Pharmacological chaperones (PCs)—small molecules that normalize the 3D structure of mutant protein molecules—are promising substances for pharmacological treatment of grave hereditary pathologies. In this study, possible chaperone-like effects of the Fe(II) with tris(1-pyrasolyl)methane complex, Fe(TPM)2Cl2, on the mutant 447R form of mouse tryptophan hydroxylase 2 (TPH2) in vitro and in vivo were investigated. The experiments were carried out on Balb/c mice homozygous for the mutant TPH2. This complex in concentrations of 0.01, 0.05 and 0.1 mM markedly increased the temperature (T50) and free energy (ΔG) of the mutant TPH2 thermal denaturation in vitro. Seven intramuscular administrations of 30 and 60 mg/kg of Fe(TPM)2Cl2 markedly increased the TPH2 activity in the midbrain of Balb/c mice. This increase in the TPH2 activity was not accompanied with an increase in the Tph2 gene mRNA and TPH2 protein levels. It is the first demonstration of chaperone-like activity of Fe(TPM)2Cl2. This complex is a promising chemical for correction of genetic alterations in TPH2 and the associated hereditary psychic disorders.
Terentieva et al. (Fri,) studied this question.