Tryptophan Hydroxylase: A Target for the Correction of Affective and Neurodegenerative Disorders

Tryptophan hydroxylase (TPH) is a key enzyme in the biosynthesis of serotonin, a neurotransmitter involved in the regulation of mood, emotional state, sleep, appetite, digestion, and cognitive functions. It plays a key role in the creation of a sense of well-being, reduction of anxiety and control of the response to stress. Imbalances in its levels are associated with many disorders, notably depression, anxiety disorders and migraines. This review examines the structural and functional aspects of the regulation of TPH activity with an emphasis on its isoforms, TPH1 and TPH2, which are responsible for serotonin synthesis in peripheral tissues and in neurons, respectively. Approaches to TPH regulation at the gene, protein, and enzymatic activity levels are discussed. The role of TPH in the pathogenesis of affective disorders such as depression, anxiety, attention deficit hyperactivity disorder and posttraumatic stress disorder is also discussed. Approaches to modulating TPH activity are proposed, including, for example, using calpain inhibitors.