Th-flox Mouse

Th, or tyrosine hydroxylase, is a key enzyme in the biosynthesis of catecholamines, including dopamine, norepinephrine, and epinephrine [1]. It catalyzes the conversion of L-tyrosine to L-DOPA, the rate-limiting step in catecholamine synthesis. The activity of TH is crucial for maintaining normal neurotransmission and physiological functions related to the sympathetic nervous system and central nervous system [1].

In Parkinson's disease, the activities and levels of mRNA and protein of TH are decreased, especially in dopamine neurons in the substantia nigra [1]. Hereditary GCH1 deficiency can lead to reduced levels of BH4, which in turn affects TH activity and dopamine levels [1]. Mild decreases in TH activity can result in symptoms of DOPA-responsive dystonia or juvenile Parkinsonism, while severe deficiencies cause severe neurological symptoms [1].

In conclusion, Th plays an essential role in catecholamine biosynthesis, and its dysfunction is closely associated with neurological disorders such as Parkinson's disease. Understanding the role of Th through studies, including those related to its decreased activity in disease-relevant models, provides insights into the pathophysiology of these disorders and may guide the development of potential therapeutic strategies.