GABRA5
Encyclopedia
Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein
which in humans is encoded by the GABRA5 gene
.
is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABAA receptors, which are ligand-gated
chloride channel
s. Chloride conductance of these channels can be modulated by agents such as benzodiazepine
s that bind to the GABAA receptor. At least 16 distinct subunits of GABAA receptors have been identified. Transcript variants utilizing three different alternative non-coding first exon
s have been described.
. Inverse agonists at this subunit have nootropic
effects and may be useful for the treatment of cognitive disorders such as Alzheimer's disease
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the GABRA5 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
GABAGamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABAA receptors, which are ligand-gated
Ligand-gated ion channel
Ligand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger , such as a neurotransmitter.The binding site of endogenous ligands on LGICs...
chloride channel
Chloride channel
Chloride channels are a superfamily of poorly understood ion channels consisting of approximately 13 members.Chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell...
s. Chloride conductance of these channels can be modulated by agents such as benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s that bind to the GABAA receptor. At least 16 distinct subunits of GABAA receptors have been identified. Transcript variants utilizing three different alternative non-coding first exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
s have been described.
Subunit selective ligands
Recent research has produced several ligands which are moderately selective for GABAA receptors containing the α5 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 amnesiaAnterograde amnesia
Anterograde amnesia is a loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories...
. Inverse agonists at this subunit have nootropic
Nootropic
Nootropics , also referred to as smart drugs, brain steroids, memory enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration...
effects and may be useful for the treatment of cognitive disorders such as Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
Inverse agonists
- Ro-4938581
- α5IA
- pyridazines
- TB-21007TB-21007TB-21007 is a nootropic drug which acts as a subtype-selective inverse agonist at the α5 containing GABAA receptors.- References :...
- L-655,708L-655,708L-655,708 is a nootropic drug invented in 1996 by a team working for Merck, Sharp and Dohme, that was the first compound developed which acts as a subtype-selective inverse agonist at the α5 subtype of the benzodiazepine binding site on the GABAA receptor...
- PWZ-029PWZ-029PWZ-029 is a benzodiazepine derivative drug with nootropic effects. It acts as a subtype-selective, mixed agonist-inverse agonist at the benzodiazepine binding site on the GABAA receptor, acting as a partial inverse agonist at the α5 subtype and a weak partial agonist at the α3 subtype...
: moderate inverse agonist