Tetrahydrobiopterin (BH4) treatment stabilizes tyrosine hydroxylase: Rescue of tyrosine hydroxylase deficiency phenotypes in human neurons and in a knock‐in mouse model

• Published in: Journal of inherited metabolic disease Vol. 47; no. 3; pp. 494 - 508
• Main Authors: Jung‐KC, Kunwar, Tristán‐Noguero, Alba, Altankhuyag, Altanchimeg, Piñol Belenguer, David, Prestegård, Karina S., Fernandez‐Carasa, Irene, Colini Baldeschi, Arianna, Sigatulina Bondarenko, Maria, García‐Cazorla, Angeles, Consiglio, Antonella, Martinez, Aurora
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2024; Blackwell Publishing Ltd
• Subjects: Animals; Biopterins - analogs & derivatives; Catalepsy; Catecholamines; Dan protein; Disease Models, Animal; Dopamine; Dopamine - metabolism; Female; Gene Knock-In Techniques; Heterozygosity; Homeostasis; Humans; Inhibitory postsynaptic potentials; iPSC‐derived neurons; Latency; Male; Mice; mice model; Neurons - metabolism; pharmacological chaperones; Phenotype; Phenotypes; Phenylketonurias - drug therapy; Phenylketonurias - genetics; Phenylketonurias - metabolism; Proteins; Tetrahydrobiopterin; tetrahydrobiopterin (BH4); Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - metabolism; tyrosine hydroxylase deficiency (THD); mice model; pharmacological chaperones; iPSC‐derived neurons; tyrosine hydroxylase deficiency (THD); dopamine; tetrahydrobiopterin (BH4)

Proteostatic regulation of tyrosine hydroxylase (TH), the rate‐limiting enzyme in dopamine biosynthesis, is crucial for maintaining proper brain neurotransmitter homeostasis. Variants of the TH gene are associated with tyrosine hydroxylase deficiency (THD), a rare disorder with a wide phenotypic spe...