Unity Walk > The Parkinson Alliance Research Grants 2016

The Parkinson Alliance
is using its 2016 distribution to fund:

Does Air Pollution Increase the Risk of Parkinson’s Disease (PD)?

PROJECT TITLE:  Does Air Pollution Increase the Risk of Parkinson’s Disease (PD)?

Investigator/Author:  Jeff Bronstein MD, PhD

Objective:  The causes of PD are largely unknown.  Genetic factors appear to contribute approximately 20% to risk of developing the disease leaving environmental factors likely contributing the majority of risk.  A few environmental factors such as pesticides and head trauma almost certainly contribute to some individuals’ disease, these cannot explain the majority of risk that has yet been accounted for.  A recent study in Denmark found those exposed to high air pollution were at increased risk of developing PD and could account for a large percentage of the PD patients.  We have exciting preliminary data that support this theory.  Our objective in this proposal is to determine the biological plausibility of air pollution as a risk factor for PD and how it might cause it.

Methods/Design:  Diesel exhaust particles (DEP) is the major toxic constituent in air pollution and we will use an extract of DEP in our studies.  Zebrafish offer several advantages to other animal models including the fact that they are transparent and easily modified genetically.  Since alpha-synuclein accumulates in neurons in PD, we will test the effect of DEP on expression of alpha- synuclein using quantitative PCR and immunoassays.  We will also determine the effect of DEP on other proposed pathogenic pathways such as inhibition of protein breakdown, inflammation through microglia, and mitochondrial dysfunction.

Relevance to Treatment of Parkinson’s Disease:  There are still no treatments that slow or stop the progression of PD despite several attempts.  One reason for this is that we still do not know the causes of PD which is necessary to target specific pathways.  Based on extrapolation from the Danish study, more than half of all PD cases in Los Angeles could be caused by air pollution.  If this is found to be accurate, we will have identified new therapeutic targets.

Expected Outcome:  We anticipate that air pollution increases the risk of developing PD by more than one mechanism.   We have already found that DEP causes dopaminergic neuron loss in zebrafish and preliminary studies suggest that it increases alpha-synuclein expression.  Inflammation via microglia also likely contributes to the development of PD.  We will also determine if air pollution’s toxicity is dependent on alpha-synuclein since many disease modifying therapies are directed at lowering alpha-synuclein toxicity.

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