Parkinson's and Fruit Flies

Researchers have discovered a new gene within fruit flies associated with the PINK1 and PARKIN genes, which are both heavily associated with Parkinson's disease. Because fruit flies carry 75% of the genes that are effected by disease, it is easy to use fruit flies to compare The new gene is named ATF4 and is vital in the health of mitochondria and can be used to control the expression of PINK1 and PARKIN.  People with Parkinson's have been found to have problems with their mitochondrial health.
The lead researchers on the case discovered that using bioinformatics, they were able to control the expression of the ATF4 gene. By making the gene expression more prominent, researchers noticed better health of mitochondria and reverted the damage done to the brain from the disease. By turning the gene off, there was a problem with the fly's movements, they didn't live as long, and the mitochondria in their brains was being more and more dysfunctional.
I would love to see the effects of encouraging this gene to be expressed in humans, as I do believe it can help many people regain control of their lives.

About Parkinson's

Article

Replacing damaged brain cells reveals a possible cure for Parkinson's Disease



Parkinson's disease (PD) is a chronic disorder that gets increasingly worse over time. It involves the malfunction and death of vital nerve cells located in the brain. Patients with PD suffer with symptoms like tremors (of the hands, arms, legs, jaw, and face), impaired posture and coordination, bradykinesia (slowness of movement), and more. In recent months, researchers have discovered a way to transform glial cells of the brain into dopamine-producing brain cells. The dopamine these cells produce is a neurotransmitter that sends signals to the substania nigra, a part of the brain that is associated with movement and coordination as well as other areas of the brain. The dopamine-producing cells in the brain of an individual diagnosed with Parkinson's are damaged which leads to a lack of dopamine in parts of the brain and cause tremors, impaired balance and coordination, and slow movement. Neurons from fetal mid brain tissues were the first form of transplant experimented with, however, due to the difficulties of obtaining these neurons, stem cells or reprogrammed cells are often used.

Professor Ernest Arenas and his colleagues of the Karolinska Institute of Sweden have furthered the research of transplanting and study the process of reprogramming cells, which avoids transplanting cells in the brain by converting existing cells into other cells, like dopamine-producing cells. The researchers combined certain genes that shape dopamine cells with transcription factors. The research conducted by these scientists and the works published is Nature Biotechnology has proven to be a significant step forward in the process of curing the millions of people who suffer from Parkinson's worldwide. If further studies take place, even more genes that promote the generation of dopamine cells and will give an even larger possibility of terminating Parkinson's disease.

A cure for Parkinson's? Replacing damaged brain cells shows promise

This article is about a new technique that has hopes of improving Parkinson's disease. This disease involves a lower number of dopamine being introduced into the system, which causes the physical tremors and decreased sense of balance in the individual. The new technique is to transform non-dopamine producing brain cells into brain cells that can produce the chemical. This is being done by changing the astrocytes cells (the cell in the picture above) to replace the damaged dopamine cells. This process was tested on mice and the results were successful. My opinion on this is that this is a good step in the right direction. In the article it mentions that this technique needs to be developed further if going to be applied to humans. I completely agree with that and am hopeful that this can become available for human patients sooner rather than later.


Medical News Today 


Parkinson's Disease 

Using Shark Steroid to Fight Parkinson's Toxin

A team from Georgetown University Medical Center found that a synthesized steroid that mimics one produced by dogfish sharks was able to prevent the buildup of the protein alpha-synuclein. Alpha-synuclein clustering is the harbinger of neurodegenerative diseases such as Parkinson's and dementia with Lewy bodies. Scientists used C. elegans, a nematode that has been genetically modified to produce the lethal protein, thus causing paralysis and cell damage as it ages. Using their nematode animal model, researchers discovered that squalamine reduced the virulence of alpha-synuclein by removing the protein from nerve cell walls in the C. elegans test subject. Scientists hope that squalamine may be able to be used as a therapeutic aid in patients who have neurodegenerative diseases. 

I thought that this article was interesting because medicines have been created using plants and animals. Parkinson's disease is painful and uncomfortable for many patients, and if a steroid that's naturally found in dogfish sharks can be used to treat the symptoms caused by the disease, then so be it. It would be a great step in the treatment and possible prevention or cure for Parkinson's. 

https://www.sciencedaily.com/releases/2017/01/170116160556.htm

https://gumc.georgetown.edu/news/steroid-originally-discovered-in-the-dogfish-shark-attacks-parkinsons-related-toxin-in-animal-model

Genes and Parkinson's Disease

Researchers from King's College London have been able to identify a gene linked to nerve function which they believe could provide a treatment target for 'switching off' the gene responsible for neurodegenerative diseases such as Parkinson's.  Their study was conducted using the larval stages of Drosophila.  The nerve cells were genetically engineered to create a green flourescent protein, which allowed these researchers identify nerves with damaged mitochondria.  "A gene called HIFalpha was found to regulate the nerve signals from damaged mitochondria and, when this gene was 'switched off' by the research team, nerve function in flies with Parkinson's disease was restored.  By deactivating the HIFalpha gene, the early failure of nerve cells caused by mitochondrial damage was prevented." (King's College London)  With these findings, researchers now have a greater understanding of how nerve cells work.

I really enjoyed this article and found it to be very promising for patients suffering with these 'incurable' diseases. With this new research I hope that scientists are able to create a drug that will give positive results and relief to patients.  Maybe with this research a cure for these diseases, including Parkinson's, will arise!

Check out the article here. To read more on Parkinson's disease click here.

New Cellular Defense Mechanism against Stress

     

     Scientists studying neuronal malfunctioning, long thought to be a result of a cell’s reaction to stress, may have unlocked a new understanding and even a treatment plan for the future. Science Daily explains that neurodegenerative diseases such as Alzheimer’s and Parkinson’s are caused in part by a cell’s reaction – or lack thereof – to stress. Scientists from Harvard and NYU have identified a protein modification that signals for the cell to begin protein synthesis, in turn strengthening and protecting the cell from attack.

     Oxidative attack – the focus of this research – is when cells are exposed to hazardous conditions (pollution, cigarette smoke, radiation). Exposure to these stimulates the stress response in cells to begin degradation of weak or damaged proteins. It is speculated that with less impaired proteins in the way, the cell can begin protein synthesis and restructure itself. Using this new research, scientists may be able to harness the removal of such proteins and one day focus on a treatment plan for neurodegenerative diseases. 

Coffee Help Preventing Parkinson's

Neurodegenerative diseases like Parkinson's are less common for those who drink a lot of coffee. Since illnesses like Parkinson's are intertwined with both genetics and environmental factors, the habit of having coffee is encouraged for prevention. A research team has identified in a study of a million genetic malformations that a variant of GRIN2A protects against Parkinson's. The corresponding protecting play a huge role in many neurodegenerative diseases.

A dopamine receptor that manages the amount of calcium enters a cell is combined with caffeine. As a part of the reward system, dopamine involved with caffeine has been thought to not reward individuals with certain genetic variations the same. GRIN2A has recently shown a recent connection to such a genetic predisposition.

http://www.sciencedaily.com/releases/2014/07/140710081304.htm
 https://www.google.com/search?q=Coffee&biw=1252&bih=602&source=lnms&tbm=isch&sa=X&ei=tvh3VJnKFcfOsQTbiIKIBA&ved=0CAcQ_AUoAg#facrc=_&imgdii=_&imgrc=OU_c34mZ_rSTvM%253A%3BgacBYV22Zty6rM%3Bhttp%253A%252F%252Fdreamatico.com%252Fdata_images%252Fcoffee%252Fcoffee-3.jpg%3Bhttp%253A%252F%252Fdreamatico.com%252Fcoffee.html%3B1536%3B1047

Deep Brain Stimulation May Unlock the Cure to Tourette’s Syndrome

Tourette’s syndrome is a neurological disorder that causes individuals to make involuntary movements and loud noises. There is currently no cure for Tourette’s syndrome; however, specialists at the University of Florida's Center for Movement Disorders are looking to change that. Specialties at the center are performing experimental surgery in Tourette’s patients.  The procedure, deepbrain stimulation (DBS), is currently used in patients with movement disorders such as Parkinson's disease or tremors.

Deep brain stimulation is based off the delivery of electricity and works by implanting small electrodes into the brain in order to stimulate affected regions in patients with movement disorders. The electrodes are attached to an impulse generator and the generator, which is also referred to as a pacemaker, provides electrical impulses to the affected regions of the patient’s brain. The connections between neurons are affected by the impulses which stop the abnormal activity that the patients are presenting with.

While DBS has been performed in over 100,000 patients since 1997 it has never been performed in Tourette’s patients. The underlying neurology in Tourette’s patients is different from that of other conditions treated with DBS because it combines both emotion and motor activity. Specifically, in Tourette’s patients the movement is not there all the time; the patients have a buildup, tic, and an urge and until they can move the patients do not feel better. The only current available treatments for Tourette’s syndrome are behavioral therapy and drug medications; however, these treatments only alleviate the severity of the tic they do not prevent the tics all together.

In September 2014 DBS was performed in a patient with Tourette’s syndrome for the first time. Additionally, the patient had a new grid-like device implanted on top of her brain. This device is intended to gather information from the patient’s brain that can hopefully lessen her tics, and possibly someday stop them. Over the next six to twelve months the patient’s brain activity will be monitored with the grid providing key insights into the underlying cause of her Tourette's syndrome. Understanding the underlying causes of the syndrome will allow doctors to regulate the electrical impulses to in order to manage and hopefully eliminate the tics all together.

This article really caught my attention me because I am very interested in neurological disorders and learning more about them. Tourette’s syndrome is an interesting and difficult disorder because of both the physical and emotional combination. It will be interesting to see over the next several months how well DBS works in this patient. I am hopeful that this procedure will be the next step in learning not only more about the disorder but will be able to eliminate the symptoms experienced by Tourette’s patients.  

Main Article: http://www.cnn.com/2014/10/27/health/deep-brain-stimulation-tourettes/index.html?hpt=he_bn3

Secondary Article: http://tsa-usa.org/dbs/DBSfall09x.html

Researchers Discover New Evidence that High-Risk Parkinson's Mutation are Reversible

Researchers, led by Dr Kurt De Vos and Dr Alex Whitworth, from the Department of Biomedical Sciences at the University of Sheffield have discovered vital new evidence on how to target and reverse the effects caused by one of the most common genetic causes of Parkinson’s. Specifically, it is known that mutations in the LRRK2 gene carry a well-established link for Parkinson’s disease; however, the basis for this link still remains unclear today.

The team of researchers, through their research with Drosophila (fruit flies), found that certain drugs, deacetylase inhibitors, can fully restore movement problems observed in the flies carrying the LRRK2 Roc-COR Parkinson's mutation. Specifically, these drugs target the transport system and reverse defects that are caused by faulty LRRK2 within nerve cells.

Dr. Whitworth was quoted as saying: “By targeting the transport system with drugs, we could not only prevent movement problems, but also fully restore movement abilities in fruit flies who already showed impaired movement marked by a significant decrease in both climbing and flight ability."

The LRRK2 gene produces a protein that affects multiple processes in the cell; this protein binds to microtubules which are the cells transport tracks. Defects in the transport system have been linked to be contributing factors for Parkinson’s disease. The researchers investigated this link and found that certain LRRK2 mutations affect transport in nerve cells. The mutations led to observed movement problems in the fruit flies. The group of researchers used several approaches which showed that preventing the association of the mutant LRRK2 protein with the microtubule transport system rescued the transport defects in nerve cells which in turn alleviated the movement deficits in fruit flies.

Certainly there needs to be more significant research done before more definitive results can be drawn from this research. However, the research results are very promising especially since there are currently no cures for Parkinson’s disease. Therefore, any research, albeit small at the movement, provides encouragement that there will one day be a cure for this degenerative neurological condition.

Article Link: http://www.sciencedaily.com/releases/2014/10/141015090446.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily%2Fhealth_medicine+%28Health+%26+Medicine+News+--+ScienceDaily%29

Related Link: http://www.medicalwebtimes.com/read/effects_of_highrisk_parkinsons_mutation_are_reversible_study_in_animal_model_suggests/

Human Leukocyte Antigen Locus: Parkinson's Disease

This is a continuation of a possible series of blog posts all pertaining to the vast array of genetic content that the Human Leukocyte Antigen (HLA) locus has brought to the medical field. In a study conducted by the NeuroGenetics Research Consortium, led by a research scientist from the NY Department of Health and professors of genetics from several universities, pre-conclusive evidence was found that helped to link the immune system to the onset of the degenerative neurological disorder, Parkinson's disease.

The research team studied 2,000 Parkinson's patients and 2,000 clinical control volunteers, some for over two decades, in order to hone in on the most important data. Over that time, they were assessing the clinical, environmental and genetic factors that might contribute to the development of Parkinson's disease. The study was centralized on the HLA locus, which contributes to the majority of immune functions and responses in humans. Continuous study at this locus can help to reach conclusions on how infection, inflammation and autoimmunity may contribute to the onset of Parkinson's disease.



Although many important conclusions were made from this study, much more work in required to fully understand the correlation between the HLA locus and Parkinson's disease. The Consortium's next step is to look more into gene-environment links in order to personalize therapeutics for any specific individual.