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Acta Neurologica Belgica
Published in: Acta Neurologica Belgica 3/2020

01-06-2020 | Antiepileptic Drugs | Review article

Molecular insights into the role of AMPA receptors in the synaptic plasticity, pathogenesis and treatment of epilepsy: therapeutic potentials of perampanel and antisense oligonucleotide (ASO) technology

Authors: Saeid Charsouei, M. Reza Jabalameli, Amin Karimi-Moghadam

Published in: Acta Neurologica Belgica | Issue 3/2020

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Abstract

Glutamate is considered as the predominant excitatory neurotransmitter in the mammalian central nervous systems (CNS). Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are the main glutamate-gated ionotropic channels that mediate the majority of fast synaptic excitation in the brain. AMPARs are highly dynamic that constitutively move into and out of the postsynaptic membrane. Changes in the postsynaptic number of AMPARs play a key role in controlling synaptic plasticity and also brain functions such as memory formation and forgetting development. Impairments in the regulation of AMPAR function, trafficking, and signaling pathway may also contribute to neuronal hyperexcitability and epileptogenesis process, which offers AMPAR as a potential target for epilepsy therapy. Over the last decade, various types of AMPAR antagonists such as perampanel and talampanel have been developed to treat epilepsy, but they usually show limited efficacy at low doses and produce unwanted cognitive and motor side effects when administered at higher doses. In the present article, the latest findings in the field of molecular mechanisms controlling AMPAR biology, as well as the role of these mechanism dysfunctions in generating epilepsy will be reviewed. Also, a comprehensive summary of recent findings from clinical trials with perampanel, in treating epilepsy, glioma-associated epilepsy and Parkinson’s disease is provided. Finally, antisense oligonucleotide therapy as an alternative strategy for the efficient treatment of epilepsy is discussed.
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Metadata
Title
Molecular insights into the role of AMPA receptors in the synaptic plasticity, pathogenesis and treatment of epilepsy: therapeutic potentials of perampanel and antisense oligonucleotide (ASO) technology
Authors
Saeid Charsouei
M. Reza Jabalameli
Amin Karimi-Moghadam
Publication date
01-06-2020
Publisher
Springer International Publishing
Published in
Acta Neurologica Belgica / Issue 3/2020
Print ISSN: 0300-9009
Electronic ISSN: 2240-2993
DOI
https://doi.org/10.1007/s13760-020-01318-1

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