Cobbers on the Brain

The Parkinson’s in Me
I was sitting in my college dorm room during my sophomore year at Concordia. My desk was cluttered as usual with the week’s homework. My phone began to ring; it was my mother. Cheerily, I answered with, “Hello!” expecting her happy response in return. But the happiness was not to be heard, and she solemnly asked how I was doing. I could immediately tell that something was wrong, and over the next few minutes, she informed me that my beloved uncle had been diagnosed with Parkinson’s disease.
That evening I cried, wondering how his life would change over the coming years. I wondered how I could support him, but vowed that we would not treat him differently simply because his developing condition had been given a name by a physician. In the back of my mind, I could not help but think of how similar I am to my uncle, bearing more of a resemblance to him than most of my family members. As a scientist myself, I know that external looks certainly do not have to be genetically linked to a disease such as this, but I could not avoid pondering the thought that our family medical history now included Parkinson’s disease.
I have heard that there comes a time in medical school in which too much knowledge is dangerous. After learning about a plethora of diseases, each medical student will introspectively become more aware of the body and will realize that he or she has all of them! This is exactly how I felt. Suddenly, my morning hand shakiness during class (from lack of protein and energy because breakfast had not fully digested) and an occasional drool during the night were not natural occurrences, but instead were pre-emptive indicators for Parkinson’s disease.
While it is silly to think this, especially in my young age because Parkinson’s disease is almost entirely seen later in life, these are the types of conclusions that make medical education so important in the general public. I cannot say that I really ever knew more than a trivial fact or two, and even after my uncle had been diagnosed, I hardly knew enough to begin judging my personal dispositions toward the disease.
But this week during my neurochemistry class, we delved into what is currently known about Parkinson’s disease in relation to what is actually occurring in the body. Overall, we learned that it is incredibly complex, and there are many avenues and factors that seem to contribute. I will try to focus on a couple that seemed to be front and center. The first is a little protein called Parkin. This busy protein is like a handyman in the neurons of your brain. Parkin’s job is to travel around the cell and physically mark things that don’t appear to be functioning properly or that should be cleaned up. This process is called ubiquitination, and it is Parkin’s way of telling your cell, “Hey, take out the trash!” = (Get rid of those toxins!) or “This needs fixing.” = (Patch up this cellular machine!) In one of the genetic forms of Parkinson’s disease, Parkin ends up being inactivated, so these cellular toxins accumulate, and the cell has trouble recycling some of its damaged organelles. This causes the eventual death of the neuron, and I’m sure you can imagine that the death of neurons in your brain would not be ideal.
A second aspect that seemed to be particularly important was another protein called alpha-synuclein which I will refer to from now on as AS. Normally, AS is found at the connections between neurons and helps to mediate the use of neurotransmitters, which are signaling molecules that your nerves use to communicate information. Anyway, for a variety of reasons (eg. mutation, damage, oxidative stress), in Parkinson’s patients, AS proteins tend to stick to each other in clumps which we have called Lewy bodies. Because they are large and “in the way” of your normal cell processes, they get transported outside of the cell where they are thought to accumulate and play a role in causing the death of the neurons.
As I mentioned before, Parkinson’s disease is incredibly complex, and scientists are still working vigorously to unearth its secrets. In the meantime, I am investing myself in a medical research career, and perhaps I too will one day work in this fight against Parkinson’s disease. I already was motivated by my own ambitions, but my uncle’s diagnosis two years ago has made this into a personal battle. Perhaps his condition developed naturally over time, or maybe he was pre-disposed by the genes in his DNA. In either case, I approach the situation with maturity, as it is simply another obstacle in the game of life with which to deal. If Parkinson’s disease is meant to appear in my future, then I will treat it with the respect it deserves. But to live life thinking about the obstacles that may happen is to live in fear─ I choose to live in control with the courage to overcome. Will you take a leap of faith to tackle the unknown, or do nothing and become an old man filled with regrets?
Final thoughts on Parkinson’s disease written by Steven Dotzler

Alpha-synuclein is a protein that is abundant in the brain and its dysfunction is known to be a key player in the pathway that leads to the neuro-degenerative disease of Parkinson’s. This protein becomes a problem in the neurons of the brain and can lead to Parkinson’s when it is either created with improper structure due to a mistake in the DNA or the protein’s is altered once it is created from the DNA sequence by another intracellular compound.  Alpha-synuclein, as the name implies, is normally in the form of an alpha helix which is essentially a long thin strand of twisting amino acids put together in a similar fashion to the classic image of DNA we all think of.  If the DNA sequence that codes for the alpha-synuclein protein is even slightly out of order you can get a mutation that causes the protein to take a completely different shape known as the beta-sheet.  This shape of a protein is very different than an alpha-helix, as the name implies it is when the amino acids of the protein come together in a sheet like formation, similar to a piece of paper.  In the case of Parkinson’s this becomes a problem because in this beta sheet formation the proteins are able pack closely together, like a ream of paper, and create these protein aggregates that cause the neurological problems that we see in Parkinson’s.  Another way that the alpha-synuclein protein could be modified to be formed in beta sheets instead of an alpha-helix would be through direct modification by another cellular component.  One type of compound that could cause this would be peroxynitrite, which is an oxidizing compound, meaning that an oxygen type of molecule will react chemically with another compound and change it usually for the worse.  This is why we here so many things about food products with antioxidants being so good, because the idea is that they will prevent this oxidation of important components of your cells.  Back to the protein, if the protein is oxidized and the structure of it changes it too can also end up in a beta-sheet formation which like I have previously mentioned would lead to the aggregation of these proteins into large masses that eventually become Lewy Bodies and cause a lot of problems in the neurons of the brain.

In neurochemistry we recently discussed an article written about concussion and traumatic brain injury.  This is a very relevant topic and I’m sure we have all heard much about it in recent news, especially in regards to the best sport on the face of the planet, football.   Reports of previous NFL players coming out with confessions of repeated concussions and the terrible side effects that developed out of them have spurred officials to take drastic measures in concussion treatment and prevention.  As seen in the video link that is embedded, the NFL and its players are by and large positively receptive to the changes taking place within the NFL.
Video: http://www.vikings.com/media-vault/videos/Vikings-Helping-To-Raise-Concussion-Awareness/e94acbfd-0d6c-4b54-8dea-811b53a6c480
The video mentioned ways of testing for concussion on the sideline.  What our article talked about was the neuroscience behind concussions.  Things like blood-brain barrier shearing, axonal retraction balls, and widespread neuronal depolarization are products of the physical injury caused by the biophysical acceleration of a concussive injury.
What makes me sad about concussion is that although it is a serious issue and does need to be watched carefully, many parents forbid their children from playing based on the risks of concussion.  Concussions can be devastating, especially if there is a repeat injury before the body can heal the initial damage. However, individual concussions are not nearly as damaging as chronic repetitive concussions as long as adequate time is given for recovery. Meaning, in short, that if adequate measures are taken children and teenagers should be allowed and encouraged to play sports.

For generations our parents have been telling us to “just walk it off” or “rub some dirt in it”.  However, recent studies have suggested that this may not be the best motto to go by for people today. With many competitive sports injuries and situations related to those injuries occurring, research is being conducted to explore what those injuries could mean for people in the future. The latest data has shown that concussions and brain injuries athletes in football and boxing have obtained have many of the same characteristics of Alzheimer’s Disease and other neurodegenerative diseases. In fact some of the same genetics that make people prone to developing Alzheimer’s Disease has been shown to increase the damage done and recovery time for the brain in athletes with similar genetics.
What does this mean for athletes in the future? Will more athletes need to be genetically tested to continue to play? As of right now, high school, college, and professional level sports have regulations in place for athletes when a concussion or other injuries occur. However, many times people overlook concussions or players feel so much pressure that they attempt to hide their injury in order to continue playing or get back to playing sooner.  This competitiveness to play down injury, such as a concussion, could be the reason that many athletes continue to suffer mentally and emotionally after they are done playing a sport. However, is this not what we have been taught from a young age, to stop being a “baby” and get back into the game? Yet, the brain is such a delicate part of our bodies that needs time to heal. The complication in brain injury is it is less noticeable. You do not see swelling, bruising, or lacerations, like you do in other injuries. This makes brain injuries harder to detect and diagnose.
Yet, how does a concussion occur? A concussion can occur from a force hitting the body so hard as to cause the brain to slam into the walls of bones that make up the skull. As a result people have many cognitive signs and symptoms that show the physical damage the brain has undergone. Victims begin having troubles focusing, as well as performing academically, and have troubles with short-term memory retention. Repeated injuries can eventually cause the membrane that protects the brain, the blood brain barrier, to loose its protective ability. These injuries also cause the cell membranes of neurons to allow the transport of particles, ions, and so forth across without regulation. The crossing of these particles results in overexcitation of the neurons of the brain, increased risk of further brain damage, and sometimes neuronal death.  As the neurons become compromised by the injuries sustained, similar characteristics found in neurodegenerative diseases, such as plaque build up and neuronal degeneration begin to appear.
Does this threat than have enough of an influence to change the way we play contact sports such as boxing or even eliminate them? At what point does enough become enough and we need to realize our limitations? These are many of the questions that athletic committees have to address and inform athletes of when deciding on rules and regulations for games. In fact the World Medical Association (WMA) suggested banning the sport of boxing altogether.
If we are increasing our risks of brain disease by participating in a sport, is that worth the pain and suffering it could potentially cause in the future? Do we simply continue to teach coaches, players, and family to understand the signs and symptoms of concussions and brain injury, while informing them of the consequences of not allowing the brain to fully heal? As our sports become more competitive and physical only time can tell what will happen to our athletes. Yet, we should look into the effects before it is too late. With so many health organizations pointing out the effects of such sport injuries, it becomes the responsibility of the athlete, as well as their family and coaching staff to become informed of the risk factors involved with each successive brain injury and determine the risk and benefit of continuing on.
 
 
Resources:
Blennow, K.; Hardy, J.; Zetterberg, H. The Neuropathology and Neurobiology of Traumatic Brain Injury. Elsevier Inc. Cell Press, 2012 Vol. 76, pp. 886-900.