Title:Adenosine Dysfunction in Epilepsy and Associated Comorbidities
Volume: 23
Issue: 4
Author(s): Mengyi Guo and Tianfu Li*
Affiliation:
- Department of Brian Institute, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Key Laboratory of
Epilepsy Research, Sanbo Brain Hospital, Capital Medical University, Beijing100093, China
- Department of Neurology,
Center of Epilepsy, Beijing Institute for Brain Disorders, Sanbo Brain Hospital, Capital Medical University, Beijing100093,
China
Keywords:
Epilepsy, adenosine, comorbidity, adenosine kinase, epileptogenesis, adenosine augmentation therapy.
Abstract: Epilepsy, a complex neurological syndrome with dominant symptoms and various comorbidities,
affects over 70 million people worldwide. Epilepsy-related comorbidities, including
cognitive and psychiatric disorders, can impede therapy for epilepsy patients, leading to heavy burdens
on patients and society. Adenosine has an anti-epileptic and anticonvulsive function in the
brain. Several studies have shown that, through adenosine receptor-dependent and -independent
mechanisms, adenosine can influence the development and progression (epileptogenesis) of epilepsy
and its associated comorbidities. As the key enzyme for adenosine clearance, adenosine kinase
(ADK) can exacerbate epileptic seizures not only by accelerating adenosine clearance, but also by
increasing global DNA methylation through the transmethylation pathway. Therefore, adenosine
augmentation therapies for epilepsy can have dual functions in the inhibition of epileptic seizures
and the prevention of its overall progress. This review has three main purposes. First, we discuss
how maladaptive changes in the adenosine pathway affect the development and progress of epilepsy
in both receptor-dependent and receptor-independent ways. Second, we highlight the important
influence of associated comorbidities on the prognosis of epilepsy and explore the role of adenosine
in these comorbidities. Finally, we emphasize the potential of adenosine augmentation therapies
in restoring normal adenosine signaling in the epileptic brain. Such treatments could effectively
improve the prognosis of patients who are resistant to most antiepileptic drugs (AEDs), and thus
bring new challenges and opportunities in the treatment of epilepsy patients.
