One of the most important themes I’ve gathered from my time in my neurochemistry class is the theme of ambiguity when trying to determine the cause of a neurodegenerative disease. One of the best examples of this, in my opinion, is Parkinson’s Disease (PD). Last week, the scientific article we read explained the general mechanisms of Parkinson’s Disease as we know it today. However, I think the major take-away from the paper is the section toward the end titled, “Bringing it all together?” Let me explain why.
There have been major advances in the understanding of the mechanisms underlying dopaminergic cell death in PD. Some of these include, but are not limited to:
- Mitochondrial dysfunction
- Oxidative stress
- Altered protein handling
- Inflammation
- Altered proteolysis
- Excitotoxicity
The list continues to expand as we learn more and more about the disease. However, the sequence of events proposed to occur in PD has not been altered or changed in years. Furthermore, there has been a general trend of working to fit new pathological findings into the existing framework of conceptual belief. It is this trend that the section toward the end of the article brings up and questions. They argue it somewhat timidly, but I would like to state boldly that working new findings into an old framework without careful and critical thinking is not going to progress our knowledge of PD much further. In fact, it will somewhat stifle it.
There have been a number of studies in which cell death is initiated at a variety of points in the pathogenic cycle of PD. These studies themselves show the difficulty of distinguishing between “the horse and the cart” when it comes to causes and effects of PD. All of the mechanisms listed above could actually be the trigger or the effect of PD. Critically thinking about the results of these studies shows that the disease is more of a positive feedback loop rather than a linear progression of events, making it very difficult to pin point its beginning.
Because of the various starting points and effects of the disease, the author of the article was hinting at the idea that PD is less of a disease and more of a syndrome. The key mechanisms involved in PD that are listed above are would actually be separate pathogenic pathways representing different forms of what is currently known as PD. While the idea he leans toward may seem a bit radical, there are already many known forms of OD including:
- Sporadic PD
- Familial PD
- Parkin mutated PD
- Lewy body PD
Therefore, it only seems logical that, because a single trigger is not something within reach, PD is actually more of a syndrome with a handful of separate pathogenic pathways than a disease with a single cause. We are missing some key parts of the jigsaw puzzle that is PD, and are looking more closely at the downstream process that is the result of malfunctioning neuronal pathways. Because of this, I am emphasizing the idea that is presented toward the end of this article: because new findings and results do not fit perfectly into our existing framework of PD, it is important that each is taken into consideration as being a part of syndrome with multiple causes and manifestations.
