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Kulikova, Elizabeth A; Kulikov, Alexander V
Expert opinion on therapeutic targets, 08/2019, Letnik: 23, Številka: 8Journal Article
: Tryptophan hydroxylase 2 (TPH2) is the key, rate-limiting enzyme of serotonin (5-HT) synthesis in the brain. Some polymorphic variants of the human gene are associated with psychiatric disorders. : This review focuses on the mechanisms underlying the association between the TPH2 activity and behavioral disturbances in models of psychiatric disorders. Specifically, it discusses: 1) genetic and posttranslational mechanisms defining the TPH2 activity, 2) behavioral effects of knockout and loss-of-function mutations in the mouse gene, 3) pharmacological inhibition and the activation of the TPH2 activity and 4) alterations in the brain TPH2 activity in animal models of psychiatric disorders. We show the dual role of the TPH2 activity: both deficit and excess of the TPH2 activity cause significant behavioral disturbances in animal models of depression, anxiety, aggression, obsessive-compulsive disorders, schizophrenia, and catalepsy. : Pharmacological chaperones correcting the structure of the TPH2 molecule are promising tools for treatment of some hereditary psychiatric disorders caused by loss-of-function mutations in the human gene; while some stress-induced affective disorders, associated with the elevated TPH2 activity, may be effectively treated by TPH2 inhibitors. This dual role of TPH2 should be taken into consideration during therapy of psychiatric disorders.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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