RESUMEN

Epilepsy, characterized by recurrent seizures and abnormal brain discharges, is the third most common chronic disorder of the Central Nervous System (CNS). Although significant progress has been made in the research on antiepileptic drugs (AEDs), approximately one-third of patients with epilepsy are refractory to these drugs. Thus, research on the pathogenesis of epilepsy is ongoing to find more effective treatments. Many pathological mechanisms are involved in epilepsy, including neuronal apoptosis, mossy fiber sprouting, neuroinflammation, and dysfunction of neuronal ion channels, leading to abnormal neuronal excitatory networks in the brain. CK2 (Casein kinase 2), which plays a critical role in modulating neuronal excitability and synaptic transmission, has been shown to be associated with epilepsy. However, there is limited research on the mechanisms involved. Recent studies have suggested that CK2 is involved in regulating the function of neuronal ion channels by directly phosphorylating them or their binding partners. Therefore, in this review, we will summarize recent research advances regarding the potential role of CK2 regulating ion channels in epilepsy, aiming to provide more evidence for future studies.

RESUMEN

SLIT and NTRK-like protein-5 (SLITRK5) is one of the six members of SLITRK protein family, which is widely expressed in central nervous system (CNS). In brain, SLITRK5 plays important roles in neurite outgrowth, dendritic branching, neuron differentiation, synaptogenesis, and signal transmission of neurons. Epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. The pathophysiological mechanism of epilepsy remains unclear. Neuronal apoptosis, abnormal nerve excitatory transmission, and synaptic remodeling are thought to be involved in the development of epilepsy. To explore whether there is a potential relationship between SLITRK5 and epilepsy, we investigated the expression and distribution of SLITRK5 in patients with temporal lobe epilepsy (TLE) and a rat model of epilepsy. We collected cerebral cortex samples from patients with drug-refractory temporal lobe epilepsy, and a rat model of epilepsy induced by lithium chloride/pilocarpine was established. The ways of immunohistochemistry, double-immunofluorescence labeling and western blot have been used in our study to research the expression and distribution of SLITRK5 in the temporal lobe epilepsy patients and epilepsy animal model. All of the results have shown that SLITRK5 is mainly localized in the cell cytoplasm of neurons both in patients with TLE and in epilepsy model. In addition, compared with nonepileptic controls, the expression of SLITRK5 was upregulated in the temporal neocortex of TLE patients. And both in the temporal neocortex and hippocampus of pilocarpine-induced epilepsy rats, the expression of SLITRK5 was increased at 24 h after status epilepticus (SE), with a relatively high level within 30 days, and reached the peak on the 7th day after SE. Our preliminary results revealed that SLITRK5 may have a potential relationship with epilepsy, which may be a foundation for the further study of the underlying mechanism between SLITRK5 and epilepsy and the therapeutic targets of antiepileptic drugs.

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RESUMEN

SLIT and NTRK-like protein-5 (SliTrk5) is one of the six members of SliTrk protein family, which is widely expressed in the central nervous system (CNS), regulating and participating in many essential steps of central nervous system development, including axon and dendritic growth, neuron differentiation, and synaptogenesis. SliTrk5, as a neuron transmembrane protein, contains two important conservative domains consisting of leucine repeats (LRRs) located at the amino terminal in the extracellular region and tyrosine residues (Tyr) located at the carboxyl terminal in the intracellular domains. These special structures make SliTrk5 play an important role in the pathological process of the CNS. A large number of studies have shown that SliTrk5 may be involved in the pathogenesis of CNS diseases, such as obsessive-compulsive-disorder (OCD), attention deficit/hyperactivity disorder (ADHD), glioma, autism spectrum disorders (ASDs), and Parkinson's disease (PD). Targeting SliTrk5 is expected to become a new target for the treatment of CNS diseases, promoting the functional recovery of CNS. The purpose of this article is to review the current research progression of the role of SliTrk5 in CNS and its potential mechanisms in CNS diseases.

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