisms underlying neuronal death mediated by these significant events, such as intrinsic and extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, and autophagic cell death. Then, we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.

SUBMITTER: Mao R

PROVIDER: S-EPMC9554175 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke.

Mao Rui R Zong Ningning N Hu Yujie Y Chen Ying Y Xu Yun Y

Neuroscience bulletin 20220505 10

Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy. Even so, patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury. It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in or ...[more]

PMID: 35513682

Similar Datasets

Project description:Background and objectiveStroke poses a critical health issue without effective neuroprotection. We explore ischemic postconditioning's (IPostC) potential to mitigate stroke-induced brain injury, focusing on its interaction with disulfidptosis, a novel cell death pathway marked by protein disulfide accumulation. We aim to clarify IPostC's protective mechanisms against stroke through gene sequencing and experimental analysis in mice.MethodsThrough our initial investigation, we identified 27 disulfidptosis-related genes (DRGs) and uncovered their interactions. Additionally, differential gene analysis revealed 11 potential candidate genes that are linked to disulfidptosis, stroke, and IPostC. Our comprehensive study employed various analytical approaches, including machine learning, functional enrichment analysis, immune analysis, drug sensitivity analysis, and qPCR experiments, to gain insights into the molecular mechanisms underlying these processes.ResultsOur study identified and expanded the list of disulfidptosis-related genes (DRGs) critical to stroke, revealing key genes and their interactions. Through bioinformatics analyses, including PCA, UMAP, and differential gene expression, we were able to differentiate the effects of stroke from those of postconditioning, identifying Peroxiredoxin 1 (PRDX1) as a key gene of interest. GSEA highlighted PRDX1's involvement in protective pathways against ischemic damage, while its correlations with various proteins suggest a broad impact on stroke pathology. Constructing a ceRNA network and analyzing drug sensitivities, we explored PRDX1's regulatory mechanisms, proposing novel therapeutic avenues. Additionally, our immune infiltration analysis linked PRDX1 to key immune cells, underscoring its dual role in stroke progression and recovery. PRDX1 is identified as a key target in ischemic stroke based on colocalization analysis, which revealed that PRDX1 and ischemic stroke share the causal variant rs17522918. The causal relationship between PRDX1-related methylation sites (cg02631906 and cg08483560) and the risk of ischemic stroke further validates PRDX1 as a crucial target.ConclusionsThese results suggest that the DRGs are interconnected with various cell death pathways and immune processes, potentially contributing to IPostC regulating cell death mechanisms in stroke.

Dataset Information

Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke.

Publications

Neuronal Death Mechanisms and Therapeutic Strategy in Ischemic Stroke.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets