If we think of research like a giant puzzle, it is easy to get excited when new information is discovered, when a few pieces are connected. But this doesn’t erase the fact that many pieces have yet to be found, whether that is underneath the couch, behind the door, or as with many literal research labs, behind more research.
Several adult and pediatric neuroinflammatory diseases are no exception to this analogy.
Nitric Oxide (NO) is a key neurotransmitter and neuromodulator that plays a role in a wide range of neuronal activity throughout the central nervous system. The particular enzymes that help synthesis nitric oxide within the body have three different subtypes (neuronal nitric oxide substrate (nNOS), endothelial nitric oxide substrate (eNOS), and inducible nitric oxide substrate (iNOS)).
Unfortunately with excessive amounts of nitric oxide in the central nervous system, there can be consequences. With normal amounts of nitric oxide involving nNOS, regulation of synaptic signaling and plasticity between neurons occurs. However, with excessive amounts of NO, this can lead to neuronal toxicity, apoptosis and cell death. eNOS acts as a crucial regulator of cardiovascular homeostasis. When NO is synthesized, regulation of the blood vessels occurs, which maintains an anti-proliferative and anti-apoptotic environment. Unfortunately, as with almost all neurotransmitters and neuromodulators, the right amount is key, as excessive or low amounts can cause permanent damage.
The particular substrate of iNOS has been a valuable topic of interest for its potential role in neuroinflammatory diseases in research. iNOS release of NO has a large involvement in regards to immune responses.
Side note: *It is important to know that the role of glial cells (cells that help protect and provide support to neurons), play a very critical role in the development of the brain.
Now to attempt and connect the puzzle pieces…
In regards to three neuroinflammatory diseases, there may be a link between the function of glial cells and their interaction with nitric oxide.
In Periventricular leukomalacia (PVL), this disease is characterized by white matter premature death, which can lead to cerebral palsy and cognitive deficits in premature infants. According to the article our class read, there may be two possible causes: lack of oxygen or blood flow OR damage to the glial cells. Research has shown that nitric oxide damages developing oligodendrocytes (a type of glial cell).
In Krabbe’s disease, a fatal degenerative and neuroinflammatory disorder, is one that impacts the myelin sheath of the nervous system. Observations in research has shown that psychosine (a type of glycosphingolipid), which accumulates in particular in Krabbe’s disease, “under inflammatory conditions leads to the iNOS-mediated NO overproduction, which in turn may play a role in the pathogenesis of this disease.”
With the relationship between NO and glial cells, it is important to keep in mind the whole picture, instead of focusing on a few pieces (even as crucial as those few pieces may be). Researchers know that the “iNOS overexpression is not the only mechanism by which glial cells can affect neuronal function.” There are obviously more pieces to be discovered, but researchers are hopeful that the understanding of the complexities behind the involvement of NO can be a first step.
Larger than Erections: The effects of NO in neuroinflammatory diseases
Nitric Oxide. A small diatomic molecule consisting of one part nitrogen, one part oxygen. It’s a well known vasodilator and cellular signaling molecule within the body. It is a derivative of common drugs such as nitroglycerin and other blood pressure medication. The compound itself is a gas that quickly dissipates in the body, but while present, is crucial to such processes such as neurotransmission, vasodilation, reducing inflammation, etc.
When the public hears of nitric oxide, they typically think of it in one of two ways: as a supplement used to boost performance in athletes and body builders, and as part of the medication so many men take for their bedroom troubles. Erectile dysfunction is a “disease” that affects roughly 18 million men in the U.S. and is characterized by impotence and the inability to routinely to get erections “when the moment strikes”. The market for virility drugs that treat ED has taken off since the 1970’s and is a $5 billion dollar industry. One can imagine the amount of “little blue pills” that hit the market each year and are taken by men who have a little trouble “getting it up” on occasion. The drug industry has capitalized on the insecurities of men everywhere and hawked their erection medication as crucial for those who even on occasion, can’t sustain or have an erection. There are so many other factors that go into that topic, but that is an article for another day.
The mechanism of action for ED medication involves the increase of NO in the body of the penis, leading it to the increase of cGMP by bind to guanlyate cyclase. This leads to vasodilation/muscle relaxtion, increasing blood flow and leading to erections. Pretty simple right? NO is a crucial part of this drug and works well in leading to “more fulfilling” sex lives for many men, but it is much more important than the body builders and once a month bedroom champions it is known for.
In the brain, NO is a neuromodulator/translator that plays a significant role in chemical signalling and neuronal inflammation. When acting at normal levels, NO provides good things to the body such as vasodilation, modulation of hair growth, and is part of the human immune response when generated by cells within our body. The problems for NO arise when over/under regulation of NO production in the body contributes in negative ways. The increased production can cause an increase in reactive nitrositive species, which are key intermediates in the body, but also contribute to nitrositive stress and apoptosis. Brain inflammation is also a factor of increased NO in the Central Nervous System and plays a big role in brain diseases such multiple sclerosis. The increased NO levels also lead to increased risk for early neuron death.
The purpose of this blog was to enlighten the public on how nitric oxide is much more complex than purely a derivative of erection medication or a muscle supplement. Thank you for reading
Obesity: A Biological Trap
Obesity as a Brain Disorder
Have you ever thought, “If I just had more willpower I could resist all the unhealthy foods I tend to eat”? I’m sure you have heard someone recommend that if you want to become healthy just eat more fruits and vegetables. And I bet you have even heard someone tell another to simply give up something (carbs, desserts, fats, etc.) in order to lose weight. These ideas and suggestions seem true; we do not argue them. More veggies and less dessert will help with weight loss. However, the idea that more will power is the key may not necessarily be correct. In the article I read for my neurochemistry class this week, we learned about obesity as a brain disorder. In the abstract, the first paragraph of the article, the author refers to over nutrition as a biological trap independent of the initial trigger. To me, this connotation has serious implications toward how obesity is treated and perceived.
“Biological Trap” Studies in Rats
As a simple and comprehendible model, studies with rats, has offered good insight into habituated choices of diet. Some results of such studies include:
- Early exposure to fatty food predisposes the animals to favor a high fat diet
- Animals fed with a high fat diet became insulin and leptin resistant and had high blood pressure
- Prenatal and postnatal exposure of the mother to a high fat diet increased the offspring’s weight gain and influenced their dietary habits
- Continuous access to food high in fat leads to more weight gain
These results are significant, even when relating it to humans, because the rat is a very simple model. The results contain no influence from cognition (as they would in humans) or cultural and social influences. The simplicity allows us to see the basic ideas at work in the human body without the confusion of human consciousness. These are the risk factors and conditions, along with some consequences of being predisposed into falling into the biological trap that is obesity.
Activity in the Obese Brain
To explain further what perpetuates the cycle of over nutrition and the biological trap, I want to discuss the brain activity of an obese individual in comparison to a healthy weight individual. Obese individuals have a greater response to the presence of food. Obese individuals have a higher enhancement of anticipated reward compared with lean individuals. Furthermore, the obese brain has less dopamine receptors making the feeling of fullness and pleasure much less after eating a meal than in lean individuals. This is shown in the image below. The obese brain has lighter colored pleasure centers, showing less dopamine receptors and reward activity after a meal.
Willpower Might Not Be Enough
To hammer home the idea that obesity is a brain disorder and not a lack of will power I will direct you to the next image below that I took directly from the article I read.
I am not posting the image because I hope to explain every detail of the science behind obesity. I wanted to share the image because I think that it shows just how complex obesity is. Many other symptoms that go along with obesity do not receive enough attention. They include depression, memory, and learning deficits. Furthermore, this image shows the web of connections that make up the disorder. Each component should be taken into consideration, especially when one feels as if obesity is a moral, cultural, or personal issue. While these components do have influence in the disorder, the key to treating and preventing obesity in America, a country saturated with unhealthy and fatty foods, is understanding the brain science behind the disorder. This will lessen the negative connotation and perception of obesity while helping narrow and focus treatment toward each individual.
Glial cells and their role in development of neurological diseases
Types of glial cells and their role in the nervous system:
Glial cells include, astrocytes, microglia, oligodendrocytes, and schwann cells. The nervous system is built from neurons and glial cells. Gila cells’ functions include providing support for the brain, assisting in nervous system repair and maintenance, assisting in the development of the nervous system, and providing metabolic functions for neurons.
Glial cells and production of NO:
Activation of glial cells in response to trauma, ischemia, and inflammatory damage express iNOS enzyme, which synthesizes nitric oxide (NO). This is a bioactive free radical, which acts as meuromodulator and neurotransmitter in the brain. Although NO performs these important roles in the brain, over production of it by the glial cells induces harmful effects on neuronal function. High concentration of NO has role in neurologic disease such as stroke, neurodegenerative disease, demyelination and neuroinflammatory disease. https://moodle.cord.edu/pluginfile.php/468418/mod_resource/content/1/glial%20nitric%20oxide%20in%20neuroinflammation%20like%20ALS.pdf
Overproduction of NO:
The result of high concentration of NO leads to production of toxic derivatives of NO, which alter the function of mitochondria and other proteins in the brain. NO increases the permeability of blood-brain barrier (BBB) in MS patients. This causes further inflammation and demyelination of the brain cells (neurons). Demyelination means destruction of the protective sheath that cover axons of the neurons. Ultimately, all these lead to loss, destruction of the brain.
Glial NO and neuroinflammatory diseases in children:
- Krabbe disease
- Periventricular leukomalacia (PVL)
- X-linked adrenoleukodystrophy (ALD)
Is it worth it to research and try to treat neurological diseases occurring with againg?
One of the topics that we discussed was the importance of various research have been going on to understand and find treatment for neurological diseases; Are these diseases part of aging and there should not be such research about them done? Everyone in our group had different ideas about this question. In my opinion, what we gain from various research is to understand the disease and as a result learn more about the physiology of the brain. No matter how old one’s loved one becomes, that person still needs to be taken care of in any possible way. Aging is a process, which everyone is facing. By progress of science about disease associated with aging, people can enjoy their lives as they become older.
Oh NO! Nitric Oxide and Neurodegenerative Disorders
Nitric Oxide is a free radical produced by glial cells in the brain as an immune response to infection. It falls into the category of reactive nitrogen species that is often paired with reactive oxygen species. Together these make up RONS (reactive oxygen and nitrogen species). Almost all of these molecules are produced in response to infection and cellular damage. They are highly reactive and can cause cellular damage on their own. Their main function would be to attack the bacteria or whatever is causing the damage to the cells by reversibly binding to their proteins and other molecules, but they also are produced in smaller amounts as a byproduct of metabolic processes.
Normally, these molecules are broken down readily by certain enzymes such as SOD, catalase, and NO synthase after they have done their job so as to prevent them from doing any damage to their own cells. These primary RONS are necessary for normal function within the cell, and may even contribute to certain signalling pathways.
However, in neurodegenerative disorders, there is an excessive amount of RONS. This can be caused by many things, such as the enzymes that break down RONS not functioning correctly, the processes and signals that create RONS being overactive, or overactive microglia and excess inflammation. What happens when there is a lot of RONS, is that they start to react with each other. For example, nitric oxide can react with superoxide to produce peroxynitrite.
Peroxynitrite is one of several secondary RONS that are very bad. These secondary RONS are not as easily broken down by those molecules that break down the primary RONS, and they have no other particular enzymes of their own. This means that they last much longer in the body, and can wreak havoc. Plus, they are even more reactive. Peroxynitrite can bind to amino acids, nitrating them and causing them to lose their function. It can also oxidize molecules that have a transition metal in them such as hemoglobin, myoglobin, and cytochrome c. This changes the transition state of the metal and renders the molecule nonfunctional. This is obviously very bad, and leads to cell damage and death.
As we age, we normally accrue higher amounts of reactive species. In fact this may be one of the main contributors to the breakdown of cells that occurs with normal aging. In neurodegenerative disorders this occurs rapidly in particular neurons, causing a lot of damage and neuronal loss. Anti-oxidants and anti-nitrosatives found in fruits and veggies like blueberries and spinach can help by breaking down some of these reactive species, but more research into finding out more about how we can prevent this process from occurring is definitely warranted.
Parkinson's Disease – What's going on?
Parkinson’s Disease (PD) is a neurodegenerative disorder affecting dopaminergic neurons in a specific part of the brain called the substantia nigra. This normally manifests itself as a series of motor impairments that begins with a slight tremor and gradually results in the inability to walk and take care of oneself properly.
In PD, a particular protein inside the dopaminergic neurons becomes misfolded; alpha-synuclein. The misfolded alpha-synuclein can aggregate with itself and muck things up. When a lot of alpha-synuclein comes together, it develops into what is called a Lewy Body. These Lewy bodies are large clumps of non-functional aggregated protein that they get in the way of normal cellular functions and induce apoptosis, which is cell death. This cell death is one of the major contributors to the loss of the dopaminergic neurons found in Parkinson’s Disease. But what causes the proteins to misfold in the first place?
The answer is inflammation and oxidative stress. Oxidative stress is caused by free radicals that are formed in the endoplasmic reticulum and mitochondria. This happens normally with age, but in PD it occurs early specifically in the dopaminergic neurons. Certain toxins can induce some of this to occur, and there are genetic predispositions as well. Free radicals are very reactive molecules that can irreversibly bind with proteins and other molecules in the cell. If this occurs in the endoplasmic reticulum, it starts to not function properly and creates misfolded proteins like alpha-synuclein. This can also happen in the mitochondria, which causes it to also not function properly. Mitochondria are essential for cellular function, and this by itself can lead to cell death are PD symptoms.
Glial cells near these dying neurons try to help put by initiating an inflammatory response, such as releasing pro-inflammatory cytokines. Normally, this helps by attacking whatever is causing things to go wrong. However, in this case, this inflammation leads to the production of more free radicals and furthering the damage.
To even further the progression of the disease, it appears that misfolded alpha-synuclein can act as a seed that can be transferred from an affected neuron to a healthy neuron, causing the healthy neuron to start producing misfolded alpha-synuclein as well.
To date, most treatments for PD solely work on the symptoms, usually by adding more dopamine to counteract the loss of those dopaminergic neurons. There is no cure. However, the information scientists have gathered has led to a much further understanding of this debilitating disease. Parkinson’s is a multifactorial disease that involves oxidative stress, inflammation, protein misfolding, and mitochondrial malfunction. There is no one drug that is going to cure Parkinson’s, but just maybe we can find the right combination of treatments to erase the damage that is being done.
The Reality of Antioxidants
Oxygen is important for your body’s health, however overexposure to oxygen causes oxidation. Oxidation involves the loss of electrons through a chemical reaction resulting in free radicals. Free radicals start chain reactions within the cell that can cause damage or death to the cell. Oxidative stress can be caused by excess nitric oxide in the cell. At normal levels, nitric oxide is an important physiological signaling molecule, however in excess, nitric oxides displays neurotoxicity. Oxidative stress is thought to play an important role in many neurological disorders such as Alzheimer’s and Parkinson’s Disease.
An antioxidant is a molecule that inhibits the oxidation of other molecules within the body. They are used to stabilize free radicals; keeping them from causing damage to other cells. Antioxidants can protect against and sometimes reverse the damage caused by oxidation. Antioxidants are natural or man-made substances found in many foods or dietary supplements. Examples of antioxidants include:
- Vitamin A found in milk, butter, and eggs.
- Vitamin C found in most fruits and vegetables such as oranges and broccoli.
- Vitamin E found in nuts, seeds, oils and leafy greens, including almonds, kale, and soybean oil.
- Beta-carotene is found in colorful fruits such as cantaloupe and squash as well as leafy greens.
- Lycopene is found in pink and red fruits such as watermelon and tomatoes
- Lutein is found in leafy greens.
- Selenium can be found in cereals, nuts, legumes, animal products, bread and pasta.
The best way to get antioxidants is to eat a healthy diet of vegetables, fruits, whole grains, and nuts. Consuming a variety of the above foods is important to establishing healthy levels of each antioxidant type. Although multi-vitamin supplements provide a good balance of nutrients, too many nutrients from supplements rather than food can be harmful.
The science behind the role of oxidative stress in aging and neurodegenerative disorders and the use of nutritional antioxidants as treatment is complex. Antioxidants have not been shown to have strong therapeutic efficacy, however they are sold to the public with dramatic health claims as if they were medically recommended.
In the past decade, there has been a public surge toward the over consumption of antioxidants with the impression that it keeps an individual healthy. Walking through the pharmacy section of any major super market, you see bottles upon bottles of supplements. The labels are eye-catching; telling the buyer all of the health benefits of a little pill. In the cold aisle, there are boxes of little packets that supposedly help you fight the common cold or flu. An individual may consume 2 Vitamin C packets a day in the hopes of staying healthy over winter. In reality, if you consume copious amounts Vitamin C, you end up excreting a majority of what 
you consume.
Your body needs a certain amount of each nutrient, and once it has enough, it gets rid of the rest. Over consumption can actually lead to negative consequences such as higher risk of lung disease for smokers. The evidence supporting the use of antioxidants as treatment for neurological disorders is ambiguous at best. Although there are benefits, they are not sufficient enough to treat or prevent neurological disorders.
Why then does the American public put so much stock in a little pill or packet of powder? We spend thousands of dollars on a natural “treatment” that has no proven effect. A healthy diet provides the needed nutrients without the high risk of overconsumption.
Sources
http://familydoctor.org/familydoctor/en/prevention-wellness/food-nutrition/nutrients/antioxidants-what-you-need-to-know.html
Images
http://www.amazon.com/Emergen-C-Super-Orange-Vitamin-30-Count/dp/B00016RL9G
http://www.dermalinstitute.com/us/news/2013/10/antioxidants-past-present-future/
http://healthblog.ivlproducts.com/blog/healthyliving/antioxidant-supplements-provide-abundant-energy
http://www.centrum.co.za/centrum-mynutrients-antioxidant
A link between insulin and Alzheimer's and a breakthrough cure?
Although a direct “yes” or “no” answer on whether there is a link between insulin levels and neurodegenerative diseases is desired, it is never that easy, because well… science. The further our knowledge extends on the brain and associated pathophysiology, the more we realize how interconnected and reliant certain systems and processes are on one another.
A third type of diabetes?
In the question of whether or not insulin is connected with Alzheimer’s, it is possible that the resistance to insulin within the brain is linked to this burdening disease. Insulin is more notably associated with the ever-rising diabetes. Type I and Type II diabetes are more commonly understood to be due to little or no pancreatic secretion of insulin and to peripheral insulin receptor resistance to insulin, respectively. Then there’s a Type III diabetes being proposed with a more common name, Alzheimer’s. Type III diabetes is hypothesized to be a result from central, instead of peripheral, resistance to insulin. Insulin is able to cross the blood-brain barrier (“BBB” a “safety border” between your blood circulating in your body and brain, protecting both from things not meant to be there) through passive diffusion and transcytosis in certain parts of the brain. Therefore, in type III, insulin is able to cross the BBB, but is resists binding to the receptors on the brain side.
How is insulin a bad guy? Irregularity in insulin signaling
I am focusing more on what is
called the
Forkhead box protein (FOXO) down at the bottom of the picture. What we want to have happen, is the FOXO gene to be functional, which leads to a cascade of transcriptions, resulting in longevity of neurons (what we want! Yay!), although too much FOXO can also be bad because too much of a good thing is a viable excuse here.. However, in the case of neuronal loss, insulin binds to the its respective receptor, a phosphorylation cascade happens, resulting in the inhibition of FOXO, therefore we don’t see the longevity of these neurons that we desire. We don’t want too much inhibition of FOXO, but we don’t want too much activation of it either, therefore its stubbornness to being regulated is what is burdensome. Once FOXO is inactivated (and subsequently removed from the nucleus), it has been shown to activate the POMC pathway – many more adverse impacts – uncaring of whether its actions are beneficial or not.
Curing age-related diseases
Although there is no set “cure” to neurodegenerative diseases like Alzheimer’s, there may be mechanisms with insulin involved (as a little glimpse is shown above). We can’t just shoot up patients with neurodegenerative diseases with insulin either, because it has an adverse effect throughout the whole body.
However, if you want to look into something hitting the forefront in neurochemistry, here is a cool link to a TED talk about Deep Brain Stimulation from a neurosurgeon, Andres Lozano. Although he talks more specifically about Parkinson’s disease, this treatment is starting to become more popular in medicine today and may be seen in the near future to activate the neurons we want activated for Alzheimer’s.
The Bigger Problem.. and a new cure?
I believe that one more TED talk is of necessity (and is shorter than the previous one…) Samuel Cohen speaks the bigger problem addressing Alzheimer’s (hint: lack of funding) and a HUGE breakthrough in the science realm where his laboratory is making recent breakthroughs.. You’ll have to watch.
Parkinson's Disease: My Old Narrow Mindedness of it Affect
As someone not particularly well read in the medicine world, I knew very little about Parkinson’s disease before, and really had only been exposed to the disease through Michael J Fox, and knowing he had it. By reading about it, I was surprised to find out that Parkinson’s disease is simply diagnosed by eliminating that it is not any other neurological diseases, and while it has certain characteristics like tremors, these can also be linked to other problems or diseases. Parkinson’s disease is interesting in that it affects both motor and non-motor symptoms. Parkinson’s is also largely linked to age and is considered almost a different disease when it is found in younger patients, as a lot of the characteristics of Parkinson’s are age related. Within Parkinson’s disease, neurodegenerations occurs, by mitochondrial dysfunction, oxidative stress, a poor proteins that become aggregated, all three leading to cell death in some way, thus leading to neurodegeneration. Within the pathology of Parkinson’s, there is involvement of Lewy bodies and in turn α-synuclein, as Lewy bodies are protein aggregates that are not normally in nerve cells, and α-synuclein is the main component of Lewy bodies. The motor symptoms that are present are linked to the death of dopaminergic neurons, thus there is not proper dopamine in the brain, which leads to loss of voluntary movements. Thus, many of the treatments for Parkinson’s pertain to the dopamine within the brain. What is interesting about these treatments is that they don’t really solve any problems, just temporarily allow controlled movement and disallow involuntary movements. The most common of these treatments is L-DOPA, the precursor to dopamine. L-DOPA is able to cross the blood brain barrier (whereas dopamine is not) and then be synthesized into dopamine once across. However, only 1-5% of the L-DOPA in the body actually makes it across the blood brain barrier, thus sometimes L-DOPA is also taken with enzyme inhibitors, as those can assist in causing the L-DOPA to cross the blood brain barrier or prevent dopamine from getting metabolized (thus the dopamine levels in the brain would be temporarily increased).
Parkinson’s disease is most known in the news in that most people know that Michael J. Fox has it, and I wonder if Michael J. Fox going out and being a spokesperson for the disease helps or hurts research funds. On one hand, I would assume more have heard about it than would, but on the other hand, we see someone with this disease seemingly functioning fairly well, which can lead to thoughts of the disease not being as life changing as ALS or cancer. I think that by having a celebrity spokesperson, there is chance that when people consider donating funds to a research organization that some may not think as Parkinson’s as a disease needing the additional research as much. As I really did not know much about this disease before, I really thought that Parkinson’s wasn’t as much of a terrible or life changing disease, because although I was aware it was around and was a problem, it never really clicked with me why I should care about the disease, I mean Michael J Fox seemed to be acting normal in public appearances, so how much affect could this disease have? What I didn’t understand was the types of treatment that one with this needs to get to be at that seemingly normal level, and the only non-surgical treatments available only subdued symptoms for a bit, not really working against the disease. It really surprised me to realize, that I had been judging a disease solely based on what I saw from one person, and mostly saw that person dealing well with Parkinson’s. Thus, while Michael J Fox is a good spokesperson, I wonder if sometimes this disease gets sidelined in people’s minds in comparison to some of the more deathly neurodegenerative diseases.
Insulin and Alzheimer’s, an Unexpected Link
You may have heard of Insulin before, especially if you know somebody who has Diabetes. Insulin is a hormone that helps the body use or store glucose in the bloodstream. People with Type II Diabetes have developed a resistance to Insulin and can suffer from chronic high blood sugar levels. An interesting connection to Alzheimer’s disease is that there is a link between defective insulin signaling and decreased insulin receptiveness in the brains of those with Alzheimer’s disease.
When Insulin binds to its receptor, two major signaling pathways are triggered, the PI3K and MAPK pathways. In patients with that have developed insulin resistance, the PI3K pathway is hindered while the MAPK pathway is left unhindered. The PI3K pathway is a critical pathway that plays an important role in food intake, liver glucose production, plasticity, learning and memory.
The PI3K pathway is critical for it has many benefits, one of the most pertinent, being its neuroprotective effects. The PI3K pathway inhibits glycogen synthase kinase (GSK3) activity and also inactivates the transcription activity of forkhead box protein O1 (FOXO1). This helps to decrease liver glucose production (through phosphorylation of FOXO1), to prevent the formation of Amyloid-Beta plaque buildups, and to prevent the hyperphosphprylation of tau proteins, the latter two known to be involved in Alzheimer’s disease.
As you can see from the paragraph above, there is a close and direct link between the PI3K pathway and both Alzheimer’s disease and Diabetes. By promoting the PI3K pathway, the inhibition of GSK3 could possibly provide therapeutic effects for patients suffering from both diseases. The use of insulin is commonplace for treatment of diabetes, but what is of interest to me is how it will be used for possible treatment in patients with Alzheimer’s disease. Furthermore, exploring alternate insulin related pathways to possibly treat Alzheimer’s disease would be interesting. Such treatment could include current treatment for Type II Diabetes. Understanding the link between insulin resistance and Alzheimer’s may bring us one step closer to curing this debilitating disease.
Information for this post taken from:
http://www.sciencedirect.com/science/article/pii/S1552526013029221