Getting a Handle on Neuropharmacology by Targeting Receptor-Associated Proteins

Targeted therapy for neuropsychiatric disorders requires selective modulation of dysfunctional neuronal pathways. Receptors relevant to CNS disorders typically have associated proteins discretely expressed in specific neuronal pathways; these accessory proteins provide a new dimension for drug disco...

Full description

Saved in:
Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2017-12, Vol.96 (5), p.989-1001
Main Authors: Maher, Michael P., Matta, Jose A., Gu, Shenyan, Seierstad, Mark, Bredt, David S.
Format: Article
Language:English
Subjects:
accessory protein
Acetylcholine
acetylcholine receptor
AMPA receptor
Animals
auxiliary subunit
Central nervous system
Drug discovery
Drug efficacy
Drug therapy
Epilepsy
Excitability
Forebrain
GABA receptor
Humans
Ion channels
kainite receptor
ligand-gated ion channel
Mental disorders
Microscopy
Mutation
Nerve Tissue Proteins - drug effects
Neuromodulation
Neuropharmacology
Neurosciences
NMDA receptor
Pharmaceutical industry
Physiology
Proteins
Receptors, Neurotransmitter - drug effects
Rodents
Side effects
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Targeted therapy for neuropsychiatric disorders requires selective modulation of dysfunctional neuronal pathways. Receptors relevant to CNS disorders typically have associated proteins discretely expressed in specific neuronal pathways; these accessory proteins provide a new dimension for drug discovery. Recent studies show that targeting a TARP auxiliary subunit of AMPA receptors selectively modulates neuronal excitability in specific forebrain pathways relevant to epilepsy. Other medicinally important ion channels, gated by glutamate, γ-aminobutyric acid (GABA), and acetylcholine, also have associated proteins, which may be druggable. This emerging pharmacology of receptor-associated proteins provides a new approach for improving drug efficacy while mitigating side effects. Effective treatments for neuropsychiatric disorders require selective modulation of dysfunctional circuits. This review by Maher et al. outlines a strategy for targeting neurotransmitter receptor-associated proteins. This innovative pharmacological approach promises to enhance drug efficacy and minimize side effects.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2017.10.001