TAAR1 is a promising drug target for schizophrenia and drug addiction: TAAR1 is a G-protein coupled receptor (GPCR) expressed in the dopaminergic and serotonergic systems of the brain, and regulates neurotransmission (13). It is an emerging drug target for schizophrenia and drug addiction (14-17). Atypical (second and third generation) antipsychotic drugs such as aripiprazole are effective for treating some symptoms of schizophrenia, such as hallucination and delusion, but better drugs are needed to improve the safety profile and efficacy, especially for symptoms such as flat affect and cognitive deficits (14). Drug addiction is a biopsychosocial disease that requires a patient-centered wraparound treatment, of which pharmacotherapy is an integral component (18). While buprenorphine/naloxone combination is effective for the treatment of opioid addiction, there is currently no effective pharmacotherapy for patients addicted to stimulants such as methamphetamine (16). TAAR1 is a promising drug target for methamphetamine addiction (19).

Human TAAR1 coding sequence was brought to the current Norimatsu lab from Oregon Health & Science University in pcDNA3 plasmid (hTAAR1_pcDNA3.str at the bottom, open with Ape Plasmid Editor). We also have a plasmid with TAAR1 coding sequence that we purchased from DNASU Plasmid Repository. The WT TAAR coding sequence (in pcDNA3.1) was transferred to pGHE (hTAAR1_pGHE.ape at the bottom).

In this project, the function of TAAR1 is compared to that of beta2-adrenergic receptor (b2AR) because they are homologous proteins and the latter has been extensively investigated. A plasmid containing a b2AR coding sequence was purchased from DNASU Plasmid Repository (ID HsCD00305465), and the coding sequence was transferred to pGHE (b2AR_pGHE.ape at the bottom). This transfer was achieved using HiFi DNA Assembly with 20 bp overlap.

We have built TAAR1 models and run simulated annealing simulations with it.

(See model below)

SnapGene Files