Celf Expression In Epilepsy Linked To Sodium Channels

Abstract

Evaluation of: Sun W, Wagnon JL, Mahaffey CL et al. Aberrant sodium channel activity in the complex seizure disorder of Celf4 mutant mice. J. Physiol. 591(1), 241–255 (2013). The choreographed expression of ion channels is critical for normal brain activity, as evidenced by the range of epilepsy syndromes associated with ion channel genetic variation. As large-scale sequencing efforts, such as Epi4K and EuroEPINOMICS, systematically deconstruct epilepsy genomes, it is likely that further progress will be made in our understanding of how ion channel dysfunction results in epilepsy. By contrast, our knowledge of non-ion channel genes in epilepsy is far less advanced, a problem frequently compounded by the lack of understanding of the basic neurobiology of these genes. Sun et al. address this shortcoming by providing an elegant account of how a key RNA metabolism gene, Celf4, gives rise to seizures by the regulation of axonal ion channels. This has implications for epilepsy genomics, where a priori knowledge of the gene networks that participate in seizure genesis is critical for bioinformatics filtering used to identify diagnostic and prognostic variants. The convergence on an ion channel target affirms their central role in seizure genesis but, more importantly, raises the idea that drugs that target key regulators such as CELF4 could be effective in epilepsy.

Keywords:

• Celf4
• epilepsy
• RNA-binding protein
• seizure
• sodium channel

Financial & competing interests disclosure

The authors would like to acknowledge the National Health and Medical Research Council and the Australian Research Council for grants and fellowships. The Florey Institute of Neuroscience and Mental Health is supported by the Victorian Government through the Operational Infrastructure Scheme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors would like to acknowledge the National Health and Medical Research Council and the Australian Research Council for grants and fellowships. The Florey Institute of Neuroscience and Mental Health is supported by the Victorian Government through the Operational Infrastructure Scheme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.