更新于：2024-11-01

Rho GTP酶 x ROCK1

更新于：2024-11-01

基本信息

关联

项与 Rho GTP酶 x ROCK1 相关的药物

Praconase

靶点

ROCK1 x Rho GTP酶

作用机制

ROCK1抑制剂 [+1]

在研机构-

原研机构

BioAxone Therapeutic, Inc.

在研适应症-

非在研适应症

急性脊髓损伤 [+6]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

项与 Rho GTP酶 x ROCK1 相关的临床试验

NCT02669849 / Terminated临床2/3期

A Phase 2b/3, Double-blind, Randomized, Placebo Controlled, Multicenter Study to Assess the Efficacy and Safety of VX-210 in Subjects With Acute Traumatic Cervical Spinal Cord Injury

The purpose of this study is to determine the efficacy and safety of VX-210 in subjects with Acute Traumatic Cervical Spinal Cord Injury. Secondary objectives include the specific evaluation of the effects of VX-210 on neurological recovery and daily function after spinal cord injury.

开始日期2016-07-01

申办/合作机构

Vertex Pharmaceuticals, Inc.

NCT02053883 / Withdrawn临床2/3期

A Phase II/III, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Cethrin in Subjects With Acute Cervical Spinal Cord Injury

This is a multicenter, randomized, double-blind, placebo-controlled Phase IIb/III study designed to evaluate the efficacy and safety of Cethrin as a treatment for acute cervical spinal cord injury. During the trial, high and low doses of Cethrin will be compared with placebo.

开始日期2015-07-01

申办/合作机构

BioAxone BioSciences, Inc.

NCT00500812 / Completed临床1/2期

A Phase I/IIa Dose-Ranging Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BA-210 and the Neurological Status of Patients Following Administration of a Single Extradural Application of Cethrin During Surgery for Acute Thoracic and Cervical Spinal Cord Injury

This trial is a multi-center, open-label, dose-escalation study designed to evaluate the safety, tolerability and pharmacokinetics of Cethrin in two types of spinal cord injury patients: those with a complete cervical injury or a complete thoracic injury. Dose levels from 0.3 mg - 9 mg of Cethrin will be administered.

开始日期2005-02-01

申办/合作机构

Vertex Pharmaceuticals, Inc.

100 项与 Rho GTP酶 x ROCK1 相关的临床结果

登录后查看更多信息

100 项与 Rho GTP酶 x ROCK1 相关的转化医学

登录后查看更多信息

0 项与 Rho GTP酶 x ROCK1 相关的专利（医药）

登录后查看更多信息

项与 Rho GTP酶 x ROCK1 相关的文献（医药）

2024-05-01·Current Molecular Medicine

siRNA Mediated Downregulation of RhoA Expression Reduces Oxidative Induced Apoptosis in Retinal Ganglion Cells

Article

作者: Liu, Qian ; Liu, Changgeng ; Lei, Bo

Backgrounds:Glaucoma is the second leading cause of blindness. Apoptosis of retinal ganglion cells (RGCs) is an important mechanism of glaucomatous optic injury. Rho kinase expression is significantly increased in apoptotic RGCs. This study aimed to investigate the role of RhoA, a Rho GTPase, on the survival of RGCs and further to explore its potential therapeutic applications.Methods:RGCs were treated with siRhoA for 24 hours in vitro. Knockdown of RhoA was confirmed with quantitative RT-PCR. Oxidative stress was induced by treating the RGCs with 200 μM of H2O2 for 1 hour, and apoptosis of RGCs was quantified with TUNEL assay in situ, and with flow cytometry. The mRNA expression levels of RhoA, Nogo receptor, caspase 3 and Bcl-2 were evaluated by quantitative RT-PCR, and the protein levels of RhoA, ROCK1, ROCK2, Nogo receptor, caspase 3 and Bcl-2 were evaluated by Western blot. We found siRhoA treatment efficiently downregulated the expression of RhoA in RGCs and protected against H2O2-induced injury in RGCs in vitro. Apoptosis of RGC cells under oxidative stress was quantified in situ using TUNEL assay and confirmed with flow cytometry (FCM).Results:With the knockdown of RhoA, the expression of ROCK1, ROCK2, Nogo Receptor, Casepase-3 were decreased, while the expression of Bcl-2 was increased in both mRNA and protein level. Our data indicated that siRhoA prevented H2O2-induced apoptosis in RGC cells by modulating the RhoA/ROCK pathway.Conclusion:The results suggested that siRhoA may exert potentially effective neuroprotection for RGCs by reducing injury.

2024-03-01·Glia

Epileptic activity triggers rapid ROCK1‐dependent astrocyte morphology changes

Article

作者: Abramian, Adlin ; Kim, Young-Bum ; Breithausen, Björn ; Henneberger, Christian ; Herde, Michel K ; Behringer, Charlotte ; Steinhäuser, Christian ; Bedner, Peter ; Domingos, Cátia ; Unichenko, Petr ; Minge, Daniel ; Deshpande, Tushar ; Anders, Stefanie ; Henning, Lukas ; Boehlen, Anne ; Pitsch, Julika

AbstractLong‐term modifications of astrocyte function and morphology are well known to occur in epilepsy. They are implicated in the development and manifestation of the disease, but the relevant mechanisms and their pathophysiological role are not firmly established. For instance, it is unclear how quickly the onset of epileptic activity triggers astrocyte morphology changes and what the relevant molecular signals are. We therefore used two‐photon excitation fluorescence microscopy to monitor astrocyte morphology in parallel to the induction of epileptiform activity. We uncovered astrocyte morphology changes within 10–20 min under various experimental conditions in acute hippocampal slices. In vivo, induction of status epilepticus resulted in similarly altered astrocyte morphology within 30 min. Further analysis in vitro revealed a persistent volume reduction of peripheral astrocyte processes triggered by induction of epileptiform activity. In addition, an impaired diffusion within astrocytes and within the astrocyte network was observed, which most likely is a direct consequence of the astrocyte remodeling. These astrocyte morphology changes were prevented by inhibition of the Rho GTPase RhoA and of the Rho‐associated kinase (ROCK). Selective deletion of ROCK1 but not ROCK2 from astrocytes also prevented the morphology change after induction of epileptiform activity and reduced epileptiform activity. Together these observations reveal that epileptic activity triggers a rapid ROCK1‐dependent astrocyte morphology change, which is mechanistically linked to the strength of epileptiform activity. This suggests that astrocytic ROCK1 signaling is a maladaptive response of astrocytes to the onset of epileptic activity.

2023-04-20·Cell death & disease

Septin11 promotes hepatocellular carcinoma cell motility by activating RhoA to regulate cytoskeleton and cell adhesion.

Article

作者: Yang, Ying ; Wu, XingZhong ; Cai, QianQian ; Liu, Haojie ; Wang, Xiaoyan ; Chen, MeiHua ; Kuerban, Adilijiang ; Fu, Lisheng ; Ma, Mingzhe ; Dong, Yiwei

Septins as GTPases in the cytoskeleton, are linked to a broad spectrum of cellular functions, including cell migration and the progression of hepatocellular carcinoma (HCC). However, roles of SEPT11, the new member of septin, have been hardly understood in HCC. In the study, the clinical significance and biological function of SEPT11 in HCC was explored. SEPT11 was screened out by combining ATAC-seq with mRNA-seq. Role of SEPT11 in HCC was further investigated by using overexpression, shRNA and CRISPR/Cas9-mediated SEPT11-knockout cells or in vivo models. We found RNA-seq and ATAC-seq highlights LncRNA AY927503 (AY) induced SEPT11 transcription, resulting in Rho GTPase activation and cytoskeleton actin aggregation. The GTP-binding protein SEPT11 is thus considered, as a downstream factor of AY, highly expressed in various tumors, including HCC, and associated with poor prognosis of the patients. In vitro, SEPT11 overexpression promotes the migration and invasion of HCC cells, while SEPT11-knockout inhibits migration and invasion. In vivo, SEPT11-overexpressed HCC cells show high metastasis incidents but don't significantly affect proliferation. Meanwhile, we found SEPT11 targets RhoA, thereby regulating cytoskeleton rearrangement and abnormal cell adhesion through ROCK1/cofilin and FAK/paxillin signaling pathways, promoting invasion and migration of HCC. Further, we found SEPT11 facilitates the binding of GEF-H1 to RhoA, which enhances the activity of RhoA. Overall, our study confirmed function of SEPT11 in promoting metastasis in HCC, and preliminarily explored its related molecular mechanism. SEPT11 acts as an oncogene in HCC, also draws further interest regarding its clinical application as a potential therapeutic target.