Current status of tyrosine hydroxylase in management of Parkinson's disease

Abstract

Tyrosine hydroxylase (TH) is the rate limiting enzyme responsible for converting tyrosine to L-DOPA in the dopamine synthesis pathway. The pathophysiology of Parkinson's disease (PD) is largely due to the nigrostriatal dopaminergic system, with a decrease in TH activity, TH synthesis and TH mRNA in the striatum of PD and animal experimental models. TH is thus one of the main targets for gene therapy in PD. TH activity variations during L-DOPA and new antiparkinsonian treatments have been extensively studied. Pharmacological trials with neuroprotective treatments could modify these variations, suggesting a direct involvement of TH cells in the neurodegenerative process. α- Synuclein, the main component of Lewy bodies regulates the production of dopamine through its interaction with TH. Over-expression of α-synuclein reduces the levels of TH mRNA and protein in the brain and in this way links the histological description of PD and its pathological biochemistry.