Parkinson’s disease is the second most prevalent neurodegenerative disease after Alzheimer’s. It is characterized by motor symptoms, such as slow physical movements, shaking, muscle stiffness, and impaired balance and coordination, and in addition non-motor symptoms, such as changes in cognitive abilities and mood. Parkinson’s may develop over the course of decades, and by the time the motor symptoms appear allowing definitive diagnosis, it is too late for any effective intervention. Current therapies can help control symptoms, but there is no cure for Parkinson’s, and no therapy to stop or even slow disease progression.
It is presumed that alteration of the storage of dopamine, a neurotransmitter, may contribute to Parkinson’s disease. Disrupted storage of dopamine leads to the degeneration of dopamine neurons in the brain. Vesicular monoamine transporter 2 (VMAT2), a protein that helps regulate dopamine, may play a role. Among mice with 90 percent reduced VMAT2 levels, low levels of stored dopamine were observed in vesicles. These mice were further characterized by overexpression of α-synuclein, a protein in the brain previously associated with Parkinson’s disease, and exhibited symptoms similar to Parkinson’s disease.
Environmental risk factors such as pesticides, such as paraquat, and polychlorinated biphenyls (PCBs) (see previous post) have been linked to Parkinson’s and are strongly suspected to combine with genetic risk factors to increase risk of Parkinson’s and may be a point of therapeutic attack. Although many of these chemicals are now banned, they persist in the environment, causing continued human exposure. Since PCBs are known to inhibit storage of dopamine, characterizing the physiological effects of inhibited transport of dopamine may have important implications for understanding Parkinson’s disease.
There have been many studies showing links between exposure to pesticides and incidence of Parkinson’s disease. In a case-control study from 2009 the banned persistent pesticide β-HCH was double as often detectable in blood serum from Parkinson patients as in controls. Two years later the same authors found a dose-response relationship between HCH and Parkinson.
In a study from 2013 a connection between Parkinson’s and the banned fungicide benomyl was found. The mechanism was explained as blocking of the important enzyme: aldehyde dehydrogenase (ALDH) which protects dopamine.
Another study from 2014 by the same authors identified that pesticides maneb, ziram, trifluymizole, captanm, folpet and dieldrin also inhibited the enzyme. Participants who possessed a common genetic variant of the ALDH2 gene were more susceptible to the ALDH-blocking effects of the pesticides, and were two to six times more likely to develop Parkinson’s, compared with pesticide-exposed individuals who did not have the genetic variant.
A large Danish registry study from 2000 found a 30% higher risk of Parkinson’s disease among occupational groups employed with agriculture and horticulture. A newer case-control study of occupational factors and Parkinson’s is available.
A meta-analyse from 2013 of data from 104 studies supported the hypothesis that exposure to pesticides or solvents was a risk factor in Parkinson’s disease. Exposures to paraquat, maneb or mancozeb were associated with about a 2-fold increase in risk.