AI Article Synopsis
- Traumatic brain injury (TBI) leads to significant brain damage and can cause lasting cognitive issues, with effective treatments still difficult to find.
- The RhoA-ROCK signaling pathway, activated by TBI, is important as it can negatively impact dendritic spines crucial for memory and information processing.
- Blocking RhoA-ROCK signaling through methods like gene deletion or using the drug fasudil shows potential to improve motor and cognitive function after TBI, suggesting it may offer a new treatment avenue.
Article Abstract
Traumatic brain injury (TBI) causes extensive neural damage, often resulting in long-term cognitive impairments. Unfortunately, effective treatments for TBI remain elusive. The RhoA-ROCK signaling pathway is a potential therapeutic target since it is activated by TBI and can promote the retraction of dendritic spines/synapses, which are critical for information processing and memory storage. To test this hypothesis, RhoA-ROCK signaling was blocked by RhoA deletion from postnatal neurons or treatment with the ROCK inhibitor fasudil. We found that TBI impairs both motor and cognitive performance and inhibiting RhoA-ROCK signaling alleviates these deficits. Moreover, RhoA-ROCK inhibition prevents TBI-induced spine remodeling and mature spine loss. These data argue that TBI elicits pathological spine remodeling that contributes to behavioral deficits by altering synaptic connections, and RhoA-ROCK inhibition enhances functional recovery by blocking this detrimental effect. As fasudil has been safely used in humans, our results suggest that it could be repurposed to treat TBI.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587534 | PMC |
| http://dx.doi.org/10.1038/s41598-017-11113-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Loss of NUMB drives aggressive bladder cancer via a RHOA/ROCK/YAP signaling axis.
Nat Commun
December 2024
European Institute of Oncology IRCCS, Milan, Italy.
Advances in bladder cancer (BCa) treatment have been hampered by the lack of predictive biomarkers and targeted therapies. Here, we demonstrate that loss of the tumor suppressor NUMB promotes aggressive bladder tumorigenesis and worsens disease outcomes. Retrospective cohort studies show that NUMB-loss correlates with poor prognosis in post-cystectomy muscle-invasive BCa patients and increased risk of muscle invasion progression in non-muscle invasive BCa patients.
View Article and Find Full Text PDFHydroxysafflor yellow A, a natural food pigment, ameliorates atherosclerosis in ApoE mice by inhibiting the SphK1/S1P/S1PR3 pathway.
Food Sci Nutr
November 2024
Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong Key Laboratory of Metabolic Disease Prevention and Treatment of Traditional Chinese Medicine, Institute of Chinese Medicine Guangdong Pharmaceutical University Guangzhou Guangdong China.
Atherosclerosis (AS) is the pathologic basis of many cardiovascular diseases (CVDs). Hydroxysafflor yellow A (HSYA) is a valuable natural food pigment that has been reported to have significant health-promoting abilities. However, the anti-AS efficacy and mechanisms of HSYA have not yet been characterized.
View Article and Find Full Text PDFBisphenol A disrupts the neuronal F-actin cytoskeleton by activating the RhoA/ROCK/LIMK pathway in Neuro-2a cells.
Toxicology
December 2024
Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China; Key Laboratory of Environment-related Diseases and TCM Prevention and Control in Universities of Shaanxi Province, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China. Electronic address:
Bisphenol A (BPA) is an environmental endocrine disruptor that is widely present in the environment and has been reported to affect neuronal cytoskeleton and neural function. However, the exact molecular mechanisms remain unclear. In the present study, the effects of BPA on cytoskeleton rearrangement were examined, and the associated signaling pathways, which were influenced by the RhoA/ROCK/LIMK pathway in Neuro-2a cells in vitro, were identified.
View Article and Find Full Text PDFMulti-omics reveals the alleviating effect of berberine on ulcerative colitis through modulating the gut microbiome and bile acid metabolism in the gut-liver axis.
Front Pharmacol
October 2024
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
The dysfunction of gut microbiome and bile acid metabolism might cause the incidence and relapse of ulcerative colitis (UC). Thus, natural products have been considered effective for UC through the regulation of gut microbiome and bile acid. In this study, we evaluated the regulatory effect of berberine on gut microbiome and bile acid metabolism in UC.
View Article and Find Full Text PDFGalangin Regulates Astrocyte Phenotypes to Ameliorate Cerebral Ischemia-reperfusion Injury by Inhibiting the RhoA/ROCK/LIMK Pathway.
Curr Pharm Des
October 2024
Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Purpose: This study aimed to explore whether Galangin (Gal) could improve cerebral Ischemia- reperfusion (I/R) injury by regulating astrocytes, and clarify its potential molecular mechanism.
Methods: An I/R injury model of rats was established using the Middle Cerebral Artery Occlusion/Reperfusion (MCAO/R) method, followed by the administration of Gal (25, 50, 100 mg/kg) via gavage for 14 consecutive days. Besides, astrocytes were isolated from the rats to construct an Oxygen-Glucose Deprivation/Re-oxygenation (OGD/R) cell model, with treatments of Gal or the Ras homolog gene family member A (RhoA)/Rho-associated Coiled-coil containing protein Kinase (ROCK) inhibitor Y-27632.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!