TAARs belong to the family of G protein coupled receptors (GPCRs).
TAARs (trace amine associated receptors) are a class of G protein-coupled receptors that were discovered in 2001. In humans, the TAARs genes are located on chromosome 6 in region q23.1, a region that is associated with mental disorders. In total, humans have 9 TAARs genes, three of which (TAAR3, TAAR4 and TAAR7) have undergone pseudogenesis. Six genes are functional, encoding TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, TAAR9, respectively. TAAR1 is the most well described and widely represented in the central nervous system and other organs of humans and other mammals, while the remaining TAARs are represented mainly in the olfactory epithelium, although in recent years evidence of their role outside this region has been accumulating.
TAAR 1
The most studied of all TAARs is TAAR1. In the human brain and model animals, it is present in areas responsible for the production of dopamine, serotonin, norepinephrine and glutamate - key neurotransmitters involved in the pathogenesis of diseases such as schizophrenia, depression, addictive behavior, and Parkinson's disease. Current scientific evidence suggests that selective TAAR1 agonists are capable of modulating the synthesis and transmission of dopamine, serotonin and glutamate, and therefore this receptor has become a target of modern antipsychotics undergoing clinical trials.
In addition to the central nervous system, TAAR1 is also present outside it, showing the most significant expression in the pancreas, stomach, intestines, blood leukocytes, thyroid gland, and placenta.
TAAR1 agonists have reached clinical trial level in the USA, Japan and Switzerland for the following clinical nosologies: schizophrenia, depression, anxiety and psychosis in Parkinson's disease. We are developing similar substances in Russia.
In addition to the central nervous system, TAAR1 is also present outside it, showing the most significant expression in the pancreas, stomach, intestines, blood leukocytes, thyroid gland, and placenta.
TAAR1 agonists have reached clinical trial level in the USA, Japan and Switzerland for the following clinical nosologies: schizophrenia, depression, anxiety and psychosis in Parkinson's disease. We are developing similar substances in Russia.
TAAR 2
As all TAARs except TAAR1, TAAR2 is found in the olfactory epithelium. Ligands for TAAR2 have not yet been identified either among known endogenous trace amines or among other volatile amines.
It is worth noting that, like TAAR5, TAAR2 is present in the limbic areas of the brain, which receive olfactory information. In behavioral experiments, TAAR2 knockout (TAAR2-KO) mice showed decreased depressive behavior, with TAAR2-KO mice exhibiting increased dopamine levels and an increased number of dopaminergic neurons in the brain and increased neurogenesis in adulthood.
Thus, the role of TAAR2 in the regulation of the dopamine system of the brain, electrophysiological activity of neurons, and neurogenesis in adult animals cannot be excluded.
It is worth noting that, like TAAR5, TAAR2 is present in the limbic areas of the brain, which receive olfactory information. In behavioral experiments, TAAR2 knockout (TAAR2-KO) mice showed decreased depressive behavior, with TAAR2-KO mice exhibiting increased dopamine levels and an increased number of dopaminergic neurons in the brain and increased neurogenesis in adulthood.
Thus, the role of TAAR2 in the regulation of the dopamine system of the brain, electrophysiological activity of neurons, and neurogenesis in adult animals cannot be excluded.
TAAR 5
TAAR5 was initially described as a receptor in the olfactory epithelium that captures volatile trace amines (trimethylamine, dimethylamine), but its expression was also found in the limbic areas of the brain of model animals responsible for the analysis of olfactory information. Mice knockout for this receptor (TAAR5-KO) demonstrated reduced depressive and anxious behavior in behavioral tests, with improved cognitive abilities. Intriguing data were found to indicate an increase in neurogenesis and the number of dopaminergic neurons in the brain of TAAR5-KO mice.
Thus, TAAR5 is a promising target for the development of selective antagonists that may help treat depression, negative symptoms of schizophrenia and Parkinson's disease.
Thus, TAAR5 is a promising target for the development of selective antagonists that may help treat depression, negative symptoms of schizophrenia and Parkinson's disease.
TAAR 6
TAAR6 expression has been found in several regions of the human brain, including the amygdala and hippocampus, basal ganglia, frontal cortex, and substantia nigra. It is worth noting that TAAR6 levels may exceed those of the most extensively studied member of the TAAR family, TAAR1. However, the consequences of functional activation of TAAR6 still remain unclear. Like TAAR2, selective ligands for TAAR6 have not yet been discovered, although it is proposed to be activated by tertiary amines and/or diamines.
Studies in TAAR6 knockout (TAAR6-KO) animal models have shown changes in the functioning of the serotonergic system, as well as a decrease in anxiety behavior in various tests.
Studies in TAAR6 knockout (TAAR6-KO) animal models have shown changes in the functioning of the serotonergic system, as well as a decrease in anxiety behavior in various tests.
TAAR 8
In addition to the olfactory system, TAAR8 expression has been found in the human amygdala, white blood cells, gastrointestinal tract, and tumor cells. Ligands for this receptor have not been identified, although it is assumed that they may be diamines such as putrescine and cadaverine.
There is evidence of changes in the expression pattern of TAAR8 as human pluripotent stem cells differentiate into dopaminergic neurons.
Interestingly, TAAR8 expression has a strong inverse correlation with breast cancer severity and is also decreased in melanomas compared to benign skin lesions (nevi). However, the possible prognostic and pathogenetic role of TAAR8 and other TAARs remains to be elucidated.
There is evidence of changes in the expression pattern of TAAR8 as human pluripotent stem cells differentiate into dopaminergic neurons.
Interestingly, TAAR8 expression has a strong inverse correlation with breast cancer severity and is also decreased in melanomas compared to benign skin lesions (nevi). However, the possible prognostic and pathogenetic role of TAAR8 and other TAARs remains to be elucidated.
TAAR 9
TAAR9 is one of the least studied members of the TAARs family, with unidentified endogenous ligands and unknown roles in the central nervous system and periphery. It is suggested that the molecular structure of TAAR9 is suitable for recognizing diamines and polyamines (putrescine, cadaverine, spermine and spermidine). In model animals knockout for TAAR9 (TAA9-KO), a decrease in total cholesterol levels was detected, and changes in the composition of the large intestinal microbiota were also noted, which may indicate the contribution of this receptor to metabolic processes and intestinal functioning.
Contact
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Sredniy prospect
Vasilievsky Island, 88
Saint Petersburg,
Russia,
199106
info@taargain.com
Sredniy prospect
Vasilievsky Island, 88
Saint Petersburg,
Russia,
199106