Tryosine Hydroxylase as a Cytotoxic Protein in Parkinson’s Disease

Donald M. Kuhn, Ph.D.
Wayne State University School of Medicine, Dept. of Psychiatry and Behavioral Neurosciences

A study of possible causes of PD has been undertaken by Dr. Donald M. Kuhn (Wayne State University), since identification(s) would logically lead to more appropriate preventive and/or symptomatic treatment. Dr. Kuhn's project is focused on endogenous (within the body) neurochemical factors, since it is known that when the chemical lacking in PD brains, dopamine (DA), breaks down due to instability, other reactive chemicals are released as by-products; i.e., superoxide radicals, nitric oxide, etc. These can cause damage in their own rights and react to remaining DA, converting it to quinones that can lower the brain's defense mechanisms. Dr. Kuhn found that quinones bind to tyrosine hydroxylase (the enzyme that converts levodopa to dopamine), depleting the brain of TH even more than it already has been by PD. Cell cultures injected with this modified TH showed immediate damage and loss of function. The next step would be to determine the role(s) of DA quinones as well as prevent their formation