I have always viewed Parkinson’s disease as something that only effected a person’s movements. After this week, I have learned that it effects to much more than that. There are many differences in the brain from a person who has Parkinson’s disease, and a person who does not.
Parkinson’s disease is characterized mainly by the loss of dopaminergic neurons, and the formation of Lewy bodies that reside in the remaining dopaminergic neurons. These Lewy bodies replace other elements within cells. Lewy bodies are not the only disruption in cells that a person with Parkinson’s disease has; there are also neurofibrillary tangles (NFTs) present within PD patients. NFTs and Lewy bodies are very representative of PD patients, but it was interesting to learn that the amount of iron in people with PD is significantly higher than people who do not have PD.
This raised an interesting question: does the food a person eats play into the likelihood he or she will develop PD? As a class, there have been many topics that relate neurological disease to the food that is put into our body. The relation with type 2 diabetes and Alzheimer’s disease, as well as green tea being extremely beneficial to PD patients in helping reduce oxidative stress, thus increasing the amount of properly working biological functions, has shown that what we feed ourselves may have a drastic effect on our brain’s health.
Although it should be no surprise, it is still fascinating that what we eat really does determine how healthy we are, both physically and mentally. Food and water are the resource for most of the functions our body conducts. As time has gone forward, we have discovered that food is an important factor in our livelihood, but it takes a lot of effort to eat what our body truly needs, as well as being able to afford it. With this dilemma, companies have capitalized by selling pills, tablets, etc. to keep a person at optimal health without having to worry about what else is being put into his or her body.
This relates back to Parkinson’s disease in that those with PD have a much higher concentration of iron than those who do not have PD; is this due to an individual’s diet? There have been many studies conducted showing the benefits of a Mediterranean diet or an Oriental diet (a real Oriental diet, not one consisting of deep fried chicken smeared in some sugary sauce—it is delicious, but not very comparable to what is actually eaten in the Orient) compared to a typical diet of those who live in the United States.
The amount of red meat a person in the United States is extraordinary. This could result in a high concentration of iron in the brain, thus being an influence on developing Parkinson’s disease. It is probably not going to fix the problem entirely if people change the way they eat, but it could be beneficial, just as drinking green tea has been shown to do.
"Light it up and Take a Puff, Pass it to me Now"
For years marijuana has been used both medicinallly as well as recriationally. These days society has made a huge commotion about this drug, trying to determine if it is an “okay” thing to allow people to use. There is plenty of evidence to suggest that this drug is being used more and more frequently whether it is legal or not. For instance a lot of artists, espcially in the rap and hip hop industry, have used references to marijuana use in their songs. These songs are being listened to everyday by millions of people. Often times the main listeners of this music are impressionable young children or young adults. This makes me wonder what kind of impact this is having on the youth of America in whether or not they are using marijuana. Not only that but why are people using the product; is it because getting high is cool and fun, or could it actually help these younger people feel more calm, get more sleep, eat better, etc.? I think this is why it is such a hot topic and why some states have decided to legalize this drug where others say it is too dangerious or unhealthy to allow.
Since the use of marijuana in the United States is such a controversial issue, have you ever found yourself asking why? or what makes a plant, of all things, something to argue over? If you have, you may want to first understand what makes this plant a drug. Endocannabinoids were the topic our neurochemistry class discussed this week by reading and anylizing the article “Endogenous cannabinoids revisited: A biochemistry perspective”. We discovered that the plant Cannabis sativa (marijuana) contains more than 400 chemical components, 60 of which belong to the cannabinoid class. Recently the main cannabinoid psychoactive component in marijuana was discovered. This is what we know as THC. THC does produce many psyhoactive effects in ones brain. Research has found that these cannibinoids act on the CB-1 and CB-2 receptors in our brain causing a person to feel “high”. Although this is largely frowned upon, recent research has been focussing on how the chemical components in marijuana may be more beneficial than harmful if used properly. For example we discussed that one study found that a certain strain of the drug, that had lower THC levels, can be used to treat people with epilepsy. The reason that a strain like this works better than other strains is becuse there is a cannibinoid called cannibidol in marijuana that is linked with health benefits and is less psychoactive than the THC. By consuming a strain that has less THC and more cannibidol in it, a perosn would have reduced psychoactive effects and possibly have more health benefits from the drug. There is a lot of research going on today that is trying to find out how using cannibinoids in different treatments would work and how they would be beneficial to society. Treatments for a lot of things are blossoming such as: treating cancer and cancer symptoms, helping with eating disorders, slowing down the effects and controlling the symptoms of HIV and AIDS, helping with depression, reducing headaches, and aiding in many pain disorders. I think people warm up to this idea because it is a “natural” solution to very difficult problems we face in the health problems we are experienceing today. A lot more research needs to be conducted in order to pinpoint specific treatments using endocannibinoids, cannibinoid receptors, etc. however, I do think scientists are going in the right direction to discover how marijuana can be considered a treatment not just a drug.
The significance of the Atk-GSK3 pathway
Of the countless neurotransmitters associated with the human central nervous system, dopamine is perhaps one of the most crucial neurotransmitters to understand in its pathways and signaling. Dopamine is utilized in a variety of different regions of the central nervous system, including cognition, locomotion, and emotional behaviors.
The regulation of dopamine is crucial to the well being of human health. As soon as the pathways that govern dopamine signaling, uptake, and various other aspects of its existence in the central nervous system start to get out of whack, things can start heading downhill pretty quickly.
Given the complexity and variability of dopamine pathways and signaling, it is absolutely miraculous that dopamine-related disorders aren’t more common. There are many different signaling pathways that each contain different chemical interactions that illicit responses. Specifically, the Atk-GSK3 pathway is of great importance. Disruptions in this pathway have been linked to the development of disorders such as schizophrenia, bi-polar disorder, depression, Parkinson’s disease, and many others.
In the grand scheme of things, chemical reactions occurring at the molecular level seem minuscule compared to the implications that arise from a disease like Parkinson’s or schizophrenia. However, if we wish to treat these disorders to the best of our ability, we need to focus on the underlying mechanisms that produce the effects we see. Completely understanding these pathways will hopefully allow us to treat these disorders in the most optimal way and possibly even provide methods of curing diseases that have previously been incurable. Research continues to uncover more and more information about dopamine and other important neurotransmitters, and it is crucial that we keep funding and supporting this type of research.
As natural as it get
We recently read an article about endocannabinoids. Yes, cannabinoids just like the active ingredient in marijuana, THC, or tetrahydrocannabinol. The part of the article that was most intriguing to me was the fact that these chemicals are completely natural in our body, as in we make them. Endocannabinoids act like a relay system in our body. Our neurotransmitters are released and bind post-synaptic neurons, which releases endocannabinoids. This tells the pre-synaptic neuron to stop releasing neurotransmitters. THC has a similar effect on the body. Here is where our discussions got interesting. THC acts exactly like a chemical our body already produces but has a huge stigma around it. Because of this stigma, one of the potentially beneficial parts of marijuana, cannabidiol, is often forgotten about. Cannabidiol is another cannabinoid, so it acts like the ones our body produces and THC. However, cannabidiol is far less psychoactive than THC. Cannabidiol is the part of marijuana that is often linked with the positive effects, such as preventing tumors and stopping seizures. In fact, a fairly recent article on CNN talked about how a specific strain of marijuana that was high in cannabidiol and low in THC was used to treat a girl with Davet’s Syndrome, a severe version of epilepsy. So we have natural endocannabiniods and cannabidiol that are generally helpful, but THC is the most commonly heard of and causes a lot of stigma for all cannabiniods. I wonder were the stigma came from in the first place. It does make you think, we have these chemicals are body uses for regulation that are also found in a plant. Some people use the plant to get high, others use it for health benefits. Should we be utilizing this plant, even though it is illegal now? Who knows, but cannabinoids are an interesting chemical nonetheless.
Akt, Gsk, Dopamine and how they can fix your brain
The other week in class we discussed the Akt/Gsk pathway and Dopamine receptors. To put it lightly the article we read was dense. Through all the scientific language and technical terms one general idea stood out. Your body releases dopamine, dopamine binds these receptors, and the receptors keep Akt inactive so Gsk can remain active and cause cellular responses. As exciting as that all sounds what does it matter? Well dopamine is one of the most important neurotransmitters in the brain and these proteins play a major role in its signaling pathway. Research is currently investigating the role of these signaling proteins in psychological disorders such as Bipolar and Schizophrenia. The antipsychotics we use now are effective but come with harsh side-effects. This is because these pharmaceuticals typically block dopamine receptors and while this works to stop the psychological problems, it causes a widespread effect on the body. The hope is that the issue with psychological disorders is that maybe the problem lies farther downstream from the dopamine receptor in the Akt/Gsk pathway. If we can find a protein or something that is causing the problem and can find a way to fix it we can hopefully manage psychological disorders without affecting something as major as dopamine receptors. This is easier said than done. The kind of research it takes to find what protein is causing the issue and figuring out a way to fix it costs huge amounts of money and takes a lot of time. But, nonetheless, the important of the Akt/Gsk pathway in the body cannot be undervalued. Some day it may lead to a better antipsychotic drug, or just a better understanding of dopamine.
Should we puff puff pass on the use of cannabinoids?
Despite its legal status, the use of marijuana is not uncommon. In fact, it is the most commonly used illegal drug in our society. In addition to its recreational use, marijuana has been used medically for hundreds of years. Although the use of marijuana might not be new, finding out how it works has just begun. This week in neurochem we discussed the article “Endogenous cannabinoids revisited: A biochemistry perspective.” As we discussed the intricacies of marijuana, THC, endocannabinoids and their receptors, it became apparent that THC and its natural analogues may be more beneficial than they are harmful.
The first step to understanding the benefits that cannabinoids can have comes through understanding how they work. The cannabinoid receptors were first discovered when researchers started looking into how THC and marijuana work in the body. They discovered certain receptors on cell membranes that specifically bind THC. As research continued, scientists discovered molecules that are naturally produced in your body that also bind these receptors. The most common of these molecules are known as 2-AG and AEA. The receptors are known as the CB-1 and CB-2 receptors. As research continues, more endogenous cannabinoids have been suggested as well as at least one more receptor type.
So what are the benefits that can be caused by cannabinoids? Medical marijuana has been used for Cancer, HIV/AIDS, multiple sclerosis, anorexia, anxiety, depression, and numerous other illnesses and conditions. In addition, it has been shown to have anti-proliferative and analgesic effects. In addition to the use of medical marijuana, researchers have been studying analogues of THC, the primary active compound found in marijuana. One of the most promising compounds is known as cannabidiol. Cannabidiol is second only to THC in the marijuana plant in terms of presence. It has been shown to have less psychoactive effects and may have more medical benefits than THC. Currently, a large amount of research is focused on cannabidiol in order to better understand how it works and the benefits it may have.
With the noted benefits of cannabinoids, the question then arises of how we should approach this knowledge. Although the use of marijuana is largely prohibited, its use may be beneficial in the treatment of a variety of neurodegenerative diseases. In addition, cannabinoids seem to alleviate a wide variety of problems without the side-effects of many pharmaceuticals. Cannabinoids might just be the answer to improvement of treatment for a variety of diseases; the knowledge we do have points to the positive effects that cannabinoids can have. So should we just take this knowledge and run with it? Although I can see and understand the benefits that cannabinoids can have, I think it is important that more research is done prior to widespread use. In addition, if marijuana or other cannabinoids are used for treatment, it is important that they are properly monitored by a physician as with any other medication. With proper research and monitoring, cannabinoids seem to be a promising treatment for a variety of disorders and diseases.
Iron: More than a Metal
Parkinson’s disease (PD) is a disease in which dopamanergic neurons experience substantial damage and even death. It affects 1-2% of people overage the age of 60, affecting more men than women. The causes of PD have typically been associated with oxidative stress and other toxic actions which lead to the build up of Lewy bodies in the brain which lead to death of neurons. A new study entitled, Targeting dysregulation of brain iron homeostasis in Parkinson’s disease by iron chelators, discusses the effect that iron might play in PD. One of the interesting things about this article is that it is able to supplement theories that are already in place about PD with a new idea. It doesn’t discount any of the old information about PD, but it adds a new piece to the puzzle that could help solve the problem.
Brain-iron homeostasis is regulated by interaction between two types of cells in the brain called endothelial cells and astrocytes. It is also regulated by two proteins called IPR1 and IPR2. These proteins help to regulate the amount of each type of iron in the brain. In the body, iron can take on two forms: one with a charge of +2 and one with a charge of +3. It is important to keep these two types of iron regulated because dysregulation of these two ions has been visible in PD. Too much iron in the brain has been studied and been shown to lead to PD, Alzheimer’s disease, and Multiple Sclerosis. Iron is important for the brain because it used to either reduce or oxidize molecules. Improper oxidation or reduction can lead to problems.
Like mentioned before, dysregulation of iron +2 and iron +3 has been seen in the brains of PD patients. One specific problem this causes in PD is the aggregation of alpha-synucleuin proteins due to iron radical molecules in the brain to form Lewy bodies. These Lewy bodies lead to death of neurons. One way this paper talked about treating the iron dysregulation is with iron chelators. Iron chelators are molecules which bind to iron and then remove it from the body. Iron chelators are therapeutic because they have antioxidant effects, prevent alpha-synucleuin aggregation, and can stabilize HIF (a molecule that is used to regulate transcription).
PD might not be as “hot” of a topic in terms of neurological disorders compared to others, but it still important to try to understand where it comes from and how it can be prevented and treated. Some people may feel disconnected from PD since it affects only a small part of the population. Further research into the mechanisms of PD could also bring about conclusions about other neurological disorders as well.
Since PD is diagnosed later in life, I think it may people don’t think much about preventing it. But, in my opinion, prevention is the best way to deal wit disease since it possibly alleviates having to treat the disease in the future. With the iron part of the PD story, it can be difficult since many women struggle with anemia. When trying to eat an iron-rich diet to control anemia, it would be unfortunate to develop PD as a consequence.
For people without anemia, in order to prevent PD it seems it would be important to eat a sufficient amount of iron to stay healthy, but keep the excess amount as low as possible.
The article also spoke about the positive effects of green tea in terms of PD. If this fact were made more public, it could be possible to help prevent/treat PD with the simple treatment of drinking or supplementation of green tea.
Type 2 Diabetes, a Precursor to Alzheimer’s Disease
Many people are aware of the connection between insulin resistance and type 2 diabetes. New research presented in the article, Possible Implications of insulin resistance and glucose metabolism in Alzheimer’s disease pathogenesis presents a link between insulin resistance, diabetes, and Alzheimer’s disease. When most people think of insulin, they think of blood glucose levels. This is a great association because insulin is a hormone released into the body which tells the body to absorb glucose when its levels are high, for example right after a meal. Before reading this article, I was unaware that insulin played any role in the brain. Recent studies have shown that insulin is produced in the brain and can have intense effects in the central nervous system. A specific receptor, IGF-1, was found in the brain that responds to insulin and can help regulate important neurological functions such as: energy homeostasis, survival of neurons, longevity, and learning/memory.
Alzheimer’s disease is a condition characterized by neurological degradation and memory loss. Just like insulin resistance is they “key word” to diabetes, accumulation of amyloid-Beta plaques in the brain is the “key word” to Alzheimer’s disease. Amyloid-Beta (AB) plaques form in the brain from the aggregation from AB proteins which are formed from the processing of amyloid precursor proteins (APP). APPs are found in membranes of the brain, but their natural function is still unknown. When they are cut with specific enzymes, AB proteins are formed. Abnormal folding of these proteins leads to their aggregation, which leads to brain deterioration and Alzheimer’s disease. AB plaques in the brain lead to a high level of inflammation in the brain which also contributes to the negative symptoms of Alzheimer’s disease.
The connection between diabetes and Alzheimer’s disease may not seem obvious, but one important link between the two is inflammation. Brain inflammation plays a large role in Alzheimer’s disease and is key in its pathology. The connection between insulin and Alzheimer’s is made because in the periphery, insulin plays an important role in inflammatory responses. Low does of insulin have been shown to have anti-inflammatory effects but high levels of insulin may increase inflammation and also activate oxidative stress (another factor in Alzheimer’s disease).
In summary, Alzheimer’s disease is associated with AB plaques, inflammation, and oxidative stress. Diabetes is associated with insulin resistance. Insulin in the brain is associated with regulation of inflammation. When these three concepts are connected, it leads to scary realities for the American public.
Type 2 diabetes is quickly infiltrating the American public at a younger and younger age. People of all ages are developing diabetes. If diabetes is a precursor to Alzheimer’s disease, and people are getting diabetes at younger age, this could lead to the onset of age of Alzheimer’s disease being lowered. This could be a huge problem for society. Many people with Alzheimer’s experience such severe memory loss that they cannot even recognize their own family members. Most people with Alzheimer’s disease are at an age where they are retired, have grown children, and are able to live in a facility that is able to accommodate their needs. But if people are to be diagnosed with Alzheimer’s at 50 years old because they contracted diabetes at a young age, the disease would be more taxing on their life. Most 50 year old people still have job and still have dependent children. Having a disease which so severely impacts memory would not make it easy to hold down a stable job or raise children. Alzheimer’s disease doesn’t necessarily quickly end a person’s life. Living with Alzheimer’s disease for 25 plus years would be extremely difficult for both the individual and their family.
Now that this research has come up, it is more than ever necessary to change the habits of the American public. Prevention of diabetes is even more important now that it is clear that prevention, or at least delay, of diabetes can prevent, or at least prolong, Alzheimer’s disease. One main way the American public should react to this article is with a change in diet. Unhealthy, sugary foods should be minimized in the American diet and foods high in antioxidants should replace them. Nutrition is an important factor in the development of type 2 diabetes. Increased nutritional values in the diets of Americans have been shown to help prevent type 2 diabetes. American health care occasionally struggles with preventative health care, but it is integral that people realize what kinds of negative problems can occur due to poor nutrition: type 2 diabetes, which recently has been identified as a precursor to Alzheimer’s disease.
You Want Me To Do Drink What…?
The focus of this week’s neurochemistry discussion was Parkinson’s disease. Parkinson’s disease is a progressive neurodegenerative disease that affects movement. Common symptoms of Parkinson’s disease include tremor, bradykinesia (slow movement), stiff limbs, and poor coordination and balance. Like many other neurodegenerative diseases, the cause of Parkinson’s disease is unknown and currently there is no known cure. However, it is known that patients with Parkinson’s disease experience cell death in an area of the brain known as the substantia nigra, which has high levels of a neurotransmitter (chemical signaling molecule) known as dopamine. Dopamine is the neurotransmitter used to regulate and coordinate movement in the body.
Recent research has shown that dysregulation of iron levels in the brain may play a role in the development of Parkinson’s disease (PD) as well as other neurodegenerative disorders. Iron levels have been found to be increased in the substantia nigra in Parkinson’s patients, which has led researchers to believe that regulation of this molecule is linked to PD. Iron is an important molecule in a number of biological processes such as DNA synthesis, cellular transport, storage and activation. A number of proteins are needed to maintain a consistent level of iron in the blood. Iron-regulatory proteins (IRP) and iron-responsive elements (IREs) are in charge of controlling the creation of proteins that regulate the amount of iron allowed in the blood and how much iron is taken into cells. When iron levels increase (not solely due to age) to the point that regulatory proteins are not able to handle the increased concentration, accumulation of iron can have disastrous effects. First, iron reacts with hydrogen peroxide and produces radicals, which cause oxidative stress. Oxidative stress in cells ultimately causes cell death. In other cases, iron causes proteins to accumulate in the cell. One of the hallmarks of Parkinson’s disease is the formation of Lewy bodies, which result from the accumulation of the protein of a-synuclein. Iron accumulation has been shown to contribute to two signs of Parkinson’s disease.
Now knowing that iron accumulation poses a serious threat, what can be done to lower levels of iron? One mechanism of decreasing the adverse effects is through chelation, or binding of iron ions to prevent iron from acting in cells. M30, a synthetic drug that is able to reach the brain, is showing promise in reducing iron levels in the brain and protecting dopaminergic neurons. However, M30 is not the only therapeutic option available for Parkinson’s patients. Surprisingly, there is a simple, natural way that everyone can reduce his or her levels of iron. (-)-epigallocatechin 3-galate (ECCG), an extract of green tea, has been found prevent neuron death in the substania nigra by binding to iron ions. Green tea is readily available and a natural therapy option that may reduce the harmful effects associated with excess iron. Green tea as a therapy option gives patients hope and motivation because they are capable of influencing their risk for Parkinson’s disease through accumulation of iron. Iron dysregulation offers a new, potential target for therapy. Further research is needed to continue looking for a cure for Parkinson’s disease.
Type 3 diabetes
Obesity is on the rise in the United States and with this comes a number of health issues. One of those issues is Alzheimer’s disease (AD). Obesity can lead to diabetes which is the body’s inability to regulate glucose. Insulin plays a vital role in the brain as shown in figure 1. It stops oxidative stress, one of the leading causes of aging, and apoptosis (cell death). In diabetes the insulin no longer bind to insulin receptors correctly. This causes the cell to perform acts otherwise not performed if working properly. In short, insulin isn’t able to bind to receptors causing things called neurofibrillary tangles. These tangles cause neurological death in the brain which causes AD. Because of this, many call AD type III diabetes, because of its link with insulin. This is just another reason why it is important to stay healthy and to fix the obesity problem in the country.
