Parkinson Disease is a devastating neurodegenerative disease that affects approximately 1,000,000 US citizens. The causes of this disease are largely unknown and the current therapies do not offer long-term benefits. There is currently no cure for Parkinson Disease. Unraveling the causes of Parkinson Disease is essential for indentifying risk factors and new therapies for this disease. One way of finding the causes of this disease is by the discovering unique and potentially toxic chemistries in the brain of Parkinson Disease patients. Recently, it was discovered that these patients have the capacity to produce bleach in affected regions of their brains. The brain is poorly equipped to handle bleach production, and the amounts of bleach formed are sufficient to compromise the viability of the vulnerable dopaminergic neurons in Parkinson Disease. Bleach is a highly reactive compound which begs the question of how this agent specifically kills dopaminergic neurons. We have discovered bleach reacts very rapidly with dopamine to produce a range of chlorinated products. Some of these products may be specifically absorbed by dopaminergic neurons at concentrations that result in the death of these cells. Some chlorinated forms of dopamine are also highly stable, and therefore the detection of these molecules may provide a powerful index for bleach production in brains of Parkinson Disease patients. Thus, the goals of the proposed studies are characterize the products of the reaction of bleach and dopamine and to determine the mechanisms by which the resulting chlorinated products are toxic to dopaminergic neurons.
Parkinson Disease is a devastating neurodegenerative disease of predominantly unknown causes that affects approximately 1,000,000 US citizens. Bleach is formed in the brains of these patients and may react with dopamine to form selective poisons of the dopaminergic neurons affected in this disease. Therefore, our goals are to characterize the reaction products of bleach and dopamine and to test one mechanism for the selective toxicity of chlorinated dopamine to dopaminergic neurons.
|Kalogiannis, Mike; Delikatny, E James; Jeitner, Thomas M (2016) Serotonin as a putative scavenger of hypohalous acid in the brain. Biochim Biophys Acta 1862:651-661|
|Jeitner, T M; Kalogiannis, M; Patrick, P A et al. (2015) Inflaming the diseased brain: a role for tainted melanins. Biochim Biophys Acta 1852:937-50|
|Jeitner, Thomas M (2014) Optimized ferrozine-based assay for dissolved iron. Anal Biochem 454:36-7|
|Jeitner, Thomas M; Cooper, Arthur J L (2014) Inhibition of human glutamine synthetase by L-methionine-S,R-sulfoximine-relevance to the treatment of neurological diseases. Metab Brain Dis 29:983-9|
|Jeitner, Thomas M; Kalogiannis, Mike; Mathew, Jim (2013) Preparation of 2-nitro-5-thiobenzoate for the routine determination of reagent hypochlorous acid concentrations. Anal Biochem 441:180-1|