Protocadherin 19 Clustering Epilepsy and Neurosteroids: Opportunities for Intervention
Abstract
:1. Introduction
2. Role of Steroids in CE
2.1. Clinical Evidence
2.2. Gene-Expression Evidence
2.2.1. Aldo-Keto Reductase Family 1 Member C3 (AKR1C3)
2.2.2. Oxytocin Receptor (OXTR)
2.2.3. Apolipoprotein D (APOD)
2.2.4. PCDH19 as a Coregulator of NHR-Mediated Gene Regulation
2.3. Cellular Evidence
3. Opportunities for Intervention
4. CE Mouse Model
5. Conclusions and Challenges
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACTH | Adrenocorticotropic hormone |
ADHD | Hyperactive and/or attention-deficit disorder |
AED | Antiepileptic drug |
AKR1C2-4 | Aldo-keto reductase 1C2-4 |
APOD | Apolipoprotein D |
AR | Androgen receptor |
ASD | Autism spectrum disorder |
CDD | CDKL5 deficiency disorder |
CE | Clustering epilepsy |
Cg | Chorionic gonadotropin |
CRISPR | Clustered regularly interspaced short palindromic repeats |
DHT | Dihydrotestosterone |
DSD | Disordered sexual development |
ECoG | Electrocorticogram |
ERα | Estrogen receptor α |
GABAAR | γ-aminobutyric acid type A receptors |
GRIA1 | Glutamate receptor 1 |
iPSCs | Induced pluripotent stem cells |
KO | Knock-out |
MT | Mutant |
NHR | Nuclear hormone receptor |
NONO | Non-POU-domain-containing octamer-binding protein |
OXT | Oxytocin |
OXTR | Oxytocin receptor |
PCDH19 | Protocadherin 19 |
PGR | Progesterone receptor |
PS | Pregnenolone sulfate |
PTZ | Pentylenetetrazol |
SWD | Spike-wave discharge |
TBR2 | T-box brain protein 2 |
WT | Wildtype |
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Hormone-Based Treatment | No. of Patients | Age | Seizure Reduction (≥50%) | Reference |
---|---|---|---|---|
Corticosteroids | 5 | 10 months–11.6 years | 5/5 after the first or second treatment. Clustering recurred within 3 weeks with the onset of fever for 3/5. | [64] |
Corticosteroids | 1 | 8 years | 1/1. | [64] |
Ganaxolone Phase II | 11 | 4–15 years | 4/11. | [66] |
Steroids | 3 | Unknown | 1/3 after 3 months of treatment. 0/3 after 12 months of treatment. | [59] |
Vitamin B6 | 2 | 7–8 years | 0/2 | [63] |
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de Nys, R.; Kumar, R.; Gecz, J. Protocadherin 19 Clustering Epilepsy and Neurosteroids: Opportunities for Intervention. Int. J. Mol. Sci. 2021, 22, 9769. https://doi.org/10.3390/ijms22189769
de Nys R, Kumar R, Gecz J. Protocadherin 19 Clustering Epilepsy and Neurosteroids: Opportunities for Intervention. International Journal of Molecular Sciences. 2021; 22(18):9769. https://doi.org/10.3390/ijms22189769
Chicago/Turabian Stylede Nys, Rebekah, Raman Kumar, and Jozef Gecz. 2021. "Protocadherin 19 Clustering Epilepsy and Neurosteroids: Opportunities for Intervention" International Journal of Molecular Sciences 22, no. 18: 9769. https://doi.org/10.3390/ijms22189769