Study, Jul/18: "Structure of a human synaptic GABAA receptor"

https://www.ncbi.nlm.nih.gov/pubmed/29950725

2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27

Structure of a human synaptic GABAA receptor

Zhu S1, Noviello CM1, Teng J1, Walsh RM Jr1, Kim JJ1, Hibbs RE2.

Author information

1

    Departments of Neuroscience and Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.

2

    Departments of Neuroscience and Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA. ryan.hibbs@utsouthwestern.edu.

Abstract

Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABAA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABAA receptor is also a prolific target for therapeutic, illicit and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and ethanol. Here we present high-resolution cryo-electron microscopy structures of the human α1β2γ2 GABAA receptor, the predominant isoform in the adult brain, in complex with GABA and the benzodiazepine site antagonist flumazenil, the first-line clinical treatment for benzodiazepine overdose. The receptor architecture reveals unique heteromeric interactions for this important class of inhibitory neurotransmitter receptor. This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness.

PMID:

    29950725

DOI:

    10.1038/s41586-018-0255-3

https://www.ncbi.nlm.nih.gov/pubmed/29950725

 

2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27

 

Structure of a human synaptic GABAA receptor

 

Zhu S1, Noviello CM1, Teng J1, Walsh RM Jr1, Kim JJ1, Hibbs RE2.

Author information

 

1

    Departments of Neuroscience and Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.

2

    Departments of Neuroscience and Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA. ryan.hibbs@utsouthwestern.edu.

 

Abstract

 

Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABAA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABAA receptor is also a prolific target for therapeutic, illicit and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and ethanol. Here we present high-resolution cryo-electron microscopy structures of the human α1β2γ2 GABAA receptor, the predominant isoform in the adult brain, in complex with GABA and the benzodiazepine site antagonist flumazenil, the first-line clinical treatment for benzodiazepine overdose. The receptor architecture reveals unique heteromeric interactions for this important class of inhibitory neurotransmitter receptor. This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness.

 

PMID:

    29950725

DOI:

    10.1038/s41586-018-0255-3

Thanks for posting

“This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness.”

That’s an oxymoron 

Nothing rationally therapeutic about targeting a GABAaR in any way , shape, or form.

I guess they will always continue to think that they can tinker around with this receptor without consequence.