Regulation of gene expression and degradation of tyrosine hydroxylase in parkinson’s disease

Midbrain dopaminergic neurons play a central role in a wide range of behaviors, from attention and motivation to motor control and reinforcement. Dopaminergic systems, originating in the Ventral Tegmental Area (VTA) and in the substantia nigra pars compacta (SNpc), and mainly projecting to the ventral and dorsal striatum (mesostriatal pathway) and to the prefrontal cortex (mesocortical pathway), play a major motivational role in behavioral actions [1-3]. Dysfunction of the dopaminergic system is involved in neurological disorders such as Parkinson’s disease, Tourette’s syndrome, and schizophrenia, as well as in pituitary tumors [4]. Although the etiology of dopaminerelated disorders has been studied and molecular evidence for maintenance of a dopaminergic phenotype has been produced in the past quarter of century, they are not yet completely understood. The development of fundamental therapies for such diseases is expected. Here, I focus on Parkinson’s disease and present regulation of the gene expression of Tyrosine Hydroxylase (TH), the rate-limiting enzyme of dopamine biosynthesis. I also refer to the quality control system for the clearance of TH, and offer perspectives on the fundamental therapies for Parkinson’s disease.