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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Research Grants (R03)
Project #
5R03NS074286-02
Application #
8269909
Study Section
Neural Oxidative Metabolism and Death Study Section (NOMD)
Program Officer
Sieber, Beth-Anne
Project Start
2011-06-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$69,720
Indirect Cost
$19,720
Name
Winthrop-University Hospital
Department
Type
DUNS #
065937856
City
Mineola
State
NY
Country
United States
Zip Code
11501
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