Oxidant molecules generated during neuronal metabolism appear to play a significant role in the processes of
aging and neurodegeneration. Increasing experimental evidence suggests the noteworthy relevance of the intracellular
reduction-oxidation (redox) balance for the dopaminergic (DA-ergic) neurons of the substantia nigra pars compacta.
These cells possess a distinct physiology intrinsically associated with elevated reactive oxygen species production,
conferring on them a high vulnerability to free radical damage, one of the major causes of selective DA-ergic neuron
dysfunction and degeneration related to neurological disorders such as Parkinson’s disease. Tyrosine hydroxylase
(tyrosine 3-monooxygenase; E.C. 188.8.131.52; TH) activity represents the rate-limiting biochemical event in DA synthesis.
TH activity, metabolism and expression are finely tuned by several regulatory systems in order to maintain a crucial
physiological condition in which DA synthesis is closely coupled to its secretion. Alterations of these regulatory systems
of TH functions have indeed been thought to be key events in the DA-ergic degeneration. TH has seven cysteine residues
presenting thiols. Depending on the oxido-reductive (redox) status of the cellular environment, thiols exist either in the
reduced form of free thiols or oxidized to disulfides. The formation of disulfides in proteins exerts critical regulatory
functions both in physiological and in pathological conditions when oxidative stress is sustained. Several reports have
recently shown that redox state changes of thiol residues, as consequence of an oxidative injury, can directly or indirectly
affect the TH activity, metabolism and expression.
The major focus of this review, therefore, is to report recent evidence on the redox modulation of TH activity and
expression, and to provide an overview of a cellular phenomenon that might represent a target for new therapeutic
strategies against the DA-ergic neurodegenerative disorders.