Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
which in humans is encoded by the ''GABRA5''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
GABA
GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.
GA ...
is the major inhibitory neurotransmitter in the mammalian brain where it acts at
GABAA receptors, which are
ligand-gated
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...
chloride channel
Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Several ...
s. Chloride conductance of these channels can be modulated by agents such as
benzodiazepine
Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...
s that bind to the GABA
A receptor. At least 16 distinct subunits of GABA
A receptors have been identified. Transcript variants utilizing three different alternative non-coding first
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...
s have been described.
Subunit selective ligands
Recent research has produced several ligands which are moderately selective for GABA
A receptors containing the α
5 subunit. These have proved to be useful in investigating some of the side effects of benzodiazepine and nonbenzodiazepine drugs, particularly the effects on learning and memory such as
anterograde amnesia
In neurology, anterograde amnesia is the inability to create new memories after an event that caused amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. Thi ...
. Inverse agonists at this subunit have
nootropic
Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self ...
effects and may be useful for the treatment of cognitive disorders such as
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
.
Agonists
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QH-ii-066
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SH-053-R-CH3-2′F
Antagonists
*
α5IA
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Basmisanil (RG-1662, RO5186582): derivative of Ro4938581, negative allosteric modulator at GABA
A α
5, in human trials for treating cognitive deficit in
Down syndrome.
*
L-655,708
*
MRK-016
*
PWZ-029: moderate inverse agonist
*
Pyridazine
Pyridazine is an aromatic, heterocyclic, organic compound with the molecular formula . It contains a six-membered ring with two adjacent nitrogen atoms. It is a colorless liquid with a boiling point of 208 °C. It is isomeric with two other ...
s
*
Ro4938581
*
TB-21007
See also
*
GABAA receptor
References
Further reading
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External links
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Ion channels
Biology of bipolar disorder
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