Legalizing marijuana has been a hot topic in media recently. In class last week we talked about the way that marijuana affects the body and the different chemical pathways that are important in these processes. The pathways in total are called the endocannabanoid pathways. We learned that this pathway is incredibly complicated and is not well known.
What we do know, however, is that THC is the active ingredient in marijuana. THC can do many great things in the body. It often is neuroprotective, it can act as an anti-inflammatory, and it can cause apoptosis (cell death) in cancer cells. These are great things! However, THC also has psychoactive effects. This begs the question, are there alternatives to THC that can be as effective as THC in the body without having the psychoactive side effects? The answer is yes! There is a medicine that was recently approved by the FDA to mimic the actions of THC and it is without the psychoactive side effects found in THC. Have you heard of this great option though? My guess is probably not because of…
It seems that the legalization of medical marijuana has been such a big deal because some individuals just want to get high. When we have legitimate medicinal options such as cannabidiol, with the only difference being that there are no psychoactive effects, what benefit would legalizing medicinal marijuana actually give patients? If certain individuals wanted to smoke marijuana, they should just say so. We are seeing states legalize and consider legalizing recreational marijuana and that is a whole different discussion. Recreational marijuana can be a great source of tax revenue for a state, but if these individuals that are pushing for this hide behind medical marijuana then it can tarnish the movement for medical marijuana. Just think of it this way, when you first heard of medical marijuana, what did mental image formed right away? And so I say: if you want to party with Mary Jane, just say so.
Marijuana Isn’t Just for Getting High
Marijuana has been an extremely hot topic in today’s society. From states one-by-one legalizing medical marijuana to the straight up legalization of the drug for recreational use, it is something that we hear about on a normal basis. You can argue that marijuana is entirely bad and should be illegal, but the science of pot disagrees. It does have its benefits, in particular treatment of certain medical conditions.
The plant Cannabis, from which marijuana is derived, contains the active ingredient tetrahydrocannabinol (THC) which is what causes the effects of the drug. It is psychoactive and can cause relaxation, anxiety, “the munchies,” and other effects. THC is a member of the cannabinoid family, meaning that it activates a certain family of receptors in the brain. However, our own body produces substances that are very similar to THC – endocannabinoids. These endocannabinoids have many of the same effects of marijuana, minus the psychoactive part. This similarity is why marijuana can be so beneficial medically.
First, a little on how endocannabinoids work in our body. Endocannabinoids activate two main types of receptors in the central nervous system (the brain and spinal cord): the CB1 and CB2 receptors. When endocannabinoids bind to these receptors, they can affect memory, cognition, appetite, and sensation of pain, among other things. Two different substances do most of the binding to the CB1 and CB2 receptors. Anandamide (AEA) was the first endocannabinoid discovered and effects not only the nervous system, but also the immune and digestive systems. 2-arachidonoylglycerol (2-AG) is very similar to AEA but is made and broken down differently and is also found in higher concentration in the brain than AEA.
Both AEA and 2-AG have huge effects on cell survival. When an endocannabinoid binds to its receptor, it activates a number of different pathways. Some of these pathways can trigger cell death, while others can stimulate cell survival. Both of these effects can be important medically. For example, cancer is an overproduction of certain cells, and endocannabinoids can help regulate that overproduction and cause some of those cells to die. This is a good thing, as it reduces the size of the cancerous growth. In contrast, endocannabinoids can also help prevent against excitotoxicity in the brain, which can prevent the death of neurons. This is important for neurodegenerative diseases like ALS, Parkinson’s, and Alzheimer’s. A great deal of research needs to be done to help determine when or why endocannabinoids sometimes cause cell death and sometimes promote cell survival, but the information we currently have is a good start.
So what does this have to do with the legalization of marijuana? Because marijuana and THC have the same effect on the CB1 and CB2 receptors as AEA and 2-AG, it can be used to treat some of the medical conditions listed above. Other effects of cannabinoids include increased appetite and decrease intraocular pressure, which is why marijuana can also be used to treat anorexia and glaucoma, respectively. Marijuana, however, is not the perfect drug. Due to the psychoactive effects of THC, using it for medical purposes can also have some unwanted side effects. Current research is working on creating synthetic marijuana-like drugs that do not have the psychoactive problem, like cannabidiol for example. For the meantime, though, don’t automatically assume that because marijuana has been illegal in the past that the legalization of it – medicinally or recreationally – is necessarily a bad thing.
Relax, Grandma. It's just a little weed.
Marijuana has shown ever increasing promise as a treatment for cancer, dementia, epilepsy, glaucoma, obesity, diabetes… the list goes on and on. Scientists are currently searching for a synthetic alternative to the active ingredient in marijuana, THC, that will produce the same responses without all the hassle of any of the psychoactive negative side effects, such as hallucinations and paranoia. But while researchers hunt for their miracle drug, the general public isn’t quite so convinced. Though states such as Colorado have legalized the recreational use of marijuana, a national resistance to marijuana legalization still remains.
For the first time ever, a 2013 Gallup poll shows that a majority of Americans now favor legalizing marijuana, but just barely (http://www.gallup.com/poll/165539/first-time-americans-favor-legalizing-marijuana.aspx). While the young adults of today’s society are all for cannabis use, the senior citizens of our society don’t quite agree. After designating the plant as an illegal drug for the past century, perhaps the stigma of the term “marijuana” proves to be just too much. Despite the stigma, medicinal marijuana could be a great alternative to the grim chemotherapy and radiation treatments we put our loved ones through to fight their cancer. Or an actual treatment for the Dementia that steals our grandparents, parents, friends, and family away.
Although we have yet to find the perfect drug blend that provides the benefits of marijuana without all the side effects, scientists are well are on their way. Researchers have discovered cannabidiol, another active ingredient in marijuana that produces many of the positive effects, without most of the negative side effects. And while we don’t quite understand all the pathways and receptors involved in our bodily system that THC or cannabidiol acts on, the most recent research is quite promising, as we make our way toward learning exactly how marijuana causes hallucinations, appetite stimulation, and cancer cell death, among other effects within our bodies. In addition, researchers are looking for other variants of THC and cannabidiol that may stimulate specific beneficial responses such as bone growth to fight osteoporosis, relieve muscle spasms for patients with MS, and eliminate inflammation for those with Crohn’s Disease.
So, before you write off legalizing medical marijuana, I encourage you to learn more about what the most recent research says and be open to its potential. Let’s not forget about the analogous drug morphine, the socially acceptable and commonly used pain killer, which is in fact just a variant of heroine. With more research and studies on marijuana we may be able to discover new, safer treatments and maybe even cures for even the most horrendous diseases. Don’t let the stigma marijuana carries prevent you from understanding the great healing benefits we might be able to unlock from the iconic seven-leafed plant.
Cannabis: More Than Meets the Eye
Marijuana is a type of cannabinoid which has had a long-held reputation for recreational drug use throughout the world. The main plant source, Cannabis sativa, has been cultivated for generations because of its psychotropic effects. In the last two decades, it has emerged as a legal form of drug treatment for patients with cancer, Tourette syndrome, eating disorders, and many other medical issues. The use of marijuana as a therapeutic tool continues to be a social and political issue. Twenty states have approved the use of medical marijuana since 1996. Colorado has implemented the most recent marijuana legislature, by legalizing recreational as well as medical usage. Other states may be soon to follow pending the economic and social outcomes.
With all this hype around the topic, what do we really know about its effects? I know I am guilty of minimalizing marijuana usage solely as a means to get high. In the article this week, I learned that there is much more to the drug. The key to marijuana’s medical usage lies in its dominant chemical component, Δ9-tetrahydrocannabinol (THC). Its discovery has directed research towards finding cannabis derivatives which have the same positive results within the body without the unwanted psychological effects.
Humans have a built-in system that is acted upon by cannabinoids, such as marijuana, as well as cannabinoid-like compounds native to the body, called endocannabinoids. The most common endocannabinoids include anandamide (AEA) and 2-arachidonylglycerol (2-AG). The discovery of naturally occurring compounds similar to cannabinoids that act upon the same receptors was the first major step to discovering its potential usage. The endocannabinoids act on receptors, called CB1 receptors, that are localized in areas of the brain which control memory, cognition, movement, and pain reception.
Both AEA and 2-AG induce the same physiological effects as marijuana such as numbing of pain, motor depression, and a trance-like state. The endocannabinoids play a role in a number of different systems within the body including the central nervous system, immune, endocrine, gastrointestinal, reproductive, and more. This highlights the biochemical importance of the endogenous cannabinoids and the potential for cannabinoids such as marijuana for drug treatments for a broad range of diseases.
On a cellular level, the endocannabinoid system is vital for balancing cell production and cell death depending on the factors that interact. By controlling the rate of cell growth and death, the endocannabinoid system may play a vital role in regulating different types of cancers, such as breast carcinoma and prostate. One method of activation is through the adenylyl cylase and ERK activation. Another mechanism induces superxoide anion formation and caspase-3 formation, a key protein in many pathways that lead to cell death. A third pathway involving CB2 activation involves increased levels of ceramide, a lipid, that induces mitochondrial stress. In the end, the cell is destroyed which is important when regulating harmful cancer cells.
A lot of people attribute marijuana use to teenage misuse. We forget about the cancer patient who is using it to induce their appetite during chemotherapy treatments. Or the person with multiple sclerosis who uses it to stop muscle spasms. I believe that there are health-related benefits to the drug, but they are yet to be refined. This review covered just a few of the areas that could really benefit from developing effective cannabinoid-like drugs. The debate over legalizing one drug overshadows the benefits that its derivatives may have in controlling the same disorders without the psychological effects. It is important to take a step back from our previous conceptions and look at the possible positive uses of marijuana and other cannabinoids, because there is still a lot more to the story.
Sources used:
http://www.whitehouse.gov/ondcp/state-laws-related-to-marijuana
http://www.sciencedirect.com/science/article/pii/S1098882313000087
Cannabis: Reaching a New “High”
Cannabis: Reaching a New “High”
We humans have a close relationship with the kingdom of plants. Produce graces our table each night at dinner with a cornucopia of colors and flavors. Age-old oaks stand tall in their glory providing shade over our parks and dropping leaves for our children to pile. And who can forget the marvelous flowers that fill the air with delicious scents? But there is a plant the strikes controversy in the general public. Some give it praise for its effects while others shun it for the same reason. This plant is cannabis.
Cannabis is notoriously associated with the production of marijuana, a drug that causes a slew of physical and psychoactive effects. But it is not the whole cannabis plant that causes these effects. Within the plant is a chemical called Δ9-tetrahydrocannabinol which is much more commonly known as THC. THC is the active ingredient in marijuana that is responsible for the variety of effects on the body. So how exactly does this happen?
When THC is ingested, it travels through the cells of the body searching for two specific proteins that will receive the THC with warm welcome. These proteins are called CB1 and CB2 and are specialized types of proteins called receptors. While many proteins in the body are used to process the nutrients we eat or to stimulate growth of our muscles, these receptors are used as our body’s communication network.
Imagine that you have just received a text message from your spouse that reads “Can you stop and pick up milk on your way home from work?” Assuming that you don’t reply “I’m pretty busy, can you do it instead?” this text would signal a response from you that would cause you to stop at the grocery store and coincidentally purchase a gallon of milk. This same situation can be applied to how THC affects the CB1 and CB2 receptors. Think of THC as the text message that signals you, acting as the CB1/CB2 receptor, to respond. After receiving the message, you then work to accomplish the task that was asked of you.
Ok, perhaps radio waves from cell phone towers are slightly different that chemical signaling between the cells of the body, but you get the point. Anyway, these CB1 receptors are found throughout your body, but happen to be concentrated in the brain while CB2 receptors tend to localize in the immune system. When THC locates and binds to these receptors, it triggers them to inhibit another protein called adenylyl cyclase. Adenylyl cyclase may be hard to pronounce, but it is central in activating and stopping many responses carried out by the body. You can think of adenylyl cyclase as a sort of “headquarters” that receives the signals from many receptors and coordinates the variety of chemical signals it receives and translates them into physical actions, or in the case of marijuana, the well-known list of physical and psychological changes in the body such as appetite, pain and pleasure, memory, and mood.
But why are these receptors found in our body in the first place? Were they placed in us simply because God wanted us to experience the effects of cannabis? Of course not! The human body is very efficient, and the CB1 and CB2 receptors do in fact have a normal purpose that does not include marijuana. Normally, these receptors are stimulated by two chemicals called anandamide (AEA) and 2-arachidonoylglycerol (2-AG) that the body produces naturally. These two molecules are called endocannabinoids (endo = in, cannabinoid = cannabis-like, i.e.- cannabis-like chemicals produced in the body) are the intended targets of the CB1/CB2 receptors. Although these two molecules do not cause the same psychotropic effects found in THC, they still regulate many of the same body functions such as appetite, cardiovascular activity, sensation of pain, and even bone mass!
So then, how can we use this information for the advancement of modern medicine? Interestingly, researchers are looking into developing pharmaceuticals that are similar to THC, but that do not cause the psychotropic effects that complicate prescribing them to the general public. So far, a drug called cannabidiol is emerging as a likely contender for this job. Already we know that these drugs can stimulate appetite and can be used for the treatment of glaucoma or pain, but new findings suggest that they might also be useful in the treatment of cancer as well.
I don’t want to bore you to death with in depth explanations about each of these, but the moral of the story is that it is very likely that we will see advances in the treatment of many medical conditions by using the information gained from studying these cannabis-like molecules.
It all started with a little plant called cannabis. And when we just so happened to set it on fire, we discovered that there were some effects! It was this creativity that sparked a revolutionary movement to learn more about the human body, unearthing a new class of useful medications and functions in the process. Cannabis certainly is a controversial little plant in popular culture, but its usefulness will likely help us to achieve the next pinnacle in medicine, or perhaps appropriately put, a new high.
Final thoughts on Endocannabinoids written by Steven Dotzler
Marijuana the Miracle Drug?
It seems that every day a new state is legalizing marijuana, or a new study is coming out praising the medical benefits of marijuana. For those of you against the legalization of marijuana for medical purposes, I’m sad to say but it has been shown time and time again to be therapeutically useful. Now you may ask; how is that something we have been told for years is along the same lines as other recreational drugs that are supposed to ruin your life actually do something beneficial for you?
First things first let’s clear the air about the use of marijuana for medicinal purposes. The benefits of marijuana are due to the active chemical compound in marijuana known as THC (tetrahydrocannabinol). The reason THC can have therapeutic benefits is because it is in the class of chemicals known as cannabinoids and your body actually naturally produces its own cannabinoids for every day functioning of your cells, these are referred to as endocannabinoids. Endocannabinoids are naturally occurring cannabinoids found within (endo-) your body. The major functions of these endocannabinoids that are being targeted for the use of marijuana as a medical therapy are their ability to induce cell death and even protect cells from death. You are likely wondering; how on earth something can both protect cells from death but also induce cell death, this is because the receptors that endocannabinoids bind to are found all throughout your body on different types of cells and control a variety of cell functions. So, depending on the type of cell, as well as the type of receptor stimulated, cannabinoids can cause cell death as well as protect cells from death. This ability of cannabinoids to induce cell death is being looked at for a potential cancer treatment because some cancer cells, such as breast cancer cells, have been shown to react to the presence of extra cannabinoids though cell death. The ability of cannabinoids to protect cells is being looked at in medicine as a potential method of treatment for many neurodegenerative diseases such as Alzheimer’s and AL S because some of the causes of these diseases involve pathways that are activated by cannabinoid receptors of brain and nervous system cells, so if excess cannabinoids can protect these cells from being damaged, they could potentially be used to slow the progression of the disease or even prevent it.
Alright so this sounds great right? Marijuana kills cancer cells and protects cells being damaged by other diseases, it’s the perfect drug…..Not quite although cannabinoids have been shown to have some to these positive effects it, like any other drug, has its negative side effects. Along with its ability to cause death to cancer cells it also targets your immune cells and can cause death to them as well. As we all know as well marijuana has psychoactive effects on the brain such as paranoia and anxiety which are also negative side effects. So sadly, no marijuana is not a miracle drug and is not anywhere close to it, but some of its properties show signs of potentially useful medical treatments. There is a chemical compound that is supposed to have all of the benefits of cannabinoids without any of the “high” or other psychoactive side effects called cannabidiol. This drug is yet to be approved by the FDA or go through significant clinical trials but it has shown promise in early research. For more information on cannabidiol visit http://www.projectcbd.org/.
In the end a lot still has to be learned about cannabinoids and their benefits in medicine before they become a mainstream form of treatment.
ALS: Caring on Ice
Why should people care about ALS. It is a disease that affects a relatively small amount of the world population. People should care because it is a brutal disease. ALS hits hard and it kills. People should care about ALS like they should care about any other disease, empathy. We should care because it makes other people suffer.
The ice bucket challenge has done a great job of spreading the name of ALS. Everyone knows that the ice bucket challenge is raising awareness towards ALS. But that is about all that it does. I knew that the ice bucket challenge was about ALS but I had no idea what ALS was, who was effected by it, and what could be done to treat it. After taking this course, reading our article, and discussing ALS in class my understanding of the disease has grown immensely. Something needs to be done than just get the name ALS out there. What ALS is and what it does to people needs to get out into the world and become common knowledge.
An interesting yet sad truth about ALS is that we are not exactly sure what causes it. We know that ALS leads to motor neuron death and we know that there are many players that might cause this. This is where research into ALS can be very exciting and very daunting at the same time. There are many paths to choose from and who knows which one will lead to better treatment. One thing is for sure however the more we know about ALS the more likely we will be able to create a more effective treatment for this terrible disease.
ALS, More than a Social Media Phenomenon
By now, we have all either seen, been nominated, or actively participated in the ALS ice bucket challenge. We know that the money is going to a good cause, either to fund ALS research or help those who are affected by this awful disease. We know influential people who have had the disease such as Steven Hawking and Lou Gehrig. But how much do we know about the disease itself? Lets break it down into more bite sized pieces.
Description:
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by muscle weakness due to the breakdown and death of motor neurons (the cells that deliver signals from the brain to the muscles). This leads to loss of neuronal function and ultimately to paralysis. (Additional information can be found at the ALS website, www.alsa.org)
Cause:
The primary cause of necrosis (death) of the motor neurons is a phenomenon called excitotoxicity. Excitotoxicity in ALS, occurs when there is too much of a neurotransmitter called glutamate in the synapse (the junction between two nerve cells). This causes overstimulation of the cell, leading to problems with functional pathways further down the nerve cell. The primary receptor to glutamate that has been studied is called NMDAR. It is different than other receptors for glutamate because it requires co-agonists, or other substances in addition to glutamate, to trigger a response by NMDAR.
Current Treatment:
There is only one drug currently on the market that is used to treat ALS. The drug Riluzole acts by suppressing the release of glutamate and the receptors that respond to glutamate in the synapse. This method attempts to reduce the excitotoxicity that is caused by ALS in the synapse.
New Findings (co-agonists):
(Glycine/D-serine)
Both Glycine and D-serine are co-agonists which affect the NMDAR receptor. Glycine has been shown to promote the release of glutamate which can increase the risk of excitotoxicity in a neuron affected by ALS. On the other hand, high levels of D-serine have been linked with NMDA toxicity. This occurs because the over activation of NMDA causes a pathway that leads to cell death (ERK1/2-/p38)
(Zinc)
Zinc performs several important functions within the cell. A vast majority of zinc found in the body is tightly bound to zinc dependent enzymes. Missense mutations within these zinc dependent enzymes have been linked to 20-25% of ALS cases. It has been found that those zinc deficient enzymes can then lead to ALS.
(Polyamines)
Polyamines, such as spermine and spermidine, have been found to be allosteric modulators of the NMDAR receptor (they bind to the receptor in a site different that the normal active site and by doing so, change the shape and function of the receptor). It has been found that these polyamines enhance the activity of NMDAR, thus causing a pathway which leads to cell death. Unlike many other neurotransmitters, polyamines are found throughout the body and not just in the neurons. In patients with ALS, polyamines have been found in higher concentrations within red blood cells.
It is clear that there is no one cause ALS, and the pathways that lead to its symptoms are very complex and for the most part are not fully understood. Although fund raisers such as the ALS ice bucket challenge might seem trivial, they take steps toward finding an ultimate cure for the disease, and offer the families of those who are affected, with much needed support.
ALS – We Need to Care
I’m sure that in the past few months your news feed has been flooded with the Ice Bucket Challenge. It probably even got to the point where you couldn’t stand seeing it anymore, maybe even resent the whole concept. Why do you care about ALS, it hasn’t affected anyone you know….yet.
You’re probably right. According to the ALS Association, only about 30,000 people have ALS right now – that’s 2 in every 100,000. We all feel the need to support those causes that affect us, or that are mainstream, like Parkinson’s disease, breast cancer, leukemia, and whatever else that comes across the TV or our radio, but why not ALS. ALS doesn’t have that famous spokesperson like Michael J. Fox or Muhammad Ali. It doesn’t have billions of dollars funneled into research, and honestly, how does a bucket of ice help the cause?
I can’t answer those questions, but imagine this. You are completely tied up and your mouth is taped shut. You are in your house and some stranger is taking all your things, one by one. You know what is happening, but there is nothing you can do about it. That is ALS. Sufferers become a prisoner in their own body, fully aware of what is happening, but without the means to do anything about it.
There are so many ways that ALS occurs. The onset is not necessarily genetic, only 5-10% of cases are due to inheritance. Instead, your body mutates on you, changing a gene that then causes the most intense traffic jam of transmitters inside your brain and spinal cord. Research is difficult because once that mutation occurs there are so many different ways that ALS affects you, that stopping just one doesn’t fix the problem. Imagine the worst traffic jam in the largest city. All the cars don’t come from in same direction; they converge into one central location. Opening up one of the pathways does not ease the flow for a different route; in fact it may hinder it. This is what ALS does inside the nervous system, except there is no way to clear the overload.
Pharmaceutical companies have the difficult task of trying to develop drugs to alleviate this problem, only for them there are other problems as well. Our brains are very protected in our body. The ability for drugs to enter our brain is very, very limited. While this is great for a healthy brain, it makes the task virtually impossible for those that are affected. So far there has been one drug that has been able to extend the life for those affected with ALS for a whopping 5 months. Yup, that’s right, less than half a year.
So the next time you see an ICE bucket challenge show up on your news feed, don’t get upset or frustrated. Think of the two in every 100,000 that are trapped inside their own body, fully aware, but unable to let you know. Become the voice for those that don’t have a voice for themselves, and help become part of a cure.
Behind the Bucket: A mechanism behind ALS appears to be too much of a good thing
Before the ALS awareness social media frenzy, the term “ice bucket challenge” meant nothing more to me than the 5+ month reality of living in Minnesota, also known as winter. The ceremonious dumping of ice became a phenomenon of Facebook friends and celebrities alike, but many jumped on the ice bucket bandwagon without much thought to the disease behind it other than a donation. While the challenge spread awareness about ALS, many don’t actually know what happens in the disease. Let’s break the ice and break down ALS, shall we?
ALS stands for amyotrophic lateral sclerosis, an adult-onset neurodegenerative disease characterized by major motor neuron loss in the brain stem, spinal cord, and cerebral cortex. Motor neurons are nerve cells in the brain and spinal cord that send signals out to muscles, telling them when and how to move. As motor neurons degenerate and die in ALS, signals get sent at random, uncoordinated rates, and eventually no message is transmitted at all. When the signals are sent spastically, this causes muscle spasms, also referred to as fasciculations. When the motor neurons die, the muscles no longer receive signals telling them to move and they atrophy, or waste away. Defining characteristics of ALS are muscle weakness, spasms, and atrophy. The muscle atrophy gets progressively worse, and those affected have difficulties swallowing, chewing and speaking and eventually become paralyzed. The body withers away, but someone affected with ALS is painfully aware of losing motor functions and control, and within a few years, losing their life.
How are these messages sent and how does it go so wrong in ALS? Glutamate, a major excitatory neurotransmitter in the brain, is released and helps transmit a message from one motor neuron to another, eventually leading to muscle movement. It binds to two receptors, AMPA and NMDA. Glutamate is an important neurotransmitter that is also involved in many other important functions like learning and memory. When too much glutamate is present, it overexcites neurons and they die, a concept known as excitotoxicity. The article discussed in my Neurochemistry class at Concordia College focused on the role of NMDA receptors.
For many of you, the term “NMDA receptor” may provoke a similar reaction to that of the knights in Monty Python when confronted with the flesh-eating rabbit. Don’t fret; let’s use this castle theme to help explain the role of the NMDA receptor.
Think of a motor neuron as a castle and the NMDA receptor as the gate entrance. Glutamate is like a gatekeeper at the NMDA entrance; it is bound to the door and allows a certain amount of people in. The people represent calcium. As more people enter the castle, they create energy that excites the atmosphere inside the castle, and the excitement spreads. However, if there are too many gatekeepers at the entrance (too much glutamate), it becomes chaotic and they let too many people in the castle. The inside of the castle becomes overcrowded (too much calcium in the cell) and the energy turns from excitement to chaos, causing things to break in the castle. Eventually, the castle (motor neuron) is destroyed. In terms of ALS, massive amounts of motor neurons die in the spinal cord, causing motor deficits and eventually paralysis and death.
Unfortunately, the mechanisms behind motor neuron degeneration in ALS are not as simple as a castle analogy. NMDA is not the only receptor involved, and there are many other contributing factors to the progressive motor neuron loss. However, with more knowledge about receptors like NMDA and their role in the motor neuron death, we can more accurately target the mechanisms for treatment. Current treatments for ALS are limited but target the excessive amounts of glutamate (the gatekeepers in the castle example) in hopes of lowering glutamate levels and slowing the motor neuron degeneration. Though the general public cannot directly find the cure, we can support the cause by becoming educated on diseases like ALS in addition to supporting research funding.
Credits: The article discussed can be found here: http://www.sciencedirect.com/science/article/pii/S0925443912002736
Images used via Google search: ALS image from http://www.bestonlinemd.com/what-is-amyotrophic-lateral-sclerosis-or-als/
Monty Python image from: http://i.imgur.com/hJDbC6o.jpg?3
NMDA receptor image from: http://knowingneurons.com/2013/01/30/ltp-when-neurons-make-a-long-term-commitment/
**”Monty Python and the Holy Grail” is a British comedy and is not associated with ALS or its pathology**
