Post-translational and post-transcriptional mechanisms of activity regulation of tyrosine hydroxylase in the central nervous system – the effect of physical exercise

Abstract

Numerous studies indicate that dopamine (DA) is an important regulator of motor, psychological and cognitive functions. Maintaining the appropriate concentration of DA is a condition for the proper functioning of these functions. Tyrosine hydroxylase is involved in the control of DA synthesis. The aim of this study is to discuss the regulation of TH activity with the participation of three main mechanisms: 1) post-translational immediate regulation by phosphorylation of various sites in the enzyme molecule and 2) post-transcriptional with the participation of transcription factors and specific miRNAs, and 3) a DA mediated feedback mechanism. Important factors which are directly or indirectly involved in these regulations of TH activity and DA concentration are BDNF, testosterone, alpha-synuclein and protein kinases. A drastic reduction in DA levels in the extrapyramidal system causes drastic impairment of motor, psychological and cognitive functions. On the other hand, increased physical activity, in particular prolonged repetitive physical exercises by increasing the level of testosterone and BDNF in the blood, may activate signaling pathways dependent on them, increasing the activity of tyrosine hydroxylase, and thus increase the level of dopamine in the extrapyramidal system.