The role of Rho/ROCK in epileptic seizure-related neuronal damage

Wang, Zhihan; Ren, Dianxu; Zheng, Ping

doi:10.1007/s11011-022-00909-6

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…Y-27632 is the most common ROCK inhibitor and is frequently utilized in cardiovascular disease studies 24 , 25 . ROCK plays important roles in various biological processes, such as cell proliferation, metastasis, and apoptosis, as well as cell cycle regulation 26 . Currently, the EAM mouse model is the most commonly used experimental model for determining the immune mechanism of myocarditis pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Rho kinase inhibitor Y-27632 downregulates IL-1β expression in mice with experimental autoimmune myocarditis

Li,

Gao,

Han

et al. 2024

Sci Rep

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Autoimmune myocarditis is the limited or diffuse inflammation of the myocardium due to dysfunctional cellular and humoral immunity mechanisms. We constructed mouse models of experimental autoimmune myocarditis (EAM) using peptide MyHC-α614-629. On the day after secondary immunization, the mice were intraperitoneally injected with Rho kinase (ROCK) inhibitor Y-27632. On day 21, the cardiac tissues were harvested and weighed. The hearts of EAM mice were significantly enlarged and whitened. Furthermore, body weight (BW) slowly increased during the treatment period, the heart weight (HW) and the ratio of HW/eventual BW were increased, and inflammatory infiltration and fibrosis were aggravated in the myocardial tissue. Y-27632 treatment improved the aforementioned phenotypic and pathological features of EAM mice. Mechanistic analysis revealed a significant increase in Notch1, Hes1, Jag2, Dil1, Toll-like receptor (Tlr) 2, and interleukin (IL)-1β expression in the myocardial tissue of EAM mice. Notably, IL-1β expression was correlated with that of Notch1 and Tlr2. Following Y-27632 treatment, the expression of key target genes of the Notch signaling pathway (Notch1, Hes1, Dil1, and Jag2) and Tlr2 were obviously decreased. Y-27632 treatment also decreased the number of monocytes in the spleen of EAM mice. Thus, ROCK inhibitor Y-27632 exerted a protective effect in EAM mice by downregulating IL-1β expression. This study aimed to provide a reference point for the future treatment of myocarditis in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Rho kinase inhibitor Y-27632 downregulates IL-1β expression in mice with experimental autoimmune myocarditis

Li,

Gao,

Han

et al. 2024

Sci Rep

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show abstract

“…Y-27632, the most common ROCK inhibitor, is frequently utilized in studies on cardiovascular disease [22,23]. ROCK plays an important role in various biological processes such as cell proliferation, metastasis, apoptosis and cycle regulation [24]. The EAM mouse model is currently the most commonly used experimental model for determining the immune mechanism of myocarditis pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

ROCK inhibitor Y-27632 down-regulates Il-1β expression in mice with experimental autoimmune myocarditis

Li,

Gao,

Han

et al. 2023

Preprint

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Autoimmune myocarditis is a limited or diffuse inflammation of the myocardium brought on by dysfunction in the normal function of cellular and humoral immunity of the body. Mouse models of experimental autoimmune myocarditis (EAM) were constructed using peptide MyHC-α614–629. After secondary immunization, the mice were given intraperitoneal injection of the Rho kinase (ROCK) inhibitor Y-27632 the next day, and the heart tissues of the EAM mice were isolated and weighed on day 21. As a result, the hearts of EAM mice were significantly enlarged and whitened; the body weight (BW) of mice in the EAM group increased slowly, and the heart weight (HW) and the ratio of HW/eventual body weight (e-BW) were raised; the inflammatory infiltration and fibrosis of the myocardial tissue were aggravated. But Y-27632 treatment improved the above-mentioned phenotypic or pathological features of EAM mice. Besides, the monocytes in the spleen of EAM mice mounted up, which showed a decline in number after Y-27632 treatment. Mechanistic analysis revealed a significant increase in the expression of Notch1, Hes1, Jag2, Dil1, Tlr2 and Il-1β in the myocardial tissue of the EAM mice. Notably, the expression of IL-1β was consistent with that of Notch1 and Tlr2. After Y-27632 treatment, the expression of key target genes (Notch1, Hes1, Dil1 and Jag2) of the NOTCH signaling pathway and Tlr2 expression were obviously decreased. The ROCK inhibitor Y-27632 exerts a protective effect in EAM mice by down-regulating Il-1β expression. This study aims to provide a reference value for the future treatment of myocarditis in clinical settings.

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“…[4][5][6][7][8]. These disorders include Alzheimer disease (AD), 13,[78][79][80] Parkinson disease (PD), 81,82 tauopathies, 83 Huntington disease (HD), [84][85][86] amyotrophic lateral sclerosis (ALS), [87][88][89] spinal muscular atrophy (SMA), 11,51,90 stroke, 91,92 spinal cord injury, 93,94 traumatic brain injury, 95 epilepsy, 96 and cerebral cavernous malformation (CCM). 97,98…”

Section: Clinical Correlationsmentioning

confidence: 99%

“…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: Other Neurologic Disordersmentioning

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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The role of Rho/ROCK in epileptic seizure-related neuronal damage

Cited by 9 publications

References 44 publications

Rho kinase inhibitor Y-27632 downregulates IL-1β expression in mice with experimental autoimmune myocarditis

Rho kinase inhibitor Y-27632 downregulates IL-1β expression in mice with experimental autoimmune myocarditis

ROCK inhibitor Y-27632 down-regulates Il-1β expression in mice with experimental autoimmune myocarditis

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

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