My previous knowledge on this week’s topic came from the movie “Love and Other Drugs.” In the movie, Anne Hathaway plays a woman in her early 20s living with the disease. I immediately think of the scenes where she is worn down physically and emotionally because she can’t do everyday things like drive to the pharmacy or simply to take care of herself. In this article, I got a deeper look into what happens in the brain of those with this PD.
First, the article talks about the need to look not only at the motor symptoms, but at the nonmotor symptoms (NMS) as well. In most cases, motor symptoms are expressed in the later stages of this neurodegenerative disease. These include difficulty speaking and swallowing, tremors, and an expressionless face. Specifically, damage to dopaminergic neurons in the substantia nigra leads to motor dysfunctions Some of the NMS include depression, sleeping issues, smelling impairment, rapid-eye movement, and cognitive issues. . By the time the physical symptoms occur, a lot of damage has already been done to the brain. If a method for NMS analysis can be fine-tuned, then current treatments, such as L-dopa and selegiline, may be more effective in slowing the progression of the disease.
PD is a complicated disease with a number of mechanisms for degeneration. The main categories are oxidative stress, mitochondrial stress, altered protein breakdown, excitotoxicity, and inflammation. The article states that inflammation is a general system reaction that may be the primary cause of dopaminergic loss. Inflammation is induced by the neurotoxins 6-hydroxydopamine (involved in the oxidative stress pathway) and MPTP (part of the mitochondrial stress pathway). All of these pathways seem to be in a complicated interplay. For example, oxidative stress may be induced by protein aggregation, specifically a-synuclein aggregation which are a component of Lewy bodies. Lewy bodies are a well-known marker of PD and are made up of unwanted proteins and cellular components which cluster together in the neurons. This oxidation may also lead to mitochondrial stress. However, mitochondrial stress increases reactive oxidative species (ROS), contributing to the oxidative stress. It is still unknown whether the pathways discussed are the initiators or downstream effects of some other cause of the disease. It may be that the specific mechanisms or combination of mechanisms are unique to each patient. Therefore, PD may never be reduced to one general cause.
Parkinson’s unlike other diseases we have looked at has more distinct environmental factors. The main environmental effectors are pesticides, exposure to metals, and solvents with the best evidence for pesticides. One herbicide, paraquat, mimics the neurotoxin precursor MPTP involved in mitochondrial stress. Paraquat is known to increase ROS which lead to oxidative stress. The mechanisms that the environmental effectors use highlight the combination of the pathways discussed. The environmental factors should not worry everyone. They are factors that require long-term exposure and are most commonly occupational risk factors. The combination of genetics and environment determine the expression of PD in each individual.
In “Love and Other Drugs,” Hathaway’s character attends a conference for Parkinson’s patients. The room is full of people who suffer from the same disease, but who could be affected by any combination of the mechanisms discussed above. Some people may have had a weak sense of smell or depression long before they saw any motor loss. Some people may be early onset patients affected by the parkin gene while others could have been victims of old age. That room may represent the spectrum of cases seen in Parkinson’s disease. Unfortunately, all that can be done currently is to treat the motor symptoms. If the nonmotor symptoms can be used to diagnose the early stages of the disease, drug interventions may slow the progression so that young cases like Hathway’s character don’t have to succumb to the fate of PD patients.
Article discussed found at:
http://www.sciencedirect.com/science/article/pii/S0891584913000282
Image found at:
https://www.michaeljfox.org/page.html?what-is-parkinsons-infographic
Parkinson's Disease: Another Neurological Mystery
