Affiliation:
1. Beijing Key Laboratory of Epilepsy, Beijing, China
Abstract
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) are currently used as first-line treatment for patients with epilepsy;
however, around 36% of patients are diagnosed with refractory epilepsy, which means two or more
AEDs have been considered as failed after sufficiently correct usage. Unfortunately, it is unlikely that
the improvement of the efficacy of AEDs will be easily achieved, especially since no AEDs show efficacy
in ceasing epileptogenesis. Consequently, several endogenous anticonvulsants attract investigators
and epileptologists, such as galanin, cannabis, and adenosine.
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 the astrocyte-based cycle. On 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 a variety of etiology of refractory epilepsy patients.
In addition to reducing seizures, adenosine augmentation therapy can also 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 of adenosinerelated
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.
In the present review, we will focus on the evidence of ADK dysfunction in the 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.
Funder
National Natural Science Foundation of China
Beijing Institute For Brain Disorders
Beijing Postdoctoral Research Foundation
Publisher
Bentham Science Publishers Ltd.
Subject
Clinical Biochemistry,Drug Discovery,Pharmacology,Molecular Medicine
Cited by
9 articles.
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