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.
Keywords: Tyrosine hydroxylase, Parkinson’s disease, α-synuclein, gene therapy, dopamine synthesis, neuroprotection.
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