Concussions are a common injury that alters cognitive function. According the the CDC affects 1.3 million people a year in the US alone. They can have very serious health implications even though medically described as a “mild” traumatic brain injury (mTBI).
A high prevalence of concussions from sports related injuries and media can give the impression that only athletes are at risk. The recent movie “Concussion” even depicts the struggle the NFL and its players are facing due to the frequent and inherently violent collisions players sustain. However, concussions are also common with many non-sports related impacts such as falls and car crashes.
Knowledge of the underlying physiological mechanisms is limited, but progress is being made. Currently, sleep and rest are the only treatment for individuals who sustained a mTBI. A greater understanding of the injury at the cellular/molecular is needed to improve prevention, therapy, and long term cognitive effects of repeated concussions.
Concussions are caused by an impact that usually involves a whiplash motion where the brain bounces, twists, and stretches. Symptoms can vary for each individual injury, but can include headache, nausea, lethargy, memory loss, dizziness, and emotional changes. These effects can take weeks to resolve with proper care.
I have personal experience from a high school football injury during a homecoming game. I was defending a pass play in which I leaped for the ball while another player took out my legs. I went head-first to the ground with a forceful impact. Following the play, I had memory loss of the few hours after and only know what happened due to the game film.
The following weeks were filled with dizziness and lethargy. I felt like I could not escape a fog like being extremely sleep deprived. Occasionally I would go to another room in the house to do something specific and completely forget what I was trying to accomplish when I got there. I attempted to return to play the following week and was not allowed regardless of how important my sixteen-year-old self-believed it to be. At the time, I did not realize the magnitude of the risk that returning posed to my health.
The post-concussive brain is susceptible to a second impact which may result in prolonged healing time and permanent damage. Often no visual evidence like a bruise is evident and can create a sense that nothing is in fact wrong. Some individuals believe this and do not rest and return to potentially dangerous activity soon after the initial injury. This can be deadly mistake; second impact syndrome can occur if another significant impact is received before the brain is healed. Extreme and rapid swelling occurs and the brain losses control over cerebral blood flow eventually leading to severe cerebral edema.
Ongoing research works to elucidate the physiological mechanisms and long term effects underlying these mTBI’s. A better understanding could provide more effective prevention, detection, and therapy for the millions of affected individuals a year. Researchers have discovered that damage to the neurons creates ionic fluxes and unsystematic release of the excitatory neurotransmitter glutamate. This disrupts the cellular environment creating stress, impaired axonal transport, and improper signaling in the brain. Making connections between the hard science and symptoms will lead to improved prevention, therapy, and long term outcomes of mTBI.
Simply being conscious to the reality of concussions is simple step that everyone can do to make informed decisions in the event of a possible mTBI.
Zinc and the Immune System: The Secrets of Autism Spectrum Disorder?
Autism Spectrum Disorder (ASD) is a disease that affects about 1 in 68 children in the United States, according to an ADDM Network Survey from 2012. ASD includes disorders like Asperger’s, Autism, Pervasive Developmental Disorder, and Childhood Disintegrative Disorder, that all have slightly different levels of cognitive and learning impairment, variations in behaviors, and other symptoms. There are two main types of behaviors in children with ASD, although not all people will display all the symptoms, and some may exhibit several of them. The first is restrictive or repetitive behaviors, the second is social communication/interaction behaviors. Sometimes diagnosis can be tough because it is difficult to discern, for example, if a child falls in the lower-functioning end of Asperger’s, or the higher-functioning end of Autism, as they fall on a spectrum. Even with some of the impairments that these children have, they often have great strengths and abilities in one subject or aspect of their lives, such as math, music, or other things.
The prevalence of ASD in the United States is increasing. Some argue that this could be due just to higher numbers of diagnoses as awareness has risen. There is no specific cause that has been identified for ASD, but there are genetic factors that are thought to be responsible for ASD occurrence, although they are not able to account for all cases. There appears to be some environmental factors that also contribute to the number of cases of ASD or increase the risk for it, especially if some of those autism-related genes are present.
The article that we read in class identified two main environmental factors that are thought to contribute to cases of ASD – zinc deficiency and dysfunctional immune system. It is thought that they contribute to dysfunctional excitatory signaling as they inhibit correct structure and development of synapses and their receptors and cause some dysfunctional kinase signaling. Many of the genes implicated in ASD either need zinc or are involved in zinc homeostasis in the body. Low levels of maternal zinc in pregnancy can cause immune system dysfunction, which can make the fetus more susceptible to infections while in utero. This can in turn cause some developmental problems in the child and their brain.
As mentioned, zinc deficiency contributes to immune system abnormalities. Obviously this can make the child more susceptible to diseases, but inflammation can have detrimental effects on the body when it goes on for too long. It can damage developing cells and contributes to neural plasticity at synapses.
These two main environmental factors affect each other, but they are in interplay with other environmental and genetic factors as well. Things such as prenatal and perinatal stress, parental age, exposure to toxins, prenatal infections, and melatonin deficiency can all contribute to immune system abnormalities. Malnutrition, copper overload, and melatonin deficiency contribute to zinc deficiency.
Mutations in genes can affect zinc homeostasis as well, and increased age of the parents gives a higher chance for mutations. Exposure to toxins and zinc deficiency also may cause genetic mutations, and when they are in those genes that encode for scaffolding proteins, receptor proteins, or signaling cascade proteins, it does not allow for proper synapse function, contributing to the expression of ASD.
Thus, it is hard to pin-point the exact cause of ASD, but it is obvious that there is important environmental contributors along with the genetic components of the disease. It will be important to educate parents about proper nutrition so they get the nutrients they need, such as zinc, to help the baby develop properly and protect against maternal and fetal infections. It will also be important to be aware of the possible effects that exposure to toxins or other environmental agents may have on the body as well. As more is learned about zinc, the immune system, environmental contributors, and their interactions with autism-implicated genes, maybe someday we will be able to prevent or even cure people with ASD.
What Does Concussion Do to Our Neurons?
Concussions are difficult to spot and treat without an obvious injury to the brain. A brain scan will not show bleeding or large-scale damage. But concussions can cause serious injury to the brain at the cellular level.
Ion leaking is one dramatic example of the effects of concussion on the brain. The impact of a concussion tears tiny holes in the membranes of neurons. Ions, because they are only single atoms, are able to uncontrollably flow in and out of the cell through these tears. Neurons use sodium ions to carry electrical signals. They take in sodium at exactly the right time to create an action potential. When sodium rushes in all at once, neurons become stuck in an inactive state. Ion flux may explain the migraine symptoms that can come with concussion. Similar movement of ions occurs in migraines, and people with a history of migraines are more likely to have worse concussion symptoms.
A concussion can send the brain into an energy crisis. Moving ions in and out of cells costs a lot of energy, even for a healthy brain, because it takes energy to run the tiny pumps that transport the ions. After a concussion, the brain needs even more energy. The brain works extremely hard to restore the balance of ions. Since blood flow to the brain is reduced after a concussion, the low supply of energy makes the high demand worse. Energy crisis probably explains why getting a concussion makes the brain more sensitive to a second concussion. Research has shown that if a second concussion happens after glucose metabolism rises back to normal, the two concussions act as separate small injuries instead of one massive injury.
The stretching forces of a traumatic brain injury are known to damage axons in the brain. Axons are the long, thin parts of neurons that carry signals, kind of like wires. It makes sense that these delicate structures are especially vulnerable to concussion. When the brain bounces against the skull, axons can partially tear or completely disconnect from neurons. Myelin, the fatty insulating layer on axons, gives some protection against concussions. That might explain why young children are more vulnerable, since the process of making myelin happens early in life. Axon injury is probably an important factor in the slowed thinking that comes with concussion.
Some of the more subtle signs of concussion, such as migraine or mental fogginess, might be too slight for someone to know that their brain is seriously injured. As we learn more about the causes of concussion symptoms, hopefully we will be able to develop accurate tests for concussions.
Parkinson’s – a Disease Divulged
Parkinson’s – A Disease Divulged
You never expect it will happen to you. When it does, your whole world seems to start spinning in a different direction. One morning, as I was getting ready for school, my mom came downstairs in a mess of tears, and through sobs told me that her brother had been diagnosed with Parkinson’s disease. Even though I wasn’t really sure what Parkinson’s disease was at the time, I was still devastated by the news. A very close family member of mine had been diagnosed with a disease.
As devastating as this new was in the beginning, I needed to find a way to cope. I couldn’t spend every time with my uncle feeling bad about his diagnosis. Five years later, I put his diagnosis behind me and treat my uncle the same as I had before. We still joke around just as often and dance around the kitchen at my grandparents’ house. Every now and then his hand will shake with a tremor and I am reminded of the disease, but he is luckily still functioning at full capacity.
For my generation (young adults), Michael J. Fox’s Parkinson’s actions are before our time. Therefore, we are not as aware of the disease or what it entails. So for those who aren’t aware, this is what researchers and doctors believe is at the root of Parkinson’s.
Alpha-synuclein and Lewy Bodies
In the brain region called the substantia nigra, neurons get a buildup of misfolded proteins. The substantia nigra is a location in the brain that holds a considerable amount of the brain’s dopamine.
When a specific protein called alpha-synuclein gets phosphorylated, it isn’t able to get broken down. In Parkinson’s disease, alpha-synuclein is hyperphosphorylated causing them to aggregate. These aggregations are then called Lewy bodies. A bunch of Lewy bodies in a neuron cause the neuron to die and a loss of dopamine. Interestingly, it seems that most of these problems affect the communication between intent of movement and the actual movement. This causes the patient to have slowed and rigid movements and tremors.
Although this disease spreads throughout the body over time and can even lead to death, depending on the degree of severity and treatment, it can take several years for it to become a negative impact on daily routines. The current treatment for Parkinson’s is the use of a drug called L-dopa. This drug helps to reintroduce dopamine in the substantia nigra, helping the signal for movement to be improved, which in turn reduces symptoms. Doctors actually will prescribe a patient a high dose of L-dopa to diagnose Parkinson’s. If the patients symptoms decrease, the diagnoses is considered confirmed.
You never expect it will happen to you. A diagnosis of someone that is close to you will have a tremendous effect on your life, but learning about a disease and how to cope with it will not allow the disease to hinder your relationship. So for now, I will keep on dancing with my uncle in the middle of my grandparents’ kitchen as long as I can. Parkinson’s will not take that away from us.
Brain image: https://s-media-cache-ak0.pinimg.com/736x/30/4e/ba/304eba7a5b82d65d8b1b43242343e44b.jpg
Since Vaccines Don’t Cause Autism, What Does?
Since April is Autism Awareness Month, it seems very fitting to learn about!
Autism is characterized by difficulty communicating, repetitive or obsessive behaviors, and sensitivity to light and materials. According to the CDC, 1 in 68 people in the US are diagnosed with an autism spectrum disease. Breaking that up even further, 1 in 42 boys and 1 in 189 girls. Children can be diagnosed as early as 2 years old, however it is usually not until age 4 or 6 in the case of Asperger’s disorder.
So why the gap between the genders? Signs of Autism Spectrum Disorder are often displayed more in men and boys such as the repetitive behaviors and lack of communication skills. However, girls tend to internalize behaviors are more likely to exhibit shyness that may be overlooked. Often times their fixation is something that other girls are likely to enjoy as well such as horses or animals. Females also tend to be more social beings and have more verbal skills then males which could contribute to the oversight. There is a hypothesis that a genetic contributor to the cause of autism is on the X chromosome (pictured in pink). Because males only have one, they are more likely to exhibit autistic tendencies than a girl with two X chromosomes.
Y and X chromosome
But beyond that, what is the cause? There are many misconceptions about its cause because it is very poorly understood. There are likely many contributing factors such as the environment, especially during development. If a mother gets sick or gets an infection during the pregnancy (especially during a critical time) it can increase the child’s risk for autism. Immunity problems in the mother, such as an autoimmune disease or fighting an infection, can produce antibodies in her body that can cross the placenta and interfere with fetal brain development. Often times if there is a disruption or abnormal function of the immune system in the fetus it can lead to inflammation causing even further damage.
An IgG that is able to cross the placenta.
It has also been seen that zinc deficiency during gestation plays a role in abnormal cell function as well. Zinc is very important in cell division, protein interaction, and healing. Low zinc levels have been found in people with autism. It is important to get the proper amount of zinc (12-13 mg/day) while pregnant or breast feeding.
Age of parents is also a risk factor, especially if the mother is older than 35 and the father is older than 40. It is important to also include genetic contributions as a potential contributing factors. There are mutated genes associated with autism, but no definitive relationship. Interestingly, some of the genes in question are related to zinc function in the body.
It is important that people are properly educated as to what is known about autism. When reading information about autism and its cause it is essential to check the credibility of the source and the studies that support it. People with autism can be very highly functioning, or may need a lot of help – that is why there is a spectrum. It is important to be respectful, understanding, and patient if people with autism have trouble communicating. We are making progress when it comes to awareness. Meet Julia, a little girl with autism who is the newest addition to the cast of Sesame Street!
The Great Debate: Vaccines and Autism
Our topic of the week is Autism, which means I get to get on my favorite soapbox: vaccines and Autism. There is no link between childhood vaccines and the development of Autism. Let me repeat that: vaccines DO NOT cause Autism. This is not simply my opinion; it is fully backed by sound scientific evidence.
Let us first examine the retracted Wakefield study. Published in 1998, Andrew Wakefield examined 12 children for cognitive symptoms of Autism and gastrointestinal disorders, with the goal to link these symptoms to something in the environment that they were all exposed to. There are some obvious initial flaws of the paper, without even reading more than the abstract. First, Wakefield had a sample size of just 12 children, with no negative controls. Any results or statics from a group this small are simply speculative and cannot be taken as scientifically sound conclusions. Of these 12 participants, 11 were male. Looking at the demographics reported by the CDC, it is clear that boys are statically more likely than girls to be diagnosed with Autism (1 in 42 in boys and 1 in 189 in girls). It is likely that Wakefield knew this and took advantage of this trend when selecting an almost exclusively male sample, knowing that by doing this, he would increase his likelihood of having children with Autism present in the study. Secondly, the symptoms were reported to the researchers by the parents of the children, not by trained medical professionals. While parents know their child and their child’s behavior better than anyone else, they are not equipped to make a medical diagnosis.
After the publication of the Wakefield paper, the scientific community began to examine their findings to validate them and expand on them, which is what often happens with new findings in the scientific community. First, other groups of researchers were unable to replicate Wakefield’s findings, something that is critical in scientific research. In fact, Wakefield himself was unable to replicate his own findings, with a different group of participants. Next, Wakefield failed to disclose a critical conflict of interest. He had been paid by a law firm that was planning on suing the makers of the MMR vaccine. This fact alone is enough to cast reasonable doubt to the validity of his claims. Additionally, according to journalist Brian Deer, Wakefield was accused of, “falsifying medical histories of children and was essentially concocting a picture, which was the picture he was contracted to find by lawyers hoping to sue vaccine manufactures and to create a vaccine scare.” He also failed to disclose that he had been developing an MMR vaccine that would be a direct competitor to the one that he claimed had been causing Autism.
Perhaps most concerning was Wakefield’s treatment of his subjects, all children who may have developmental disabilities, making them particularly vulnerable. First, he paid children for their blood samples they provided, off the record and without providing them or their guardians with informed consent forms. He also subjected his subjects to colonoscopies, lumbar punctures, and other medical procedures, without the approval from an institutional review board (which is illegal). These review boards are critical in evaluating research protocols and protecting the rights and safety of the participants. The tests that the subjects were subjected to would be traumatizing for any young child, but particularly so for subjects with developmental disabilities.
After a 2004 investigation by the Sunday Times, the majority of Wakefield’s co-authors removed their names from the paper. In January of 2010, an independent panel investigated the paper and found Wakefield guilty of dishonesty and the abuse of developmentally disabled children. The Lancet retracted Wakefield’s paper and his medical license was revoked soon after.
Now, lets pretend that vaccines cause Autism (they don’t). One causal agent that popular media likes to flaunt is mercury. Thimerosal, a mercury derivative that used to be used in vaccines as a preservative. Without this preservative, bacteria could grow in vaccines, which could be deadly to the recipient. It is important to understand that timerosal contains a form of mercury called ethylmercury. Unlike methylmercury, which is the form of mercury that damages the nervous system, ethylmercury is broken down by the body and is safely and quickly excreted from the body. Strict, valid, and stringent scientific research has shown that ethylmercury is not harmful to the body and vaccines with thimerosal do not cause Autism. Not convinced by the science? Thimerosal was removed from all vaccines, except a few types of flu shots between 1999 and 2001. Even if thimerosal was causing the development of Autism (it wasn’t), it is no longer even in our vaccines anymore.
So what does cause Autism? How can parents protect their children? Researchers are still working to figure that out. It appears that there is both an environmental factor and a genetic factor. It may have something to do with the levels of zinc and copper in our bodies, or perhaps the types of bacteria we harbor in our gut, or even maternal infection or antibodies during fetal development. It is understandable that parents want to do everything they can for their child to avoid harm, sickness, or disability. Autism is unavoidable but vaccine preventable diseases can be avoided with a safe and effective vaccine. I’m not a parent, but I know which choice I would make for my child, and in the face of insurmountable scientific evidence, I would choose the vaccine any day.
Dear Antivaxxers,
It is very possible that your choices will prevent your child from developing autism, but those regarding vaccines will not. Recent research suggests a plethora of environmental prenatal factors that play an important role in a child developing autism. These include viral infection, zinc deficiency, abnormal melatonin synthesis, maternal diabetes, prenatal and perinatal stress, toxins, and parental age. But note that if these are prenatal, then administration of a vaccine once a child is born will not affect whether autism develops.
Let us observe these factors more deeply.
First, viral infection (of a pregnant mother). How could an infection cause autism in an unborn child? The answer lies in antibodies. Antibodies are a part of the body’s natural defense mechanism, meant to identify and eradicate foreign objects. And so it makes sense that, during a viral infection, a mother’s immune system increases its number of antibodies. This is great for the mother to stay alive, and these antibodies do not affect her in any negative fashion, but the fetus responds quite differently. Because antibodies can cross the placenta, they find their way into the bloodstream of the fetus, and through the developing “blood-brain barrier”. Here they disrupt normal brain development, and just so, may cause autism. Beware even further, that autoimmune diseases and intense allergies may cause a similar result.
Zinc deficiency has also been shown to increase risk of autism in developing fetuses. Take your vitamins, pregnant mothers. Because zinc is an important element in cell metabolism (namely gene regulation), a lack of the metal will force cells to develop poorly. Even further, high levels of copper can displace zinc and cause similar effects.
Melatonin synthesis is, of course, slight more out of one’s control. But the fact remains, abnormality in its synthesis is correlated with increased rates of autism. The results of this may be seen in the unique sleep-wake cycles of people with autism, as melatonin plays an important role in regulation of circadian rhythms.
Maternal diabetes is quite certainly out of the control of all parties, but it has been shown to be correlated with autism in children. The pathology is unknown however, and more research is necessary to know more about this factor.
Prenatal and perinatal stress may seem difficult to avoid, as having a bowling-ball-and-a-half hanging on your abdomen will certainly cause discomfort. But the increased levels of glucocorticoids and cytokines will not be beneficial to your child. These hormones can cause the immune system to turn into overdrive, and just as with the viral infections, we have seen why that is bad news.
Toxins are certainly bad for adults as well as children. Mercury, lead, thalidomide, valproic acid, and many other chemicals are shown to affect the human brain in adverse ways. With that said, adults are able to handle small doses associated with everyday life. But fetuses? Not so much. Of course, this was part of the scare with vaccines, as they contained minute amounts of mercury. Thankfully, however, this mercury has since been removed, and even if it were not, the mercury had been chemically bound in a non-toxic form.
Parental age can be a very important factor as well. As men age, their gametes (sperm) develop more and more mutations which are then passed on to children. Mutations of any sort are more-than-likely bad for an organism, and can certainly cause brain development issues. Increase age of mothers also has a correlation with autism, though likely through autoimmune disorders and pregnancy complications rather than mutations.
All of this shows that how we behave as “pre-parents” matters to the developing fetus. However, this also shows that children are born with autism, and are not going to develop the disorder from an injection after birth. Vaccinate your children; you will save lives.
The Life and Times of Parkinson’s – the History of Disease
While there are many diseases out there that are new or are reemerging to reek havoc on human health, there are some that have been a part of the human experience since the beginning. Strangely enough, Parkinson’s disease is on the list that has been documented for thousands of years. While the disease was first officially described to Western audiences by its namesake James Parkinson in 1817, there is indications that it has been documented in Ancient China and India in 1000 B.C. However, the first to really study it at any depth was Jean Martin Charcot in the 1880’s and was the first to describe the spectrum of the disease, from tremors to the rigidness. Another great contribution that Charcot made to the study of the Parkinson’s was a way to differentiate it from other neurodegenerative diseases with similar symptoms.
William Gowers also made huge strides in the understanding of Parkinson’s, finding that the disease is more prevalent in men than it is in women. However, it wasn’t until the 1960’s when scientists were able to understand the underlying biological mechanisms that were causing Parkinson’s. It was previously known that Parkinson’s patients had low levels of the neurotransmitter dopamine. But why that was remained unknown until they found that dopaminergic neurons found in an area of the brain called the substantia nigra were dying. With this knowledge the drug Levodopa (L-DOPA) was created to treat Parkinson’s symptoms and has ever since been the ‘go to’ drug for Parkinson’s treatment. However, the search for a cure is still ongoing.
Sources:
http://www.parkinsons.org/parkinsons-history.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234454/
Can We Cure It All?
A lot of medications that we have heard of today that are designed to make diseases more livable don’t actually treat the source of the problem. More often than not, they treat the symptoms, but not necessarily the cause. From a logical perspective, this doesn’t make the most sense. When you put out a fire, you aim the extinguisher at the bottom, where the source of the fire occurs, not at the flames themselves.
Granted we are trying to do the best that we can. For some diseases we don’t even know what the exact cause is, and some diseases have so many possible causes that it would be impossible to treat each individual case.
Consider Parkinson ’s disease; PD is a neurodegenerative disease, which like many neurodegenerative diseases, involves the development of a conglomeration of buildup in different areas in the brain. In PD, an abundant protein called alpha-synuclein is phosphorylated and then accumulated to become a Lewy Body. Lewy Bodies do not occur in a healthy brain, and they are essentially just little knots of trash. These aggregations can cause cell death, specifically the death of dopaminergic neurons. These neurons are involved with the synthesis of dopamine, and essential substance.
There are SO many causes of PD, that it is likely that we’ll never be able to cure all forms of it. Basically, if any kinase is mutated so that it over phosphorylates alpha-synuclein, PD can occur. Or if any protein that helps to get rid of excess proteins in the brain is mutated, PD can occur. Luckily, PD isn’t very deadly, and the most common medication administered (a dopamine precursor compound) helps to reduce the tremors which are common with PD.
Like PD, we don’t have cures for most neurodegenerative diseases, like Alzheimer’s or ALS. These diseases also likely have many many different causes, but it is possible that these causes are all relatively similar. It is essential that we continue funding research on these diseases, if we ever hope to find a cure.
Don’t Judge an Enzyme by Its Structure
Hmm…that title was a bit far-fetched. It was supposed to play off the adage “Don’t judge a book by its cover”. Regardless, I will get to my point: new research Parkinson’s disease has revealed a fascinating connection between seemingly unrelated proteins.
Parkinson’s disease is a long-term disease characterized by motor neuron degeneration, but in late stages also causes dementia (the picture below is from an 1886 book on neurological diseases). The motor symptoms result from the death of cells in the substantia nigra, a portion of the brain involved in movement and motor planning. The result of this is lowered levels of dopamine within the substantia nigra.
While the exact cause of the degeneration is unknown, years of research has been placed on the Lewy-bodies (congregations of proteins) that form within cells. Patients with Parkinson’s have an elevated level of these Lewy-bodies in their neurons, so it is natural to assume they play an important role.
A very prevalent protein involved in the formation of Lewy-bodies is α-syneuclein, the long, stringy protein pictured below. This protein’s main role in human cells is only vaguely understood (though it seems to be important in managing the bird songs of zebra finches). It is possible that the protein is an inhibitor of phospholipase D2, which means that more of this protein would result in lower levels of phosphatidic acid and choline, which are neurotransmitter precursors.
The way α-syneuclein accumulates into Lewy-bodies is through a process called aggregation. If the protein gets phosphorylated (usually this means “marked for degradation”) when it is not supposed to, it can clump with others to form these aggregates. Even further, the “prion effect” is seen with this phosphorylated protein, meaning that if it runs into healthy proteins, it can change them into unhealthy proteins, compounding aggregation.
So how do these healthy α-syneuclein’s get phosphorylated into their unhealthy versions in the first place? The answer may lie in GRKs.
Acronyms are great, aren’t they? GRK stands for G-protein coupled receptor kinase, which is a collection of words that essentially means “cell receptor deactivator”. These enzymes cycle through a cell and find cell receptors that are being activated too often. Since the cell no longer wants these activated, the enzyme phosphorylates it, which marks the receptor for death.
Here we again see the word “phosphorylates”. It was just this process that began the aggregation of α-syneuclein into Lewy-bodies. Recent studies have shown that these GRKs are able to phosphorylate α-syneuclein even though their structures insist that they should not. Prior to this research, there was no reason to believe that a GRK would play a role in Parkinson’s disease, as the enzyme regulates pathways quite unrelated to aggregation of proteins.
But here we see it, an enzyme phosphorylating a protein that its structure insists it should not. This is precisely where the title of this post fits in. It is so easy for researchers to think that they know everything and skip over some ideas because they believe them to be invalid.
In the end, however, research needs to be thorough for its own sake. The world works in very mysterious ways sometimes, and we need to check even the most remote possibilities if we are indeed set on learning more about this universe. Perhaps Parkinson’s disease may be cured because a few people decided to observe the effect of a random enzyme on α-syneuclein, even though the science told them they shouldn’t.