Application of induced pluripotent stem cells in epilepsy.
Mol Cell Neurosci
; 108: 103535, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32758699
ABSTRACT
Epilepsy is among the most common neurological disorders, affecting approximately 50 million people worldwide. Importantly, epilepsy is genetically and etiologically heterogenous, but several epilepsy types exhibit similar clinical presentations. Epilepsy-associated genes are being identified. However, the molecular pathomechanisms remain largely unknown. Approximately one-third of epilepsy is refractory to multiple conventional anti-epileptic drugs (AEDs). Induced pluripotent stem cells (iPSCs) provide an excellent tool to study the pathomechanisms underlying epilepsy and to develop novel treatments. Indeed, disease-specific iPSCs have been established for several genetic epilepsies. In particular, the molecular mechanisms underlying certain developmental and epileptic encephalopathies, such as Dravet syndrome, have been revealed. Modeling epilepsy with iPSCs enables new drug development based on the elucidated pathomechanisms. This can also be used to evaluate conventional AEDs and drug repurposing. Furthermore, transplanting neuronal cells derived from iPSCs into the brain has great potential to treat refractory epilepsies. Recent advances in iPSC technology have enabled the generation of neuronal organoids, or "mini brains." These organoids demonstrate electrophysiological activities similar to those of the brain and have the potential for extensive epilepsy research opportunities. Thus, the application of iPSCs in epilepsy provides insight into novel treatments based on the molecular pathomechanisms of epilepsy. In this review, we comprehensively discuss the studies conducted on iPSCs established for genetic epilepsy or epilepsies without major structural dysmorphic features.
Palavras-chave
Benign familial infantile epilepsy (BFIE); Differentiation; Drug screening; Embryonic stem cell (ES cells); Glia; High-throughput; Human pluripotent stem cells (human PSCs); Infantile spasm; Medial ganglionic eminence (MGE); Neuron; Ohtahara syndrome; Progenitor cells; Seizure; Severe myoclonic epilepsy in infancy (SMEI); West syndrome
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Epilepsia
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Células-Tronco Pluripotentes Induzidas
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Anticonvulsivantes
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article