The Function of Tyrosine Hydroxylase in the Normal and Parkinsonian Brain

Christopher      Tolleson; Daniel      Claassen

Abstract

Tyrosine hydroxylase (TH) is the rate limiting step in the biosynthesis of dopamine and other catecholamines. Differences have been noted in concentration and availability of this enzyme and its cofactors in disease states such as Parkinson’s disease (PD) which are subject to alterations in catecholamines. More evidence suggests in fact that TH may play a direct role in the pathogenesis of PD, especially through oxidative stress and pro-inflammatory mechanisms. Treatment for PD has classically involved maximizing endogenous dopamine by medicinal options that either replace dopamine or augment the dopaminergic pathway. The medications are unfortunately limited, given they are not curative and involve potential short-term and long-term side effects. Gene therapy in PD is a burgeoning field which provides a way to augment dopamine production, and potentially protect the dopaminergic neurons from further degeneration. Given its importance in dopamine catabolism and the possibility that it may contribute to pathogenesis, TH is one target of gene therapy. Further research into the regulatory mechanisms and function of TH are promising in improving gene therapy approaches as well as other treatment modalities.

Keywords: Gene therapy, oxidative stress, Parkinson’s disease, tyrosine hydroxylase.

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