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Structural studies of serotonin receptor family

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Serotonin receptors, also known as 5-HT receptors, belong tothe G protein-coupled receptors (GPCRs) superfamily. Theymediate the effects of serotonin, a neurotransmitter that plays akey role in a wide range of functions including mood regulation,cognition and appetite. The functions of serotonin aremediated by a family of 5-HT receptors including 12 GPCRsbelonging to six major families: 5-HT1, 5-HT2, 5-HT4, 5-HT5,5-HT6 and 5-HT7. Despite their distinct characteristics and functions,these receptors’ subtypes share common structural featuresand signaling mechanisms. Understanding the structure, functionsand pharmacology of the serotonin receptor family is essentialfor unraveling the complexities of serotonin signalingand developing targeted therapeutics for neuropsychiatric disorders. However, developing drugs that selectively target specificreceptor subtypes is challenging due to the structural similaritiesin their orthosteric binding sites. This review focuses onthe recent advancements in the structural studies of 5-HT receptors,highlighting the key structural features of each subtypeand shedding light on their potential as targets for mentalhealth and neurological disorders (such as depression, anxiety,schizophrenia, and migraine) drugs.

Abstract

Serotonin receptors, also known as 5-HT receptors, belong tothe G protein-coupled receptors (GPCRs) superfamily. Theymediate the effects of serotonin, a neurotransmitter that plays akey role in a wide range of functions including mood regulation,cognition and appetite. The functions of serotonin aremediated by a family of 5-HT receptors including 12 GPCRsbelonging to six major families: 5-HT1, 5-HT2, 5-HT4, 5-HT5,5-HT6 and 5-HT7. Despite their distinct characteristics and functions,these receptors’ subtypes share common structural featuresand signaling mechanisms. Understanding the structure, functionsand pharmacology of the serotonin receptor family is essentialfor unraveling the complexities of serotonin signalingand developing targeted therapeutics for neuropsychiatric disorders. However, developing drugs that selectively target specificreceptor subtypes is challenging due to the structural similaritiesin their orthosteric binding sites. This review focuses onthe recent advancements in the structural studies of 5-HT receptors,highlighting the key structural features of each subtypeand shedding light on their potential as targets for mentalhealth and neurological disorders (such as depression, anxiety,schizophrenia, and migraine) drugs.

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