Back to the Future: a look at Parkinson's Disease

When I think about Parkinson’s Disease, the first thing that comes to my mind is Back to the Future. Weird, I know–but Michael J. Fox is one of the most visible people with Parkinson’s and a huge advocate for the cause. This past week we investigated an article regarding PD called Targeting dysregulation of brain iron homeostasis in Parkinson’s disease by iron chelators. Not only reading this article, but all of the research that went along with understanding it, gave me a far greater understanding of Parkinson’s Disease and it’s pathology.

As the article’s title suggests, there is a connection between PD and iron. This was new information for me, and struck me as quite interesting. Iron levels in a person with Parkinson’s differ quite a lot compared to someone without Parkinson’s. Those with Parkinson’s have much higher levels of iron. In addition to iron levels, PD staples include loss of dopaminergic neurons, the aggregation of -synuclein to create lewy bodies, and neurofibrillary tangles.

I thought the article was really awesome because it added to the current research being done on Parkinson’s, but the thing I found most interesting was the parts about iron homeostasis in the brain. I was responsible for researching the mechanism for regulating iron in cells and found some pretty awesome stuff. Iron is bound in the cell by two different receptors: IRP1 and IRP2. The IRPs serve as a dual mechanism in which iron can be regulated. A quick and dirty explanation is as follows: if iron levels are adequate in the cell, it is sequestered and stored for later use; if iron level are too low, the IRP binds to ferritin (this binding inhibits iron sequestering), that way there is more iron available inside the cell. Iron has many properties, one of which is it’s ability to oxidize/reduce molecules in the cell. If the regulation of iron is out of whack, then the oxidation/reduction within the cell will cause problems. This brings us back to -synuclein aggregation and lewy bodies, which are caused by oxidative stress. In other words, this new-found information about Parkinson’s helps explain the things that were already known about the disease. Nifty!

So the question remains: what do we do about all of this iron dysregulation? The answer is in the title of the paper, iron chelators. Iron-chelators bind iron in the cell and help reduce the high levels in individuals with Parkinson’s. This remedy to iron dysregulation is a great option because it will reduce oxidative stress on the cells and lower the amount of -synuclein aggregation and lewy bodies.

This article was really informative and made new connections in the big picture of Parkinson’s research. I think it’s safe to say that next time someone brings up Parkinson’s Disease I won’t immediately think of Back to the Future.

Concussion: More than just a bump on the head

This weeks topic was concussions, which turned out to be really cool and applicable to a lot of people in the class. Before this week I really was not sure what a concussion entailed, having never had one before, all I knew was that it involved getting hit in the head. It turns out there’s more to it than just that…who knew?!

A concussion, aside from being painful, is a very complex reaction to force exerted on the head. This force causes an initial mechanical trauma causes a whole cascade of things to happen, ultimately leading to a flux of ions through many channels in the brain. This rapid depolarization to the brain has many consequences and can lead to permanent damage if not cared for and healed properly. Effects can be memory impairment, behavior changes, headache, inability to concentrate, and in severe cases permanent brain injury. What is worse than one concussion is repeated concussions, especially if the first one hasn’t had time to heal properly. This is seen a lot in high contact sports such as football and boxing. Repeated concussion can lead to long term damage and CTE (Chronic traumatic encephalopathy), which is large-scale neuronal degradation and tau protein build up.

The topic of concussions is one that is actually really applicable to people in our class, as concussions tend to be common in younger people, especially athletes. As we learned in class, a concussion is a time consuming injury, and can be extremely detrimental to physical, and mental function for about four weeks after the fact. Being that proper care for concussion is extremely minimal physical and mental stress, it can be hard to cope with as as a student. This was one of the main points we talked about during our weekly discussion. How should students (whether they be elementary, middle school, high school, or college) go about dealing with a concussion as well as keeping up with classes, and if the concussion was sports related, whether or not to continue with that sport. This topic brought about a lot of good discussion and perspective from students, teachers, and athletes alike. As a group we determined that it would be nearly impossible to keep up with college coursework if you got a concussion, because let’s be real, four weeks of no class isn’t exactly ideal. We came up with the semi-solution of perhaps being able to continue taking classes as independent studies and finish at your own pace. This is a great idea, but would take a lot of logistical work to be able to be implemented.

Green with envy

Flick the lighter. Burn. Inhale. Ahh…that’s the good stuff.

It appears that this routine is becoming more and more common in the daily lives of many Americans. Medical marijuana is on the rise, and multiple states have now legalized it. A lot of people criticize this new trend, while many others are green with envy of the availability of medical marijuana. Why such a discrepancy in opinion? When most people think of weed, the only thing that comes to mind is burnt out hippies and junkies. Weed has a bad rap, and carries a stigma with it. But why?

        This week’s article, Endogenous cannabinoids revisited: A biochemistry perspective, introduced us to a pretty fascinating system within the body. The endocannabinoid signaling system is a family of receptors in the brain that bind the endogenous cannabinoids, 2-AG and AEA, that our body makes naturally. These endocannabinoids (eCBs) play a role in pain relief, appetite stimulation, and motor control. It also just so happens that these eCBs are extremely similar to THC, the active ingredient in marijuana (incredulous gasp!). This means that there are actually specialized receptors in our brains that are made to bind things like THC. This brings me back to the above question: Why does medical marijuana get such a bad rap? Ignorance, mainly.

        It has been supported by scientific studies, like the paper we read this week, that THC as a cannibanoid binds the eCB receptors in the brain and has beneficial therapeutic effects. So why not make medical marijuana legal everywhere? One of the biggest arguments against the use of medical marijuana is it’s addictive qualities. Now yes, marijuana might be addictive, but what isn’t? It isn’t any more addictive that the pain meds that people take everyday. It seems silly to me that people would rather keep using chemically synthesized pills that have who knows what side effects, over this natural alternative. One of the coolest things about medical marijuana (besides the pain relief, and other awesome benefits) is that there are essentially no negative side effects (with proper use of course).

        I think that steps need to be taken towards universal legalization of medical marijuana. The biggest thing that needs to be done is raising awareness of the benefits. People opposed most likely don’t know that medical marijuana actually does have positive effects on the user. Maybe if everyone knew that THC is basically the same as the endocannabinoids already found in the body they would be less opposed to using it as a therapeutic drug. This would be a huge step in medicine, and would help countless individuals suffering from chronic pain, eating disorders and many other diseases.

Dopa what?

Typical conversation before reading the proceeding blog post:

Average Joe: “What’s dopamine?”

Neurochem student: “Well, it’s one of the most common neurotransmitters in the human brain.”

Joe: “Isn’t that some drug that athletes use?”

N.S. : “Not exactly, that’s just called “doping,” and isn’t actually related to dopamine.”

Joe: “Dopamine..like, cocaine, right?”

N.S. : “No, no, Dopamine itself isn’t an illegal drug. It does, however, play a role in drug addiction.”

Joe: “So basically Breaking Bad then..yeah?”

N.S. : …….Oy vey

So what exactly is dopamine, you ask? This is a relatively new area of study for me, but I’ll do my best to get across the important stuff…without putting you to sleep. Let’s start with the basics: first and foremost, dopamine is a neurotransmitter. That is, a chemical compound in the brain that sends a signal from one neuron to another. Neurotransmitters are key players in neural pathways and are essential for executing all of our basic actions and functions. This week in class we looked at a more specific facet of dopamine: the Akt/GSK-3 pathway. I know what you’re thinking, probably something along the lines of “Ak-wha? I’m over this blog.” Don’t let it scare you! The Akt/GSK pathway is actually really nifty and is prevalent in many common neurological disorders. The bare bones explanation of the pathway is as follows:

1. Dopamine binds to the D2 receptor

2. Binding causes the -arrestin complex to form

3. arr deactivates Akt

4. Deactivated Akt allows GSK to remain active

5. GSK gets to do all sorts of fun things in the cell!

Now you’re probably thinking “Why should I care about any of this?” The simple answer is that, whether you realize it or not, your life is filled with topics revolving around this pathway. This is the mechanism of many antipsychotics, is directly related with the treatment of bipolar disorder, and plays a huge role in addiction and substance abuse. Pretty neat, right? While learning about the nitty gritty details of the dopamine pathway or the Akt/GSK cascade may not be as entertaining as watching the latest episode of Breaking Bad, it is far more relevant to our everyday lives. Don’t worry if you don’t understand everything about it–I don’t either!

Living with ALS

 

I was not very familiar with ALS before this week. I had an idea of what it was, but I was not aware of how a person got it, or what was done after they were diagnosed. That being said, I feel that I have learned a lot this past week. I was informed that it is hard to determine when someone has ALS, and when a person in diagnosed, there is very little that can be done to help. There are a few medicines that help prolong the disease, and I also found that by having a larger fat reserve, people with ALS live longer. However, people who are diagnosed with this awful disease will live a very difficult life that will end too quickly.

Not only does this disease take over the individual’s life, but it also requires help from others. Many patients depend on their families or care givers to help them with simple tasks, and hopefully they have a strong support system to help the patient feel as comfortable as possible while facing this devastating illness. I believe that an individual’s attitude towards life, whether he/she is sick or healthy, depends on the people that surround them; this is true for ALS patients as well. The main thing that can really be done for ALS patients is to make their life as comfortable as possible. It would be the hardest thing in the world to watch someone I love lose a battle with a disease after fighting so hard, but I would do everything in my power to help.
There are still a lot of questions I have about this disease like: how can we improve the lives of these patient and make their time on this earth better? There is so much unknown about the brain and why things happen the ways they do, and how can we fix one problem without creating another one? Scientists in this field have a lot of work ahead of them, but I feel we are headed in some sort of direction; whether or not it is the right one will be discovered soon enough, but for now I am thankful that there is research being done to understand the basics of many diseases that have ruined the lives of many.

A Glass of Milk A Day Keeps ALS Away?

Amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig’s Disease, is a rapidly progressing neurodegenerative disorder. The symptoms of the disease usually start between 40-60 years of age. Initial symptoms include mild muscle weakness, cramps, muscle spasms, or muscle stiffness. Although the symptoms are often overlooked at first, symptoms progress until a patient is no longer able to care for himself, eat unassisted, or breathe unassisted. The symptoms of ALS can be attributed to loss of motor neurons; however, like many neurodegenerative disorders, the cause of the degeneration of motor neurons is still unclear.
One possible cause of motor neuron loss is protein misfolding and cellular response to misfolded proteins. The article “Calcium-dependent protein folding in amyotrophic lateral sclerosis,” suggests that changes in the normal calcium levels or signaling causes stress in the cell, which causes the cell to not function properly. The first issue is protein folding. Basically, the cell requires proteins for transport, structure, enzymes to assist reactions in the cell and many other functions. Not only must the building blocks (amino acids) be strung in the right order, but the proteins must also be folded into the correct three-dimensional structure in order for it to function properly. This is where the endoplasmic reticulum (ER) comes into play. When proteins are made, they travel through the ER and are folded along the way. Chaperone proteins, found in the ER, are responsible for folding other proteins into the right shapes. Ca2+ levels in the ER regulate the chaperone proteins’ activity.
When calcium levels in ER deviate from homeostasis, the cell attempts to continue folding proteins correctly. One way to do this is to activate the unfolded protein response (UPR). The UPR tags a protein to tell the ER not to allow the protein to leave until it is properly folded. Without the proper UPR, the cell will experience ER stress for accumulation of proteins, which ultimately results in cell death. Both ER stress and UPR are thought be implicated in ALS pathogenesis. Further research is needed to develop treatments that target the ER and UPR to improve ALS symptoms and survival time. Currently, the average survival time for ALS patients is 3-5 years. By better understanding the progression of this disease, advances could be made in treatment to slow the progression or even cure ALS. Investigating calcium and calcium-dependent folding proteins appears to be a promising direction for ALS research.

The Capstone Experience

There is a heavy emphasis on liberal learning at Concorida College. Even as a chemistry major, I have taken courses in art, history, sociology, & other areas of study that are much different than what I’m used to in chemistry. Overall, I feel this has been a very positive experience for me. One of the hallmarks of Concorida’s liberal arts education is the capstone course that most students take either their junior or senior year.

As a senior, I chose to take a capstone in my major, and that course turned out to be neurochemistry.  Prior to taking neurochemistry, I had little to no neuroscience experience. This was frightening as well as exciting. I was worried I would just be lost in the content due to jumping into an upper level class with no prior experience, but I was also excited at the idea that I could get some insight on a whole new field of chemistry.
To be honest, the learning curve was steep. I had no idea what what going on for the first month or so. But after that, things started to click. I started to make connections just like any other class I’ve taken and since then I’ve grown to enjoy it. The most intriguing part of this class was how we brought the topics we were dealing with in class to a broader, more universally applicable level, instead of just focusing on what happens in a textbook or in a lab. The class essentially looked at a review article focusing on one neurological topic (usually a neurological-related disease/condition), worked as a class to understand the topic, and then discussed the relevant issues pertaining to the topic. We talked a lot about how the topic applied to society and how it will affect future generations. We talked about the politics, beliefs, and habits of our society and how they pertained to the topic. It was unlike any other science class I had taken before, and I really enjoyed it .
The bottom line is that most classes I have taken are lecture based and, for the most part, are pretty contained to themselves. The topics are discussed in a very limited scope and there usually isn’t a drive to take the information we have learned outside of the classroom or lab. With my capstone class, I was almost doing the exact opposite. We figured out how things were working as a class and then looked at how we could bring that information out into the non-scientific community. As a scientist, I know this is what I’m eventually going to have to do from time to time, and this class has been a huge benefit in showing me how to do that. I think it’s important for any subject to be able to communicate it’s issues to other areas of study, and science is no exception. Overall, I feel my capstone experience demonstrated the goals of a liberal education, and I am glad I took the course.

My Capstone Experience

This semester I took my capstone course in chemistry – neurochemistry. This course was unlike any other chemistry course I have enrolled in. It was not the normal class where you sit, take notes, listen to a lecture and then have an exam covering the material. Instead, this course required much more individual involvement and research. Each week a topic was covered and current research was read on the subject. Most of the time, these articles were very overwhelming to read and our understanding after reading the article was very limited for the first day of class each week. The next day in class, each person had a topic that they covered individually and they told the class what they found out about the topic through their individual research. The third day of class each week we had a discussion day, and discussed what we still did not understand about the topic covered or what we thought was particularly interesting. These discussion days were my favorite days – we simply talked about what we had learned in the last week of classes and connected it to other knowledge we already knew. Having very little neurochemistry background when I enrolled in the course, I can say that I have learned a lot about neurotransmitter signaling and how this signaling can relate to diseases. The amount of knowledge I have gained within the last couple of months has far surpassed my expectations. I have learned so much about various diseases and how they can relate to so many different things in the body. I do believe that my speaking skills have greatly improved this semester also. Every week we had to present to the class a topic that we researched on our own. At the beginning of the semester, these were the days that I dreaded. I used to dread the days when I had to stand in front of my peers and speak. I would get so nervous and shaky, I would rush through my presentation and forget to say half of the things I had learned about my topic. By the end of the semester, I was much more comfortable standing up in front of others and sharing what knowledge I had acquired through my individual research. Overall, this capstone experience has been a great one. I have enjoyed this class very much and have improved my speaking skills, my ability to research, and my ability to summarize things and make them easy to understand for others.

ALS – A Sad Disease

Our final topic of the year is ALS – a disease that when diagnosed with, will be fatal within 3-5 years. There are very few medications for the treatment of this disease, only one has been approved by the FDA in 1995. The cause of this disease is not yet found, but the latest research seems to believe that ALS is linked to abnormal calcium levels in the cell. These abnormal calcium levels in cells are believed to cause misfolding of proteins and stress on the endoplasmic reticulum (ER) of cells. Because the ER is a site for protein packaging and folding, when the ER is under stress, the mechanisms that are normally used to repair these misfolded proteins begin to malfunction. These malfunctions lead to accumulations of misfolded proteins in the cell and eventual diseases, such as ALS. This disease is a very sad disease. Symptoms of ALS are first muscle spasms, and eventually when so many motor neurons are lost, paralysis. People that develop ALS can take medications to help them feel better, or the one drug that is approved for the treatment of ALS. However, the one drug approved for treatment causes heavy liver damage, and cannot be taken for extended periods of time. This drug does not stop the disease from happening, but it does slow the progression. Once a person is diagnosed with ALS, it seems that they are faced with eventual death. ALS is a fatal disease that moves quickly, killing a person in approximately 3-5 years. Research needs to be done to further understand the mechanisms in which this disease affects the body so that further treatments can be developed as well as an eventual cure.

Alzheimer's Disease: the good, the bad, and The Big Mac

Alzheimer’s disease (AD) is a neurodegenerative disease that has been increasingly making its way to the forefront of devastating diseases in our society. It’s likely that many of us know someone who is affected by AD, yet the exact mechanisms are not well understood and there is no current effective cure. Alzheimer’s disease exhibits severe dementia as a result of the degradation of neurons and synapses in the brain. AD is a disease that not only harshly affects those who have the disease, but also those who are left to care for and look after those who have it.

The causes of AD are not entirely known. There are countless pathways that are thought to contribute to the eventual build up of amyloid plaques and neurofibrillary tangles. The amyloid plaques build ups of the beta amyloid protein and the tangles result from the build up of a wrongly phosphorylated tau protein. Pictured above is a comparison of a healthy human brain and a brain of an individual with severe AD. It is easy to see the damage done to neurons as a result of AD, and one can probably imagine the consequences of such neuronal damage.
So what do we do about this? Shouldn’t science was supposed to have an answer to these problems. Do we all just wait around our whole lives and hope that we don’t get Alzheimer’s and essentially lose our minds? It turns out that there are certain things we can do to help prevent it. In particular, our diets might be a good place to start.
To say that eating your vegetables will protect you from getting AD later in life would be a bit of a stretch. However, there are some significant ties between those who have unhealthy diets and those who develop Alzheimer’s.  A primary result of consistently eating unhealthy food is obesity, which has been on the upshot as of late. In turn, many obese people develop insulin resistance and type-2 diabetes. This has a whole set of consequences in itself, but there have been distinct connections made between those who are insulin resistant and those who develop AD.
Could our diets really have an effect on our health to the extent of Alzheimer’s disease? I feel like we could all admit that we could eat a little better. Sometimes it’s just easier to grab McDonalds on the way home or eat a bag of chips in the car. Our society has a very “go-go-go” attitude about everything, including food. It’s also difficult to see the long term affects that eating a bag of Doritos every other day has on us until it’s basically too late. Personally, I would love to eat healthier food. However, I’m broke college student. When I go to the store it’s much easier to buy a frozen pizza than some organic sugar peas. I think it’s primarily a problem of our society, and our diets seem to play a much larger role in our overall health than we probably realize.

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