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Mitochondrial dysfunction in epilepsy
Journal article   Peer reviewed

Mitochondrial dysfunction in epilepsy

Divya S Khurana, Ignacio Valencia, Michael J Goldenthal and Agustín Legido
Seminars in pediatric neurology, v 20(3), pp 176-187
Sep 2013
PMID: 24331359

Abstract

Anticonvulsants - pharmacology Anticonvulsants - therapeutic use DNA, Mitochondrial - genetics Epilepsy - complications Epilepsy - genetics Epilepsy - metabolism Humans Mitochondria - drug effects Mitochondria - genetics Mitochondria - metabolism Mitochondrial Diseases - complications Mitochondrial Diseases - genetics Mitochondrial Diseases - metabolism Molecular Targeted Therapy Mutation
Epilepsy is the most common neurologic disorder worldwide and is characterized by recurrent unprovoked seizures. The mitochondrial (mt) respiratory chain is the final common pathway for cellular energy production through the process of oxidative phosphorylation. As neurons are terminally differentiated cells that lack significant regenerative capacity and have a high energy demand, they are more vulnerable to mt dysfunction. Therefore, epileptic seizures have been well described in several diseases such as mt encephalomyopathy, lactic acidosis, and stroke-like episodes and myoclonic epilepsy and ragged red fibers, which are caused by gene mutations in mtDNA, among others. Mutations in nuclear DNA regulating mt function are also being described (eg, POLG gene mutation). The role of mitochondria (mt) in acquired epilepsies, which account for about 60% of all epilepsies, is equally important but less well understood. Oxidative stress is one of the possible mechanisms in the pathogenesis of epilepsy resulting from mt dysfunction gradually disrupting the intracellular Ca(2+) homeostasis, which modulates neuronal excitability and synaptic transmission, making neurons more vulnerable to additional stress, and leading to energy failure and neuronal loss in epilepsy. Antiepileptic drugs (AEDs) also affect mt function in several ways. There must be caution when treating epilepsy in patients with known mt disorders as some AEDs are toxic to the mt. This review summarizes our current knowledge of the effect of mt disorders on epilepsy, of epileptic seizures on mt, and of AEDs on mt function and the implications of all these interactions for the management of epilepsy in patients with or without mt disease.

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Web of Science research areas
Clinical Neurology
Pediatrics
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