Deciphering the development of epilepsy

Impaired transport proteins triggers epilepsy

14.02.2012

Researchers at the Institute of Cell and Neurobiology at the Berlin Charité have deciphered the development of epilepsy in the brain. Thus, the chronic disease of the central nervous system (CNS) is significantly influenced by the impaired function of certain cellular ion transporters.

As part of their investigations, the scientists were able to call on the Privatdozent Dr. med. Rudolf A. Deisz from the Institute of Cell and Neurobiology for the first time identified one of the causative molecular mechanisms in human tissue for the development of epilepsy. As part of the publication of their study results in the journal „The Journal of Physiology“ (JP), the researchers say that they have managed to decipher the specific disorders of nerve cells involved in the development of focal, refractory epilepsy. Accordingly, the reduction of specific cellular transport proteins plays an essential role.

Reduction of certain transport proteins causes epilepsy
According to the research team around Dr. med. Rudolf Deisz causes the reduction of so-called cellular ion transporters in the origin zone of the seizure epilepsy. Special forms of these transport proteins are impaired in their function and thus cause a misallocation of chloride ions on the nerve cells, explain the scientists. In this way, the correct signal transmission is disturbed by the inhibitory carrier GABA in the central nervous system. The misallocation of chloride ions is thus the basis of increased nerve cell activity, as it has a significant influence on the effectiveness of the inhibitory GABA effect. This overexcitability of the nerve cells has the consequence that initially small groups of cells increasingly transmit too large impulses. As a result, larger nerve cell associations are stimulated at the same time and a regular firework of impulses begins, which manifests itself as an epileptic seizure. According to the experts, around one percent of the population in Germany suffers from epilepsy.

New starting point for the development of epilepsy drugs
It was already known from previous studies that the GABA receptors can have a significant influence on the development of epilepsy, not least because about 30 percent of the transmitter quantity in the central nervous system is attributable to these receptors. However, researchers worldwide have so far assumed that a defect directly at the GABA receptors itself was responsible for the disturbed signal transmission. As part of their current research, the scientists were able to Deisz from the Institute of Cell and Neurobiology of the Berlin Charité now disprove this theory for the development of epilepsy. Responsible are certain cellular ion transporters, which in turn affect the function of the GABA receptors, so the statement of the researchers. According to Dr. Deisz and colleagues may also explain why the prescribed epilepsy medications have so far failed many. „Our results not only show a key causative disorder (the transport proteins) in epilepsy“, But also provide a rationale for the failure of the drugs, said the Privatdozent Dr. med. Deisz. Thus, the researchers were confident in their publication, with their results „also found a starting point for the development of more effective drugs for the treatment of epilepsy.“ (Fp)

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Image: Dieter Schütz