Hyperphenylalaninemia and serotonin deficiency in Dnajc12-deficient mice.

ABSTRACT: Serotonin exerts numerous neurological and physiological actions in the brain and in the periphery. It is generated by two different tryptophan hydroxylase enzymes, TPH1 and TPH2, in the periphery and in the brain, respectively, which are members of the aromatic amino acid hydroxylase (AAAH) family together with phenylalanine hydroxylase (PAH), degrading phenylalanine, and tyrosine hydroxylase (TH), generating dopamine. In this study, we show that the co-chaperone DNAJC12 is downregulated in serotonergic neurons in the brain of mice lacking TPH2 and thereby central serotonin. DNAJC12 has been described to regulate the stability of PAH and mutations in its gene cause hyperphenylalaninemia and neurological symptoms in patients. We show that DNAJC12 also binds and stabilizes TPH1 and TPH2 in

SUBMITTER: Cao Y 

PROVIDER: S-EPMC11655531 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature