Immunotherapy by targeting of VGKC complex for seizure control and prevention of cognitive impairment in a mouse model of epilepsy

Zhang, Fan; Feng, Xiaojuan; Fan, Zhipeng; Zhu, Xiaojun; Yin, Shanshan

doi:10.3892/mmr.2018.9004

Cited by 3 publications

(3 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, these crucial genes were not involved in KEGG pathway-related regulation. Previous research has shown that three of the four key potassium channel genes (KCNA1, KCNA2, KCNJ11, and KCNS1) play vital roles in seizures and epilepsy (8)(9)(10). Four key potassium channel genes Lines are used to mark the position of members from the gene set in the gene sorting list, and the black line represents that the genes from the sorting gene table exist in the functional annotation gene set of the current analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Potassium channels in cell membranes play a critical role in regulating neuronal excitability by controlling the transport of potassium ions across cells (4)(5)(6). Several potassium channels are associated with TLE, primarily based on animal experiments (7)(8)(9)(10). Research on the association between potassium levels and epilepsy may provide novel insights into the mechanisms and treatments of epilepsy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

et al. 2023

View full text Add to dashboard Cite

One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member (KCNA) 1, KCNA2, potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11), and KCNS1. A protein–protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target KCNA1, KCNA2, and KCNS1. Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for KCNJ11. Compared to normal mice, the expression of KCNA1, KCNA2, KCNJ11, and KCNS1 was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The mice treated with VGKC antibodies had also inhibited motor seizures and hippocampal damage, compared with control mice. It is suggested that VGKC may even be a potential target for the treatment of epilepsy (171).…”

Section: Antibodies: Glyr Antibodiesmentioning

confidence: 99%

Autoimmune Epilepsy - Novel Multidisciplinary Analysis, Discoveries and Insights

Levite

Goldberg

2022

Front. Immunol.

View full text Add to dashboard Cite

Epilepsy affects ~50 million people. In ~30% of patients the etiology is unknown, and ~30% are unresponsive to anti-epileptic drugs. Intractable epilepsy often leads to multiple seizures daily or weekly, lasting for years, and accompanied by cognitive, behavioral, and psychiatric problems. This multidisciplinary scientific (not clinical) ‘Perspective’ article discusses Autoimmune Epilepsy from immunological, neurological and basic-science angles. The article includes summaries and novel discoveries, ideas, insights and recommendations. We summarize the characteristic features of the respective antigens, and the pathological activity in vitro and in animal models of autoimmune antibodies to: Glutamate/AMPA-GluR3, Glutamate/NMDA-NR1, Glutamate/NMDA-NR2, GAD-65, GABA-R, GLY-R, VGKC, LGI1, CASPR2, and β2 GP1, found in subpopulations of epilepsy patients. Glutamate receptor antibodies: AMPA-GluR3B peptide antibodies, seem so far as the most exclusive and pathogenic autoimmune antibodies in Autoimmune Epilepsy. They kill neural cells by three mechanisms: excitotoxicity, Reactive-Oxygen-Species, and complement-fixation, and induce and/or facilitate brain damage, seizures, and behavioral impairments. In this article we raise and discuss many more topics and new insights related to Autoimmune Epilepsy. 1. Few autoimmune antibodies tilt the balance between excitatory Glutamate and inhibitory GABA, thereby promoting neuropathology and epilepsy; 2. Many autoantigens are synaptic, and have extracellular domains. These features increase the likelihood of autoimmunity against them, and the ease with which autoimmune antibodies can reach and harm these self-proteins. 3. Several autoantigens have ‘frenetic character’- undergoing dynamic changes that can increase their antigenicity; 4. The mRNAs of the autoantigens are widely expressed in multiple organs outside the brain. If translated by default to proteins, broad spectrum detrimental autoimmunity is expected; 5. The autoimmunity can precede seizures, cause them, and be detrimental whether primary or epiphenomenon; 6. Some autoimmune antibodies induce, and associate with, cognitive, behavioral and psychiatric impairments; 7. There are evidences for epitope spreading in Autoimmune Epilepsy; 8. T cells have different ‘faces’ in the brain, and in Autoimmune Epilepsy: Normal T cells are needed for the healthy brain. Normal T cells are damaged by autoimmune antibodies to Glutamate/AMPA GluR3, which they express, and maybe by additional autoantibodies to: Dopamine-R, GABA-R, Ach-R, Serotonin-R, and Adrenergic-R, present in various neurological diseases (summarized herein), since T cells express all these Neurotransmitter receptors. However, autoimmune and/or cytotoxic T cells damage the brain; 9. The HLA molecules are important for normal brain function. The HLA haplotype can confer susceptibility or protection from Autoimmune Epilepsy; 10. There are several therapeutic strategies for Autoimmune Epilepsy.

show abstract

Scoping review of disease-modifying effect of drugs in experimental epilepsy

et al. 2023

View full text Add to dashboard Cite

ObjectiveEpilepsy affects ~50 million people worldwide causing significant medical, financial, and sociologic concerns for affected patients and their families. To date, treatment of epilepsy is primarily symptomatic management because few effective preventative or disease-modifying interventions exist. However, recent research has identified neurobiological mechanisms of epileptogenesis, providing new pharmacologic targets to investigate. The current scientific evidence remains scattered across multiple studies using different model and experimental designs. The review compiles different models of anti-epileptogenic investigation and highlights specific compounds with potential epileptogenesis-modifying experimental drugs. It provides a platform for standardization of future epilepsy research to allow a more robust compound analysis of compounds with potential for epilepsy prevention.MethodsPubMed, Ovid MEDLINE, and Web of Science were searched from 2007 to 2021. Studies with murine models of epileptogenesis and explicitly detailed experimental procedures were included in the scoping review. In total, 51 articles were selected from 14,983 and then grouped by five core variables: (1) seizure frequency, (2) seizure severity, (3) spontaneous recurrent seizures (SRS), (4) seizure duration, and (5) mossy fiber sprouting (MFS). The variables were differentiated based on experimental models including methods of seizure induction, treatment schedule and timeline of data collection. Data was categorized by the five core variables and analyzed by converting original treatment values to units of percent of its respective control.ResultsDiscrepancies in current epileptogenesis models significantly complicate inter-study comparison of potential anti-epileptogenic interventions. With our analysis, many compounds showed a potential to reduce epileptogenic characteristics defined by the five core variables. WIN55,212-2, aspirin, rapamycin, 1400W, and LEV + BQ788 were identified compounds with the potential of effective anti-epileptic properties.SignificanceOur review highlights the need for consistent methodology in epilepsy research and provides a novel approach for future research. Inconsistent experimental designs hinder study comparison, slowing the progression of treatments for epilepsy. If the research community can optimize and standardize parameters such as methods of seizure induction, administration schedule, sampling time, and aniMal models, more robust meta-analysis and collaborative research would follow. Additionally, some compounds such as rapamycin, WIN 55,212-2, aspirin, 1400W, and LEV + BQ788 showed anti-epileptogenic modulation across multiple variables. We believe they warrant further study both individually and synergistically.

show abstract

Immunotherapy by targeting of VGKC complex for seizure control and prevention of cognitive impairment in a mouse model of epilepsy

Cited by 3 publications

References 49 publications

Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

Autoimmune Epilepsy - Novel Multidisciplinary Analysis, Discoveries and Insights

Scoping review of disease-modifying effect of drugs in experimental epilepsy

Contact Info

Product

Resources

About