International Journal of Molecular and Cellular Medicine (IJMCM)

Trace amine-associated receptor 1 (TAAR1) is a classical representative of G-protein coupled receptors (GPCRs). It is widely distributed in the mammalian brain, potentially plays an important role in modulating neurotransmitter functions and may regulate synaptic transmission and neuronal activity. Studies on TAAR1 signaling pathways were reviewed to identify the potential of TAAR1 as a novel target for neuroprotection and neurorepair. TAAR1 realizes effects through binding to the G-protein subunits Gas or Ga13. The target of Gas is PKA and the target of Ga13 is RhoA. Among the RhoA-mediated effects of TAAR1, effects on MAPK/ERK pathway kinases, AMPA and NMDA glutamate receptors and CREB factor have been investigated. RhoA-mediated effects include effects on the internalization of DAT and EAAT3, neuronal transporters of dopamine and glutamate. A G-protein independent pathway is mediated by β-arrestin and is probably related to the formation of the TAAR1-D2R heterodimer. The modulatory effect of TAAR1 on neurotransmitter systems allows us to consider TAAR1 agonists as potential therapeutic agents for the treatment of neurodegenerative diseases and psychiatric disorders, as well as neuroprotectors in ischemic brain damage.