Role of Adenosine Kinase Inhibitor in Adenosine Augmentation Therapy for Epilepsy: A potential novel drug for epilepsy.
Curr Drug Targets. 2019 Oct 13;:
Authors: Wang X, Li T
Epilepsy, an ancient disease, is defined as an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological and social consequences of this condition. Antiepileptic drugs (AEDs) is currently used as first-line treatment for patients with epilepsy, however, around 36% patients are diagnosed into refractory epilepsy, which means two or more AEDs has been considered as failed after sufficiently correct usage. Unfortunately, it is unlikely that the improvement of efficacy of AEDs will be easily achieved, especially no AEDs shows efficacy in ceasing epileptogenesis. Consequently, several endogenous anticonvulsants attract to investigators and epileptologists, such as, galanin, cannabis and adenosine. <p> Astrogliosis is a neuropathological hallmark of epilepsy, whatever the etiology is, and astrogliosis is frequently associated with overexpression of adenosine kinase, which means downregulation of synaptic levels of adenosine. Consequently, adenosine is negatively regulated by adenosine kinase through astrocyte-based cycle. In the other hand, focal adenosine augmentation therapy, using adenosine kinase inhibitor, has been proved to be effective for reducing seizures in both animal models and in vitro human brain tissue resected from variety of etiology of refractory epilepsy patients. Except reducing seizures, adenosine augmentation therapy also can palliate co-morbidities, like sleep, cognition, or depression. Of importance, transgenic mice with reduced ADK were resistant to epileptogenesis induced by acute brain injury. In terms of translation, based on findings about adenosine-related epileptogenic mechanisms, the application into clinical practice seems to be feasible by molecular strategies that have been already experimentally implemented, including gene and RNA interference. <p> In the present review, we will focus on the evidence of ADK dysfunction in epileptic brain from human beings and animals, and review the role of ADK inhibitor in adenosine augmentation therapy and the underlying mechanism of prevention of epileptogenesis.
PMID: 31633474 [PubMed – as supplied by publisher]
Source: ncbi 2