GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case–control study

Ercegovac, Marko; Jović, N.; Sokić, Dragoslav; Savić-Radojević, Ana; Ćorić, Vesna; Radić, Tanja; Nikolić, Dimitrije; Kecmanović, M; Matić, Marija; Simić, Tatjana; Plješa-Ercegovac, Marija

doi:10.1016/j.seizure.2015.08.010

Cited by 37 publications

(19 citation statements)

References 39 publications

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“…It is also interesting to outline that almost half of the proteins that are differentially expressed in EPM1‐derived organoids and enriched in radial glial cells are involved in different types of human epilepsies. For instance, Collagen COL11A1 mutated in the Stickler syndrome, caused by mutations in COL2A1 or COL11A1, is associated with epileptic phenotypes (Savasta et al , ; Zhou et al , ); IFITM3 (interferon‐induced transmembrane protein 3) has been identified among genes that are target of epilepsy‐associated miRNA in animal models and human tissues (Cava et al , ); heterozygous mutation in GLUD1 gene has been reported in patients affected by hyperinsulinism, commonly associated with epileptic seizures (Aka et al , ); RRAS (Guo et al , ) and MGST1 (Shang et al , ; Ercegovac et al , ) are associated with epilepsy risk.…”

Section: Discussionmentioning

confidence: 99%

Cystatin B is essential for proliferation and interneuron migration in individuals with EPM 1 epilepsy

et al. 2020

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Progressive myoclonus epilepsy (PME) of Unverricht-Lundborg type (EPM1) is an autosomal recessive neurodegenerative disorder with the highest incidence of PME worldwide. Mutations in the gene encoding cystatin B (CSTB) are the primary genetic cause of EPM1. Here, we investigate the role of CSTB during neurogenesis in vivo in the developing mouse brain and in vitro in human cerebral organoids (hCOs) derived from EPM1 patients. We find that CSTB (but not one of its pathological variants) is secreted into the mouse cerebral spinal fluid and the conditioned media from hCOs. In embryonic mouse brain, we find that functional CSTB influences progenitors' proliferation and modulates neuronal distribution by attracting interneurons to the site of secretion via cell-non-autonomous mechanisms. Similarly, in patient-derived hCOs, low levels of functional CSTB result in an alteration of progenitor's proliferation, premature differentiation, and changes in interneurons migration. Secretion and extracellular matrix organization are the biological processes particularly affected as suggested by a proteomic analysis in patients' hCOs. Overall, our study sheds new light on the cellular mechanisms underlying the development of EPM1.

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Section: Discussionmentioning

confidence: 99%

Cystatin B is essential for proliferation and interneuron migration in individuals with EPM 1 epilepsy

et al. 2020

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“…Epilepsy is a disease of the brain, the distinctive characteristic of which is a predisposition to generate unprovoked seizures 59 . The association between polymorphisms of GST genes and the risk of epilepsy has been investigated in several studies 60 – 62 . In patients with progressive myoclonus epilepsy, a GSTT1 -null genotype has been associated with increased risk of developing the disease where it might contribute to enhanced susceptibility to oxidative stress 60 .…”

Section: Gsts Gene Polymorphisms and Correlation To Diseasesmentioning

confidence: 99%

“…The association between polymorphisms of GST genes and the risk of epilepsy has been investigated in several studies 60 – 62 . In patients with progressive myoclonus epilepsy, a GSTT1 -null genotype has been associated with increased risk of developing the disease where it might contribute to enhanced susceptibility to oxidative stress 60 . Different results were obtained in other group of patients 61 .…”

Section: Gsts Gene Polymorphisms and Correlation To Diseasesmentioning

confidence: 99%

Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases

et al. 2018

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Glutathione transferase classical GSH conjugation activity plays a critical role in cellular detoxification against xenobiotics and noxious compounds as well as against oxidative stress. However, this feature is also exploited by cancer cells to acquire drug resistance and improve their survival. As a result, various members of the family were found overexpressed in a number of different cancers. Moreover several GST polymorphisms, ranging from null phenotypes to point mutations, were detected in members of the family and found to correlate with the onset of neuro-degenerative diseases. In the last decades, a great deal of research aimed at clarifying the role played by GSTs in drug resistance, at developing inhibitors to counteract this activity but also at exploiting GSTs for prodrugs specific activation in cancer cells. Here we summarize some of the most important achievements reached in this lively area of research.

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“…Finally, the result demonstrated influence of Ala16Val MnSOD polymorphism, mainly of VV genotype in epilepsy patients. Accordingly, studies have shown that the polymorphism of some genes may be related to the efficacy, tolerability, and action of antiepileptic drugs [48,49].…”

Section: Resultsmentioning

confidence: 99%

Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL‐1β and IL‐6 Pathways

Kegler

Caprara

Pascotini

et al. 2020

BioMed Research International

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The MnSOD Ala16Val single nucleotide polymorphism (SNP) has been associated with different diseases. However, there are scarcely studies relating this SNP in epilepsy, a neurologic disease that involves some interacting pathways, such as apoptotic and inflammatory factors. In this sense, we decided to investigate the relationship of MnSOD Ala16Val SNP with apoptotic markers in epilepsy and its relation with inflammatory pathway and seizure type. Ninety subjects were evaluated (47 epilepsies; 43 controls) by questionnaires and laboratorial exams. We observed a higher percentage of VV genotype in the epilepsy group when compared to the control group. IL-1β, IL-6, caspase-1, and caspase-3 levels were increased in the epilepsy group (VV genotype). Furthermore, an important correlation between IL-1β vs. caspase-1 and IL-6 vs. caspase-3 was observed in the epilepsy group (VV genotype). The epilepsy group which presented generalized seizures also demonstrated a positive correlation between IL-1β vs. CASP1 and IL-6 vs. CASP3. Thus, it is a plausible propose that epilepsy patients with VV genotype and generalized seizures present a worse inflammatory and apoptotic status. Our findings suggest that the knowledge of MnSOD Ala16Val polymorphism existence is important to evaluate molecular mechanisms associated to seizure and improve the treatment of these patients.

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GSTA1, GSTM1, GSTP1 and GSTT1 polymorphisms in progressive myoclonus epilepsy: A Serbian case–control study

Abstract: GSTT1-null genotype might be associated with the increased risk and enhanced susceptibility to oxidative stress in PME patients.

Cited by 37 publications

References 39 publications

Cystatin B is essential for proliferation and interneuron migration in individuals with EPM 1 epilepsy

Cystatin B is essential for proliferation and interneuron migration in individuals with EPM 1 epilepsy

Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases

Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL‐1β and IL‐6 Pathways

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