In this thesis, we investigated serine phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, to increase the enzymatic activity and dopamine production in the framework of Parkinson’s disease. The progressive degeneration of midbrain dopaminergic neurons in Parkinson’s disease causes decreased dopamine release into the striatum, which results in a variety of motor dysfunctions. Targeting tyrosine hydroxylase, by phosphorylation of serine at position 40 (Ser40), lifts the inhibitory interaction of dopamine with the catalytic region within the enzyme and makes the enzyme more active. This mechanism would result in the replenishment of decreasing levels of dopamine, improving neuronal dopamine signaling and alleviating initial motor symptoms. As such, we investigated Ser40 phosphorylation in dopaminergic MN9D cells and in the mouse striatum, which is regulated by upstream cAMP-dependent pathways. We additionally tested the exogenous application of L-DOPA on the phosphorylation state of tyrosine hydroxylase. We finally explored upstream targets that are able to increase tyrosine hydroxylase activity specifically in nigrostriatal neurons, through adenylyl cyclases, G-protein coupled receptors and natriuretic peptide receptors that modulate cAMP- and cGMP-dependent signaling routes. We found interesting leads that are potential therapeutic options for Parkinson’s disease, to alleviate initial motor symptoms with reduced side-effects and thus enhancing the quality of life of patients suffering from this debilitating disease.