Autoantobodies activate small GTPase RhoA to modulate neurite outgrowth

Sheikh, Kazim A.

doi:10.4161/sgtp.2.4.17115

Cited by 8 publications

(2 citation statements)

References 51 publications

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“…RhoA binding with the C-terminal domain of ROCK, forming the Rho A/ROCK pathway, and controls a wide variety of cellular processes dependent on the re-arrangement of the actin cytoskeleton and changes of cell contractility. Yet, ROCK does not directly act on cytoskeletal molecules and ERM (radixin/ezrin/moesin) proteins are emerged as the candidates that likely linking the activation of ROCK and the cytoskeleton reorganization [ 27 , 28 ]. Moesin is one of the most important and it has been reported that Rho A/ROCK is a typical upstream pathway for the phosphorylation of moesin [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer

et al. 2016

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BackgroundThe 5-year survival rate of patients with hepatocellular cancer (HCC) was very low because of invasion and metastasis in the early stage. Biomarkers might help predict early occurrence of invasion and metastasis. Accumulating evidence has shown that deleted in liver cancer-1 (DLC1) may be considered as a metastasis suppressor gene in numerous solid and hematological cancers. However, its prognostic role and mechanisms that regulate and coordinate these activities remain poorly understood.MethodsWith the method of immunohistochemistry, the expression of DLC-1 as well as Rho A, ROCK2, moesin had been characterized in 80 HCC tissues and adjacent noncancerous tissues. The correlation between their expression and their relationships with clinicopathological characteristics of HCC were also investigated. In addition, the prognostic value of DLC1 expression within the tumor tissues was assessed by Cox regression and Kaplan-Meier analysis.Results DLC1 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues, and DLC-1 expression was found to be negatively correlated with tumor differentiation, TNM stage and lymph node metastasis. Furthermore, DLC-1 expression was found to inversely correlate with Rho A, ROCK2 and moesin which were all highly expressed in HCC tissues. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in HCC patients with higher DLC1 expression, compared to those with lower expression of DLC1. Multivariate Cox proportional hazard analyses revealed that DLC1 was an independent factor affecting the overall survival probability.ConclusionDLC1 could be served as a tumor suppressor gene in the progression especially in the invasion and metastasis of HCC. DLC1 perhaps played its role by regulating the expression of Rho A, ROCK2 and moesin. Evaluation of the expression of DLC-1 might be a good prognostic marker for patients with HCC.

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Section: Discussionmentioning

confidence: 99%

DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer

et al. 2016

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“…In severe cases, axon degeneration may be seen as a bystander associated with the demyelination phenomenon [10]. The axonal pattern of GBS, where primary axonal degeneration is observed with a lack of or lesser demyelination, has a low incidence in Europe and Northern America; however, it is more frequent in China, Japan and probably other developing countries, especially in regions where Campylobacter infection is prevalent [11,12]. First evidence was offered by Feasby et al [13] indicating some cases of GBS which may have occurred due to primary sensory and motor axonal degeneration without previous demyelination or the target antigen located on the axon [13].…”

Section: Introductionmentioning

confidence: 99%

Evaluating the Status of Antiganglioside Antibodies in Children with Guillain-Barré Syndrome

Hashemilar

Barzegar²,

Nikanfar³

et al. 2013

Neuroimmunomodulation

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Objective: Antiganglioside antibodies have been reported to play a role in the pathophysiology of Guillain-Barré syndrome (GBS). Methods: This case-control study was designed to evaluate the status of antiganglioside antibodies in children with GBS. The study included 50 patients suffering from GBS as the case group and 30 children as the control group. Clinical information such as demographic data and recent digestive or respiratory infection (within the last month) was collected for all patients, and paraclinical studies including cerebrospinal fluid examination and electrophysiology were conducted by a subspecialized physician. Anti-GM1, anti-GQ1 and anti-GD1a antibodies were measured with ELISA and the EUROLINE method. Results: The mean age of patients in the case and control groups was 5.3 ± 3.8 and 5.4 ± 3.4 years, respectively. With the EUROLINE method, the results obtained for anti-GM1 were significant (p = 0.007); however, the p values for anti-GQ1a and anti-GQ1b were not significant (0.051 vs. 0.94), while with ELISA, comparing all three antibodies in both the case and control groups showed statistically significant results, with a p < 0.05. Conclusion: EUROLINE is a new method used to evaluate antibodies in immune system diseases, but it is not useful for all antibodies specific to GBS, as the analysis was significant with a p value of 0.007 for anti-GM2.

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Dissecting the Role of Anti-ganglioside Antibodies in Guillain-Barré Syndrome: an Animal Model Approach

et al. 2015

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Guillain-Barré syndrome (GBS) is an autoimmune polyneuropathy disease affecting the peripheral nervous system (PNS). Most of the GBS patients experienced neurological symptoms such as paresthesia, weakness, pain, and areflexia. There are also combinations of non-neurological symptoms which include upper respiratory tract infection and diarrhea. One of the major causes of GBS is due largely to the autoantibodies against gangliosides located on the peripheral nerves. Gangliosides are sialic acid-bearing glycosphingolipids consisting of a ceramide lipid anchor with one or more sialic acids attached to a neutral sugar backbone. Molecular mimicry between the outer components of oligosaccharide of gangliosides on nerve membrane and lipo-oligosaccharide of microbes is thought to trigger the autoimmunity. Intra-peritoneal implantation of monoclonal ganglioside antibodies secreting hybridoma into animals induced peripheral neuropathy. Recent studies demonstrated that injection of synthesized anti-ganglioside antibodies raised by hybridoma cells into mice initiates immune response against peripheral nerves, and eventually failure in peripheral nerve regeneration. Accumulating evidences indicate that the conjugation of anti-ganglioside monoclonal antibodies to activating FcγRIII present on the circulating macrophages inhibits axonal regeneration. The activation of RhoA signaling pathways is also involved in neurite outgrowth inhibition. However, the link between these two molecular events remains unresolved and requires further investigation. Development of anti-ganglioside antagonists can serve as targeted therapy for the treatment of GBS and will open a new approach of drug development with maximum efficacy and specificity.

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Autoantobodies activate small GTPase RhoA to modulate neurite outgrowth

Cited by 8 publications

References 51 publications

DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer

DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer

Evaluating the Status of Antiganglioside Antibodies in Children with Guillain-Barré Syndrome

Dissecting the Role of Anti-ganglioside Antibodies in Guillain-Barré Syndrome: an Animal Model Approach

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