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.
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 generat...Continue Reading
References
Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation
Citations
Methods Mentioned
Related Concepts
Related Feeds
Antisense Oligonucleotides: ND
This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.