Is Parkinson’s Disease Genetic? How Do Genes Play a Role in Parkinson’s?

Given the rapidly advancing field of bio engineering, and the fact that genetics has crept its way into practically every disease over the last few years, asking if a condition is genetic has become a common and safe habit. In many ways, given the discoveries that have followed the advancements in the sciences that have helped shape our understanding of the field of genetics and genomics, it has even become safe to assume that everything that is taking place within the human system is, in one way or another, genetic.

As such, asking whether diseases such as Alzheimer’s disease,Gaucher disease and Parkinson’s Disease (PD) is genetic and how genes play a role in the disease is justified. However, before opening that proverbial can of worms, so to say, having a proper understanding of what the condition actually does as well as the risk factors and the types of symptoms it brings along with it would be very helpful. PD is relatively widespread compared to other neuro degenerative diseases—it is the second most common of them all, just after Alzheimer’s disease. Approximately seven million people worldwide and one million in the US are affected by PD, a condition that is definitely more common in the elderly as well as males. Generally speaking, PD that begins after the age of 50 is considered to be late-onset, while PD before that age is referred to as early-onset.

The history of PD dates back to an essay that was written in 1817 by a British apothecary, James Parkinson. The essay, titled An Essay on the Shaking Palsy, which lines out all of the typical PD symptoms (tremors, abnormal posture,and gait, paralysis as well as weak muscle strength), together with the fact that it is a progressively worsening condition. While the condition was then known as Paralysis agitans(shaking palsy), it was not until 1865 that it was coined “Parkinson’s Disease” by William Sanders. The term was then later popularized by the French neurologist, Jean-Martin Charcot.

PD affects cell functioning within the brain, which puts it into the category of neuro degenerative diseases. More specifically, it affects the nervous system, and that is manifested in the body as tremors, shaking, slow movement, balance problems as well as stiffness. Even more specifically, it is a disorder of the central nervous system whose effects are mostly exhibited on the motor system. Issues with movement that are attributable to PD are due to not enough dopamine in a specific region of the brain, namely the substantia nigra. This, on the other hand, is because of cell death that is not quite fully understood. However, some research has indicated that an accumulation of proteins into Lewy bodies within the neurons might be responsible. The proteins that accumulate to make up Lewy bodies are called alpha-synuclein, and the highest accumulations of it are found within the brain. Furthermore, PD is considered to be a progressive neuro degenerative disorder, which means it starts out as mild and becomes worse over time.

In terms of genetics

In terms of genetics, not much is yet known about PD and its genetic story. Add to that that very few PD patients have a family history of it, which means that it is not typical for it to be inherited, either.

However, mutations in several genes that are associated with PD in terms of the outcomes they cause have been found. These include leucinerich repeat kinase 2 (LRRK2), Parkinsonism associated deglycase(PARK7), PTEN induced kinase 1 (PNK1), parkin RBR E3 ubiquitin protein ligase (PRKN) and synuclein alpha (SNCA). Also, mutations in the aforementioned genes have been associated with inherited forms of PD. Overall, while it remains unknown just how these genetic irregularities cause PD specifically, a general trend has been found that mutations in the aforementioned genes are associated with familial cases of PD even though they are incredibly rare.

Furthermore, in terms of genetic testing for PD patients, some research has related mutations in the PNK1 gene to early-onset PD (before the age of 30), and individuals getting tested for PNK1 mutations can only expect meaningful results if they have been diagnosed with PD before the age of 30. It has been found that a very small percentage of those who get PD that early in life carry the mutation.

So, to get back to the original question of whether PD is actually genetic or not, the risk factors, and if and how genes play a role, the answer is that it is unsure. There are very few cases of PD that are a result of genetic mutations, and hereditary causes are very rare (although research does indicate that if you have family members who have suffered from it, you are much more prone to it yourself.)Approximately 15 percent of all PD cases are associated with a previous family history. For the rest of the cases, the cause is typically unknown. There are a few instances of PD being hereditary and that is typically due to a gene that codes for alpha-synuclein. However, some research does point to the fact that there is an interplay between genes and environment that may be a trigger of PD.

Keep in mind also that simply inheriting a copy of genetic mutation is not enough to get PD. It is a combinatorial approach, rather, whereby other mutations have to be taken into consideration as well as lifestyle choices, together with a few other environmental factors.

Furthermore, given the uncertainty about what actually causes PD, it is difficult to suggest activities that may be protective against it.

Lastly, much of what we know about PD today can be attributed to a few famous individuals who have been diagnosed and who have shed much light on the condition. The most famous cases of PD are Michael J. Fox, Davis Phinney as well as boxer Muhammad Ali—all three have been diagnosed with early onset PD.

Laura Day
 

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