A GABBR2 gene variant modifies pathophysiology in Huntington’s disease

Philpott, April L.; Fitzgerald, Paul B.; Bailey, Neil W.; Churchyard, Andrew; Georgiou‐Karistianis, Nellie; Cummins, Tarrant

doi:10.1016/j.neulet.2016.03.038

Cited by 8 publications

(6 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with functional enrichment results, CACNA1C , one of the hubs of CC M6 presented in both SFARI and WGS set, in which genetic variation have been associated with ASD, Major Depressive Disorder, Schizophrenia as well as some undiagnosable psychiatric illness (34). Other hub genes ( GABBR2 , GRM7 , MEF2C , SCN2A , KMT2C , and DAGLA ) dysfunction have been reported to contribute to ASD and other psychiatric disorders such as Attention-Deficit Hyperactivity Disorder (ADHD) (35), Huntington’s disease (36), and Rett-syndrome (37). These observations supported the existence of shared dysfunction convergence but might distinct mechanism under CC and PFC in ASD.…”

Section: Resultsmentioning

confidence: 99%

Integrated Analysis of Brain Transcriptome Reveals Convergent Molecular Pathways in Autism Spectrum Disorder

Zhang

Wang

et al. 2019

Front. Psychiatry

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders with etiology that remains elusive. Although there is a mounting body of investigation in different brain regions related to ASD, our knowledge about the common and distinct perturb condition between them is at the threshold of accumulation. In this study, based on protein–protein interactions, post-mortem transcriptome analysis was performed with corpus callosum (CC) and prefrontal cortex (PFC) samples from ASD individuals and controls. Co-expression network analysis revealed that a total of seven (four for CC set, three for PFC set) core dysfunctional modules strongly enriched for known ASD-risk genes. Three quarters of them in CC set (M4, M6, M29) significantly enriched for genes annotated by genetically associated variants in our previous whole genome sequencing data. We further determined transcriptional and post-transcriptional regulation subnetwork for each ASD-correlated module, including 47 pivot transcription factors, 130 pivot miRNAs, and 7 pivot lncRNAs. Moreover, there were significantly more interactions between CC-M4, -M6, and PFC-M2, mainly involved in synaptic functions and neuronal development. Our integrated multifactor analysis of ASD brain transcriptome profile illustrated underlying common and distinct molecular mechanisms and the module crosstalk between CC and PFC, helping to shed light on the molecular neuropathological underlying ASD.

show abstract

Section: Resultsmentioning

confidence: 99%

Integrated Analysis of Brain Transcriptome Reveals Convergent Molecular Pathways in Autism Spectrum Disorder

Zhang

Wang

et al. 2019

Front. Psychiatry

View full text Add to dashboard Cite

show abstract

“…Mechanically, GABBR2 downregulation inhibited the glycolysis capacity of HUVECs by downregulating the expression of glycolysis-associated enzymes. Gamma-aminobutyric acid type B receptor subunit 2 was reported to implicate in a number of neuronal disorders, including cognitive impairments, nociception, anxiety, and depression (19)(20)(21). In the neuronal pathophysiology of many CNS diseases and disorders, GABBR2 regulates intracellular signaling by G protein-coupled receptors to activate adenylyl cyclase.…”

Section: Discussionmentioning

confidence: 99%

Endothelial GABBR2 Regulates Post-ischemic Angiogenesis by Inhibiting the Glycolysis Pathway

Zhang

Zhou

Yuan

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Purpose: Angiogenesis post-ischemia plays an essential role in preventing ischemic damage to tissue by improving the blood recovery. Determining the regulatory mechanism of ischemic angiogenesis, therefore, could provide effective therapeutics for ischemic injury.Materials and Methods: The RNA sequencing (RNA-seq) database was used to predict the association of gamma-aminobutyric acid type B receptor subunit 2 (GABBR2) with endothelial-specific expression. The role of GABBR2 in angiogenesis was verified in vitro by downregulating GABBR2 in human umbilical vein endothelial cells (HUVECs) with lentiviral vectors. Besides, the in vivo effect of GABBR2 on the blood recovery of an ischemic hindlimb was demonstrated by establishing a hindlimb ischemia model in normal and GABBR2 adenoviral vector-infected mice. Then, the mobilization of endothelial progenitor cells (EPCs) in peripheral blood post-ischemia was determined by flow cytometry. Finally, the XF analyzer and Western blot were used to determine the effect of GABBR2 on endothelial metabolism.Results: The RNA-seq results indicated a strong association between GABBR2 and endothelial revascularization, and the upregulation of GABBR2 was detected in both hypoxia-treated HUVECs and ischemic mouse hindlimb. Hypoxia treatment for 6 h increased the proliferation, migration, and tube formation of HUVECs, which were inhibited by GABBR2 knockdown. Additionally, GABBR2 downregulation significantly decreased the blood flow recovery of mouse ischemic hindlimb. The expressions of the EPC markers CD34+ and CD133+ significantly decreased in the peripheral blood in hindlimb post-ischemia. Mechanically, glycolysis-dominated metabolism of HUVECs was compromised by GABBR2 knockdown. Evidences of the decreased expressions of HKII, PFKFB3, and PKM1 also supported the compromised glycolysis induced by GABBR2 downregulation.Conclusion: Our study demonstrated that GABBR2 regulated angiogenesis post-ischemia by inhibiting the glycolysis pathway.

show abstract

“…Previous studies have revealed the key role of CACNG2 in mental and neuropathic disorders, including bipolar disorder, schizophrenia (40) and chronic pain (39). GABBR2 is a protein involved in neurological disorders, such as epilepsy (41) and Huntington's disease (42). However, the roles of CACNG2 and GABBR2 in ES are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Identifying prognosis and metastasis‑associated genes associated with Ewing sarcoma by weighted gene co‑expression network analysis

Wang

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

Ewing sarcoma (ES) is a highly malignant pediatric tumor with a low survival rate and a high rate of metastasis. However, there have been limited reports on the exploration of new biomarkers of ES. Therefore, the aim of the present study was to identify the potential hub genes associated with overall vital survival (OVS) and metastasis in ES. Traditional methods for identifying differentially expressed genes lack the in-depth information of mechanistic studies. In this study, a weighted co-expression network for ES was constructed through weighted gene co-expression network analysis to identify co-expression modules associated with clinical phenotypes. The hub genes in the metastasis- and OVS-related co-expression modules were extracted, and the association between the hub genes and patient OVS was verified in another independent Gene Expression Omnibus dataset. Functional annotations and protein-protein interaction analysis of co-expression modules were also used to understand the potential regulatory mechanisms. The results of the functional enrichment analysis revealed that the OVS-associated module was mainly enriched in the cell cycle and immune response, and the metastasis-associated module was enriched in metabolism. A total of four genes (proteasome subunit α4, L1 cell adhesion molecule, serine/threonine kinase receptor-associated protein and cytotoxic T-lymphocyte-associated protein 4) in the OVS-related module and two genes (calcium voltage-gated channel auxiliary subunit γ2 and γ-aminobutyric acid type B receptor subunit 2) in the metastasis-related module were selected as hub genes. Further research on the hub genes identified in the present study may contribute to the understanding of the mechanism of ES metastasis and progression.

show abstract

A GABBR2 gene variant modifies pathophysiology in Huntington’s disease

Cited by 8 publications

References 45 publications

Integrated Analysis of Brain Transcriptome Reveals Convergent Molecular Pathways in Autism Spectrum Disorder

Integrated Analysis of Brain Transcriptome Reveals Convergent Molecular Pathways in Autism Spectrum Disorder

Endothelial GABBR2 Regulates Post-ischemic Angiogenesis by Inhibiting the Glycolysis Pathway

Identifying prognosis and metastasis‑associated genes associated with Ewing sarcoma by weighted gene co‑expression network analysis

Contact Info

Product

Resources

About