“Epigenetics: Impacts on Disease Susceptibility and Pharmacotherapy” (Abubakar & Haque, 2016) in epilepsy

        Scientists have learned from epigenetics that the hereditary material that compromises all living beings, can be modified by simple and complex mechanisms, that can change completely the way it is expressed. Based on this, “genes that are linked to other diseases apart from cancer can be identified, silenced or activated using drugs or diets in order to treat the disease aetiology (or causes).” (2016)

        Since epigenetics is “involved in the control of the central nervous system and memory regulation” (2016), it has a tremendous impact on neurological disorders, such as epilepsy. This impact is made through regulation of ”genes responsible for signal transduction, inflammation, cell metabolism, ion transport, synaptic transmission, and stress” (2016). In the case of epilepsy, DNA methylation is increased in promoter regions found in temporal lobe epilepsy (TLE). This kind of epilepsy is the most common form with focal seizures. This may result in loss or trouble with memory, due to the function of the temporal lobe related to the creation of memories. The left temporal lobe is important for verbal memories, such as learning names or remembering facts for a test. Epilepsy in the left temporal lobe can cause problems remembering names and finishing sentences. The right temporal lobe is important for visual memories, such as remembering the face of another person or remembering how to get to a particular place (Epilepsy Society, 2015). Additional to hyper methylation in the promoter sequence of the temporal lobe, it has also been found in the Reelin DNA promoter. Reelin (RELN) is a large protein produced in the brain that triggers nerve cells through a signaling pathway in order to migrate them to their proper locations (Genetic Home References). “Reelin may also regulate synaptic plasticity, which is the ability of connections between neurons (synapses) to change and adapt over time in response to experience” (Genetic Home References). By over methylation of the gene that codes for the reelin protein, the proper connections between neurons cannot happen in the brain and therefore, communication is lost. “Once Reelin is silenced epigenetically, granule cell dispersion will be emerged causing epilepsy.” (Abubakar & Haque, 2016)

        Whenever someone’s been diagnosed with a health or neurological condition, the first question that arises is “can it be treated or cured?” Drugs used for treatment involving epigenetics, do not halt these epigenetic processes, but instead, correct the ketogenesis (Abubakar & Haque, 2016). There are various drugs for epigenetic pharmacotherapy, such as Vidaza, Zolinza and Vorinostat. They are divided by two classes: DNA methyltransferase inhibitors (Vidanza) and histone deacetylase inhibitors (Zolinza/Vorinostat) (Abubakar & Haque, 2016). As discussed previously on another post, a ketogenic diet with low fat, low carbohydrate, and high content, has been proven to decrease gene methylation. Similarly, these drugs also inhibit gene methylation, but on the other hand, they also promote acetylation. Another drug that works in the same way is imipramine. “DNAdemethylase removes the methyl group in the genome, and the methyl groups on the histone moiety are removed by histone demethylase. Therefore, induction of these enzymes through diet or pharmaco­therapy is likely to improve gene expression.” (Abubakar & Haque, 2016)

References:

(2015, August). How epilepsy can affect memory. Retrieved from https://www.epilepsysociety.org.uk/how-epilepsy-can-affect-memory

(2016, December). RELN gene. Retrieved from https://ghr.nlm.nih.gov/gene/RELN

Abubakar, A. & Haque, M. (2016) Epigenetics: Impact on Disease Susceptibility and Pharmacotherapy. Indian Journal of Phamaceutical Education and Research, 50(310-321).