Tryptophan hydroxylase as novel target for the treatment of depressive disorders.
Serotonin (5-HT) is a monoamine implicated in a variety of physiological processes that functions either as a neurotransmitter or as a peripheral hormone. Pharmacological and genetic studies in humans and experimental animals have shown that 5-HT is important for the pathophysiology of depressive disorders. The 5-HT system is thus already a main target for the therapy of these diseases. The peripheral and cerebral biosynthesis of 5-HT is initiated by two distinct tryptophan hydroxylases: TPH1 and TPH2. This duality of the serotonergic system and the existence of a brain-specific TPH isoform provide a promising new target for pharmacological intervention with higher selectivity and specificity and, therefore, possibly with reduced side effects and increased efficiency. This paper summarizes the data which support TPH2 as novel drug target and discusses strategies for its pharmacological exploitation.
Matthes
Susann
S
Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
Mosienko
Valentina
V
Bashammakh
Saleh
S
Alenina
Natalia
N
Bader
Michael
M
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics; D016896:Treatment Outcome; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*
D000928:Antidepressive Agents; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase