<scp>FOXO4</scp> alleviates hippocampal neuronal damage in epileptic mice via the <scp>miR</scp>‐138‐5p/<scp>ROCK2</scp> axis

Jin, Xin; Liao, Xingjuan; Wu, Longfei; Huang, Jian; Li, Zhimin; Li, Yali; Guo, Fan

doi:10.1002/ajmg.b.32904

Cited by 3 publications

(1 citation statement)

References 59 publications

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“…117 The Rho/(ROCK pathway may also contribute to neuronal damage, oxidative stress, and neuroinflammation in epilepsy. 96,118 ROCK2 expression in the hippocampus is upregulated in patients with temporal lobe epilepsy and may contribute to drug resistance by promoting astrogliosis. 119 Excessive ROCK activation may also predispose to excitotoxicity in the setting of seizures; ROCK inhibition protects against kainic acid-induced neuronal death.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

What Is the Role of the Rho-ROCK Pathway in Neurologic Disorders?

Benarroch

2023

Neurology

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Rho-associated coiled-coil containing kinases (ROCK), including ROCK1 and ROCK2, are the primary effectors of the Rho family of small guanosine triphosphatases (GTPases)1 (Figure). The Rho/ROCK signaling pathway has a critical role in regulating the cytoskeleton dynamics responsible for cell adhesion, proliferation, motility, and contraction.2,3 In the nervous system, ROCK proteins phosphorylate a wide variety of transduction molecules that regulate axonal growth during development and after injury; dendritic growth and spine remodeling underlying synaptic plasticity; cell survival through cross talk with other signal transduction pathways; and glial activation and function, including neuroinflammation.4-7 Experimental studies using ROCK antagonists or RNA interference approaches indicate that Rho/ROCK signaling may have a major role in the pathogenesis of a wide range of neurologic and non-neurologic disorders. Not surprisingly, ROCK inhibition has been extensively explored as an emerging therapeutic target in several disease models. There are several comprehensive reviews on these topics.2,3,8-14 Some of the basic concepts on Rho/ROCK signaling, its effects in the nervous system, and its potential implications in the pathogenesis and as a therapeutic target in neurologic disorders, will be briefly emphasized in this study.

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Section: Neurodegenerative Diseasesmentioning

confidence: 99%

What Is the Role of the Rho-ROCK Pathway in Neurologic Disorders?

Benarroch

2023

Neurology

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Identification of candidate biomarkers and signaling pathways associated with Alzheimer’s disease using bioinformatics analysis of next generation sequencing data

Vastrad,

Vastrad

2024

Preprint

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Alzheimer's disease (AD) is the most common cause of dementia, and one of the most common health problems all over the world. However, the specific molecular mechanisms of AD have not been fully investigated. The current investigation aimed to elucidate potential key candidate genes and signaling pathways in AD. Next generation sequencing (NGS) dataset GSE203206 was downloaded from the Gene Expression Omnibus (GEO) database, which included data from 39 AD samples and 8 normal control samples. Differentially expressed genes (DEGs) were identified using t-tests in the limma R bioconductor package. These DEGs were subsequently investigated by Gene ontology (GO) and pathway enrichment analysis, and a protein-protein interaction (PPI) network and modules were constructed and analyzed. The miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were performed to identify key miRNAs and TFs. The receiver operating characteristic (ROC) curve analysis was performed to estimate the clinical diagnostic value of the hub genes. A total of 958 DEGs, including 479 up regulated genes and 479 down regulated genes, were screened between AD and normal control samples. GO and pathway enrichment analysis results revealed that the up regulated genes were mainly enriched in response to stimulus, cytoplasm, small molecule binding and signal transduction, whereas down regulated genes were mainly enriched in multicellular organism development, cell junction, ion binding and cardiac conduction. The PPI network contained 4886 nodes and 10342 edges. HSP90AA1, FN1, KIT, YAP1, LSM2, SKP1, EIF5A2, TAF9, DDX39B and CDK7 were identified as the top hub genes. The regulatory network analysis revealed that microRNA (miRNA) hsa-mir-545-3p and hsa-miR-548f-5p, and transcription factor (TF) PLAG1 and MEF2A might be involved in the development of AD. These findings provide new insights into the pathogenesis of AD. The hub genes, miRNAs and TFs have the potential to be used as diagnostic and therapeutic markers.

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Therapeutic Perspectives on ROCK Inhibition for Cerebral Cavernous Malformations

Montagnoli

Oliveira

Fraga

2023

Kinases and Phosphatases

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Cerebral cavernous malformations (CCM) are developmental venous dysplasias which present as abnormally dilated blood vessels occurring mainly in the brain. Alterations in vascular biology originate from somatic mutations in genes regulating angiogenesis and endothelial-to-mesenchymal transition. Vascular lesions may occur at any time and develop silently, remaining asymptomatic for years. However, symptomatic disease is often debilitating, and patients are prone to develop drug-resistant epilepsy and hemorrhages. There is no cure, and surgical treatment is recommended only for superficial lesions on cortical areas. The study of lesion biology led to the identification of different pathways related to disease onset and progression, of which RhoA/Rho-associated protein kinase (ROCK) shows activation in different subsets of patients. This work will explore the current knowledge about the involvement of ROCK in the many aspects of CCM disease, including isoform-specific actions, and delineate the recent development of ROCK inhibitors for CNS-targeted diseases.

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FOXO4 alleviates hippocampal neuronal damage in epileptic mice via the miR‐138‐5p/ROCK2 axis

Cited by 3 publications

References 59 publications

What Is the Role of the Rho-ROCK Pathway in Neurologic Disorders?

What Is the Role of the Rho-ROCK Pathway in Neurologic Disorders?

Identification of candidate biomarkers and signaling pathways associated with Alzheimer’s disease using bioinformatics analysis of next generation sequencing data

Therapeutic Perspectives on ROCK Inhibition for Cerebral Cavernous Malformations

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