Study identifies key factor in neural death that causes Parkinson's disease

Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia

April 27,2015

In studying the molecular biology of brain development, a team of researchers led by Ludwig Stockholm director Thomas Perlmann has discovered how disruption of a developmental mechanism alters the very nerve cells that are most affected in Parkinson's disease. They have also explained how such disruption induces a lethal dysfunction in the internal, house-keeping processes of such neurons. The results of their study, which took nearly four years to complete and involved the exquisitely targeted manipulation of mouse genes to generate a unique model of the disease, are published in the current issue of the journal Nature Neuroscience.

"Our model, in many important ways, mimics the manifestation of Parkinson's in humans and has illuminated what appears to be a key mechanism of neural decline in this devastating disease," says Perlmann.

An incurable neurological disorder, Parkinson's disease (PD) typically begins in patients as a mere tremor and progresses to a debilitating loss of control over movement and cognitive dysfunction, eventually leading to dementia and death. These symptoms are caused by the gradual wasting away of dopaminergic (DA) neurons, which respond to the neurotransmitter dopamine and are primarily clustered in the midbrain. They are critical to control of voluntary movement and the regulation of emotion.

The causes of their wholesale death in PD, however, remain something of a mystery. DA neurons of patients often contain odd clots of proteins named Lewy bodies. But it isn't clear whether these clumps cause neuronal death or are themselves an attempt by the cell to deal with a deeper dysfunction in breaking down and recycling the components of misfolded and malfunctioning proteins.

Perlmann and his colleagues were studying Lmx1a and Lmx1b, a pair of closely related transcription factors—proteins that control the expression of genes—involved in the development of DA neurons. These developmentally vital transcription factors persist even after the neurons have matured. To find out what they do in mature neurons, the researchers painstakingly engineered mice in a manner that permitted them to delete the Lmx1a/b genes in DA neurons alone, and to do so at a time of their choosing.

"When we looked at the DA neurons that lacked the Lmx1a/b genes, those in adult mice had many of the same abnormalities you see in various stages of PD," says Perlmann. "The nerve fibers that extend out from these neurons to others were degenerating, as were the nerve terminals, and this was happening long before the neurons died." Further, the engineered mice were shown in behavioral tests to have poor memory and motor control, both of which are symptoms of PD.

The researchers found that midbrain DA neurons from patients with PD express far lower levels of the Lmx1b protein than do their non-PD counterparts. So the researchers looked into how the loss of Lmx1a and b was affecting the neurons. They found that Lmx1b, in particular, controls the expression of a number of genes central to a process known as lysosomal autophagy by which cells break down abnormally folded protein molecules so that they don't poison the cell. This process is believed to be compromised in PD.

Treating young mice with a compound that boosts autophagy reversed the neural degeneration induced by loss of Lmx1b. In sum, the studies suggest the loss of Lmx1b expression is probably involved in the development of PD, that it induces a decline in the function of DA neurons by undermining autophagy and that this gradually sickens and then kills the DA neuron.

Perlmann and his colleagues are now using their unique animal model to research the details of Lmx1b's regulation of autophagy—such as the networks of genes it activates. The researchers are also looking into ways to prevent the loss of Lmx1b in PD and if such approaches could be of benefit in treating the disease. The process of autophagy also has relevance in cancer.

 Explore further: Mitochondria are altered in human cell model of Parkinson's disease

More information: Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease, Nature Neuroscience, DOI: 10.1038/nn.4004

http://medicalxpress.com/news/2015-04-key-factor-neural-death-parkinson.html

PAN Priority Remains in Updated Draft of 21st Century Cures

 April 29, 2015  Act4PD

On April 29, a bipartisan group of House Energy & Commerce Committee members released a second 21st Century Cures Initiative discussion draft.

The Parkinson’s Action Network (PAN) is excited that the draft includes the Advancing Research for Neurological Diseases Act, a provision that would create a data collection system for neurological diseases at the Centers for Disease Control and Prevention. The stand-alone bill (H.R. 292/S. 849), spearheaded in the House of Representatives by Reps. Burgess (R-TX) and Van Hollen (D-MD), is a top priority for the Parkinson’s’ community. Please show your continued support by urging your Members of Congress to support the Advancing Research for Neurological Diseases Act. Email today!

As you may recall, Chairman Upton (R-MI) released an initial draft of 21st Century Cures in January. On Thursday, April 30, the Health Subcommittee of the Energy & Commerce Committee will hold a hearing to discuss the updated draft.

The updated 21st Century Cures draft also includes provisions to:

• Increase funding for the National Institutes of Health;
• Incorporate the patient perspective in the discovery, development, and delivery process;
• Foster development of treatments for patients facing serious or life-threatening diseases; and
• Modernize clinical trials.

PAN staff is currently reviewing the entire draft and plans to continue working with the Committee as the process continues. Please stay tuned for updates

Go to: (To Read More)

http://parkinsonsaction.org/wp-content/uploads/2014/10/PAN-2.23.15-Senate-HELP.pdf

http://parkinsonsaction.org/pan-priority-remains-in-updated-draft-of-21st-century-cures/

A Parkinson's Diagnosis at Any Age Has Unique Challenges

Resources for Individuals and Physicians Offer Advice From Those Who've Been There 

TORONTO, ON--(Marketwired - April 29, 2015) - Learning you've got Parkinson's disease, a chronic neurodegenerative condition, when you're not yet 30 years old, can be a shocking and very emotional experience. Even at 50, it can wreak havoc on your future plans -- physically, mentally, financially, socially and emotionally. Parkinson Society Canada has funded two educational resources -- one for patients and one for physicians -- to help address the unique needs of individuals who are newly diagnosed with Young-onset Parkinson's disease (YOPD), developed by a National Research Program grant recipient. 

Although the average age to develop Parkinson's is around 60, young-onset Parkinson's (before age 40) occurs in five to 10 per cent of people diagnosed. Twenty percent of those newly diagnosed are under the age of 50. Some challenges in living with Parkinson's disease are universal, regardless of age, and there are a number of additional issues specific to younger people. 

The first is often the shock of a diagnosis of YOPD. "I think when you get the diagnosis, your life sort of stops," recalls one of the contributors to the booklet on advice for other patients. "You have to deal with your kids, you have to deal with your job, you have to deal with getting up every day and all the things you're supposed to do and then deal with this at the same time. And there's no instruction book on how to do that."

These latest resources help to fill that gap. Written by Michael Ravenek, PhD and associate professor at Western University, the two booklets, Young-onset Parkinson's disease: Advice for those newly diagnosed from individuals currently living with YOPD (2nd ed.) and Young-onset Parkinson's disease: Advice for physicians from individuals living with YOPD (2nd ed.) provide advice on personal topics such as when to reveal your condition to your employer, planning finances for possible disability or early retirement, sharing your diagnosis with young children, teenagers and parents, and sexuality, among several others issues.

With funding from Parkinson Society Canada and the Canadian Institutes of Health Research, Ravenek interviewed 39 people living with YOPD to write the initial editions of the two booklets. Feedback was later gathered from across the country from others with YOPD and their families, as well as health professionals to inform the second editions.

Helping those with young-onset Parkinson's disease 

"There is a big gap in information available to those who face everyday life challenges combined with the unexpected and unique aspects of living with YOPD.' says Grace Ferrari, National Manager, Professional & Public Education, Parkinson Society Canada. "We are very pleased to provide these additional resources in both digital and printed formats, in English and French, to support families, people with Parkinson's and their physicians."

The physician booklet highlights specific areas of the physician-patient interaction that all physicians should consider in their encounters with individuals with YOPD. Both booklets contain a sample "log" for daily medication, meals and exercise, along with a place to record "Questions for my next doctor's appointment," to help make the most of self-care efforts and doctor/patient interactions, respectively.

To find out more about living with Parkinson's disease and programs and services available near you, call 1-800-565-3000 or visit www.parkinson.ca. Use the interactive mapto find support groups, access to local programs and support groups for newly diagnosed, Young-Onset, exercise and more. Join the conversation on Twitter @ParkinsonCanada and follow Parkinson Society Canada on Facebook.

http://health.einnews.com/article/262631684/Z62GdZgmGBEYzaTv

Molecular Medical Food for Parkinson's Disease Produces 80% Improvement on all Symptoms Based on a Case Study Involving a Parkinson's Patient

BELMONT, Calif., April 29, 2015 (GLOBE NEWSWIRE) 

-- via PRWEB -

Xicepta Sciences, Inc., a biotech company in Belmont, CA, launches a molecular medical food, Agitan X, for Parkinson's disease that produces 80% improvement on all symptoms based on the company's case study involving a Parkinson's disease patient. Agitan X contains embryonic peptides from vaccine-grade chicken egg extract with microRNA nucleotides and peptides that replenishes what the disease has depleted in the sufferer's body. It also contains other natural ingredients including Amino Acids and Dopamine properties.

The core research and biotechnology of the embryonic peptide was developed by Dr. Gheorghe Mihaescu, an international expert in the fields of Experimental Immunology in Oncology, Steroid Biochemistry, Radio-assay Methodologies, and Geriatric Nutrition. Dr. Mihaescu has authored 32 published scientific papers in the aforementioned fields and has also performed human clinical studies on the benefits of the embryonic peptides. He also holds 15 invention patents, which have been recognized and prized by the European scientific community at the prestigious Brussels and Geneva Conventions.

The effectiveness of Agitan X in alleviating the disease's symptoms can be attributed to the neuroregenerative function of the factors and the miRNA strands that can be found in the embryonic peptides. These factors cross easily and intact from digestion in the large intestine to the blood stream where they interact and contribute to the renewal of the neural cell life cycle. The rest of the products' natural ingredients are designed to enhance the effectiveness of Agitan X.

Research shows that Parkinson's disease results from lack of dopamine and the degeneration of brain neurons. The symptoms include among others tremors, physical imbalance, muscle rigidity, drooling, and loss of energy. Overtime patients may also exhibit dementia-like symptoms and depression. All of Agitan X's ingredients are formulated to address the disease's symptoms as well as induce cell and tissue repair.

In a case study conducted by Xicepta Sciences, Agitan X was given to Patient A who suffered from Parkinson's disease for over eight years and has degenerated into what may be considered at the last stage of the disease. He exhibited symptoms such as extreme tremors, stuttering, gait imbalance, forgetfulness, depression and has in fact entertained suicidal ideation. Within 30 days after taking Agitan X , Patient A exhibited significant improvement in all areas of Parkinson's disease's core symptoms. After another 45 days, Patient A has gained approximately 80% improvement in all diagnostic axis. Patient A also reported that he now sleeps better, is in much happier mood, has gained back his normal gait and musculature, and even resumed riding his Harley Davidson motorcycle.

Xicepta Sciences is a founder-funded company and it is currently seeking an A-Round funding in order to perform additional studies and bring the product to the global market. Xicepta Sciences owns the exclusive rights to the trade and use of the patented embryonic peptide technology which took over 10 years to test and perfect. Agitan X is available for sale at xicepta.com.

For more information or to schedule an interview regarding the topic, please contact Dr. Soledad M. Manaay, President and CEO of Xicepta Sciences, Inc. at 650-771-7676 or at dr(dot)manaay(at)xicepta(dot)com.

This article was originally distributed on PRWeb. For the original version including any supplementary images or video, visit http://www.prweb.com/releases/2015/04/prweb12681294.htm

http://health.einnews.com/article/262611397/LxxkTlUmMaBcXQWc

Immune gene variant magnifies Parkinson's risk from insecticide exposure

Pyrethroids are found in the majority of commercial household insecticides. Although they are neurotoxic for insects, exposure to them is generally considered safe for humans by federal authorities. Image from Thinkstock.

Woodruff Health Sciences Center | April 27, 2015

Genetic variation and exposure to pesticides both appear to affect risk for Parkinson's disease. A new study has found a connection between these two risk factors, in a way that highlights a role for immune responses in progression of the disease.

The results are published in the inaugural issue of NPJ Parkinson's Disease.

The findings implicate a type of pesticide called pyrethroids, which are found in the majority of commercial household insecticides, and are being used more in agriculture as other insecticides are being phased out. Although pyrethroids are neurotoxic for insects, exposure to them is generally considered safe for humans by federal authorities.

The study is the first making the connection between pyrethroid exposure and genetic risk for Parkinson's, and thus needs follow-up investigation, says co-senior author Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine.

The genetic variation the team probed, which has been previously tied to Parkinson's in larger genome-wide association studies, was in a non-coding region of a MHC II (major histocompatibility complex class II) gene, part of a group of genes that regulate the immune system.

"We did not expect to find a specific association with pyrethroids," Tansey says. "It was known that acute exposure to pyrethroids could lead to immune dysfunction, and that the molecules they act on can be found in immune cells; now we need to know more about how longer-term exposure affects the immune system in a way that increases risk for Parkinson's."

"There is already ample evidence that brain inflammation or an overactive immune system can drive the progression of Parkinson's. What we think may be happening here is that environmental exposures may be altering some people's immune responses, in a way that promotes chronic inflammation in the brain."

For this study, Emory investigators led by Tansey and Jeremy Boss, PhD, chair of microbiology and immunology, teamed up with Stewart Factor, DO, head of Emory's Comprehensive Parkinson's Disease Center, and public health researchers from UCLA led by Beate Ritz, MD, PhD. The first author of the paper is MD/PhD student George T. Kannarkat.

The UCLA researchers used a California state geographical database covering 30 years of pesticide use in agriculture. They defined exposure based on proximity (someone's work and home addresses), but did not measure levels of pesticides in the body. Pyrethroids are thought to decay relatively quickly, especially in sunlight, with half-lives in soil of days to weeks.

In a group of 962 people from California's Central Valley, a common MHC II variant combined with above-average exposure to pyrethroid pesticides to increase the risk of Parkinson's disease. The riskiest form of the gene (where an individual is carrying two risk alleles) was found in 21 percent of Parkinson's patients and 16 percent of controls.

In this group, genes or pyrethroid exposure by themselves did not significantly increase Parkinson's risk, but together, they did. People with more-than-average exposure to pyrethroids and carrying the riskiest form of the MHC II gene had 2.48 times more risk for Parkinson's than less-exposed people with the least risky gene form. Exposure to other types of pesticides such as organophosphates or paraquat did not heighten risk in the same way.

Larger genetic studies (some including Factor and his patients) have previously identified variations in MHC II genes as having connections to Parkinson's. Puzzlingly, the same genetic variants affect Parkinson's risk differently in Caucasian/European and Chinese populations. MHC II genes are highly variable between individual humans; that's why they play a big role in organ transplant matching.

Other experiments showed that the genetic variant connected to Parkinson's is connected with immune cell function. In a group of 81 Parkinson's patients and control participants from Emory of European ancestry the immune cells from people who had the higher-risk MHC II gene variant studied in California displayed more MHC molecules on their surfaces, the researchers found.

MHC molecules are central to the process of "antigen presentation," a driver for T cells to become activated and have the rest of the immune system get involved. Heightened expression of MHC II was present in resting cells from both Parkinson's patients and healthy controls; but greater responsiveness to immune challenges were observed in Parkinson's patients with the higher risk genotype.

The authors conclude: "Our data suggest that cellular biomarkers (like MHC II activation) may prove more useful than soluble molecules in plasma and cerebrospinal fluid to identify individuals at risk for disease or for patient recruitment into neuroprotective trials testing immunomodulatory drugs."

The research was supported by the National Institute for Neurological Disorders and Stroke (R01NS072467, 1P50NS071669, F31NS081830), the National Institute of Environmental Health Sciences (5P01ES016731), the National Institute of General Medical Sciences (GM47310), the Sartain Lanier Family Foundation and the Michael J. Fox Foundation for Parkinson's Research.

http://news.emory.edu/stories/2015/04/immune_gene_pesticide_parkinsons/index.html?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+NewswoodruffHealthSciencesCenter+%28Woodruff+Health+Sciences+Center%3A+Emory+News+Center+%28formerlyNews%40Woodruff+Health+Sciences+Center%29%29

A glitch in the recycling: Study identifies key factor in the neural death that causes Parkinson's disease

  

In studying the molecular biology of brain development, a team of researchers led by Ludwig Stockholm director Thomas Perlmann has discovered how disruption of a developmental mechanism alters the very nerve cells that are most affected in Parkinson's disease. They have also explained how such disruption induces a lethal dysfunction in the internal, house-keeping processes of such neurons. The results of their study, which took nearly four years to complete and involved the exquisitely targeted manipulation of mouse genes to generate a unique model of the disease, are published in the current issue of the journal Nature Neuroscience.

"Our model, in many important ways, mimics the manifestation of Parkinson's in humans and has illuminated what appears to be a key mechanism of neural decline in this devastating disease," says Perlmann.

An incurable neurological disorder, Parkinson's disease (PD) typically begins in patients as a mere tremor and progresses to a debilitating loss of control over movement and cognitive dysfunction, eventually leading to dementia and death. These symptoms are caused by the gradual wasting away of dopaminergic (DA) neurons, which respond to the neurotransmitter dopamine and are primarily clustered in the midbrain. They are critical to control of voluntary movement and the regulation of emotion.

The causes of their wholesale death in PD, however, remain something of a mystery. DA neurons of patients often contain odd clots of proteins named Lewy bodies. But it isn't clear whether these clumps cause neuronal death or are themselves an attempt by the cell to deal with a deeper dysfunction in breaking down and recycling the components of misfolded and malfunctioning proteins.

Perlmann and his colleagues were studying Lmx1a and Lmx1b, a pair of closely related transcription factors--proteins that control the expression of genes--involved in the development of DA neurons. These developmentally vital transcription factors persist even after the neurons have matured. To find out what they do in mature neurons, the researchers painstakingly engineered mice in a manner that permitted them to delete the Lmx1a/b genes in DA neurons alone, and to do so at a time of their choosing.

"When we looked at the DA neurons that lacked the Lmx1a/b genes, those in adult mice had many of the same abnormalities you see in various stages of PD," says Perlmann. "The nerve fibers that extend out from these neurons to others were degenerating, as were the nerve terminals, and this was happening long before the neurons died." Further, the engineered mice were shown in behavioral tests to have poor memory and motor control, both of which are symptoms of PD.

The researchers found that midbrain DA neurons from patients with PD express far lower levels of the Lmx1b protein than do their non-PD counterparts. So the researchers looked into how the loss of Lmx1a and b was affecting the neurons. They found that Lmx1b, in particular, controls the expression of a number of genes central to a process known as lysosomal autophagy by which cells break down abnormally folded protein molecules so that they don't poison the cell. This process is believed to be compromised in PD.

Treating young mice with a compound that boosts autophagy reversed the neural degeneration induced by loss of Lmx1b. In sum, the studies suggest the loss of Lmx1b expression is probably involved in the development of PD, that it induces a decline in the function of DA neurons by undermining autophagy and that this gradually sickens and then kills the DA neuron.

Perlmann and his colleagues are now using their unique animal model to research the details of Lmx1b's regulation of autophagy--such as the networks of genes it activates. The researchers are also looking into ways to prevent the loss of Lmx1b in PD and if such approaches could be of benefit in treating the disease. The process of autophagy also has relevance in cancer.

http://health.einnews.com/article/262471565/jNQTJhAsQRh1mu_R

Kirk Gibson has been diagnosed with Parkinson's disease

DETROIT (AP) - 

Kirk Gibson

April 28 2015 

The 1988 National League MVP was fired in September as manager of the Arizona Diamondbacks after four-plus seasons. He now calls Tigers games for Fox Sports Detroit, but Gibson had not been in the broadcast booth since opening day April 6 while undergoing tests.

"I have faced many different obstacles in my life, and have always maintained a strong belief that no matter the circumstances, I could overcome those obstacles," he said in a statement through the network. "While this diagnosis poses a new kind of challenge for me, I intend to stay true to my beliefs. With the support of my family and friends, I will meet this challenge with the same determination and unwavering intensity that I have displayed in all of my endeavors in life. I look forward to being back at the ballpark as soon as possible."

The 57-year-old Gibson had one of the most memorable moments in baseball history with his limping, pinch-hit home run in the ninth inning of Game 1 of the 1988 World Series for the Dodgers. He also won a championship in 1984 with the Tigers, where he played 12 of his 17 major league seasons.

Copyright 2015 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

http://health.einnews.com/article/262484998/3syGkQCvSsIIqoh0

Favorite Walk Moments from the 21st Parkinson's Unity Walk #puw2015

Parkinson's sufferers 'feel like zoo exhibits' due to rudeness and hostility from the public

HELL: Susan Harbot of Horwich has has spoken out about living with Parkinson's Disease. 

by Tui Benjamin, Reporter

RUDENESS and hostility is making Parkinson’s sufferers “feel like zoo exhibits” when they leave their homes.

Horwich mother-of-four Susan Harbot said she has been forced to develop a tough skin to deal with misunderstanding of the condition.

The widowed 65-year-old has spoken out about the public humiliation she has been subjected to since her diagnosis nine years ago at the age of 56.

Parkinson’s UK research last week revealed more than half of sufferers in the North West say they have experienced hostility and rudeness

One in three sufferers have been stared at, a quarter have been mistaken for being drunk and 10 per cent have been laughed at in the street.

Mrs Harbot said: “I was getting up from a disabled seat on the bus, wearing my badge that states l have Parkinson’s, when a gentleman asked me if my badge was a reason or excuse for sitting in the disabled seat as ‘clearly there was nothing wrong with me’.

“The feeling of being completely misjudged stayed with me all day, it was horrible. I think the negative reactions upset my family more than they do me now.

“I have developed a tough skin over the years. I just wish people would show some common courtesy. Parkinson’s isn’t a reason or an excuse, it’s just what I have got.”

Parkinson’s – a progressive neurological condition – has no cure and the symptoms get worse over time.

The disease was responsible for the death of Mrs Harbot’s mother, Constance, when she was in her seventies and her two brothers Paul and David were diagnosed at 63 and 58.

Two years ago she was fitted with a brain stimulator to reduce her tremors, but this will not stop the degenerative illness from accelerating.

Mrs Harbot added: “I don’t think the public realise there are other symptoms than shakes – Parkinson’s takes a piece of your life.

“Slowness is another big symptom, as is fatigue. I have been asked if I can move any quicker. If I shake a lot of people get up and move away.

“My four daughters are fantastic, and it is horrible to know Parkinson’s could affect them. There is no known test for it.”

Parkinson’s affects 127,000 people in the UK and an estimated 14,000 in the North West – nearly two thirds of whom suffer from anxiety because of their condition.

Almost one in five of sufferers in the region said the fear of humiliation and negative reactions makes them feel trapped in their homes.

Professor David Burn, Parkinson’s UK clinical director and consultant neurologist, said: “It is devastating to see the added burden thoughtless reactions from the public are having on people with Parkinson’s.

“Patients I see in the clinic are already battling a myriad of neurological symptoms including anxiety, depression and insomnia.

“The last thing they need is to feel like a zoo exhibit when they step out of their front door.”

Parkinson’s UK has launched a campaign to urge the public to show kindness to people with Parkinson’s. For more information: go to upyourfriendly.com

http://health.einnews.com/article/262228705/bQgedwyslAttmJDK

Hopes of vaccine for Parkinson’s sufferers

Research hints that disease is caused by toxins, whose spread to the brain could be blocked

Scientists have raised hopes that they may be able to create a vaccine to block the progress of Parkinson’s disease.

They believe new research provides evidence that an abnormal protein may trigger the condition. If the theory is correct, researchers say it might be possible to prime a person’s immune system – using a special vaccine – so it is ready to attack the rogue protein as it passes through the body. In this way, the protein would be prevented from destroying a person’s dopamine-manufacturing cells, where the disease inflicts its greatest damage.

This new vision of Parkinson’s has been arousing excitement among researchers. “It has transformed the way we see Parkinson’s,” said Roger Barker, professor of clinical neurosciences at Cambridge University.

Parkinson’s does not usually affect people until they are over 50. However, researchers have uncovered recent evidence that suggests it may be caused by an event occurring 10 to 20 years before its main symptoms – tremors, rigidity and slowness of movement – manifest themselves.

“If you ask Parkinson’s patients if, in the past, they have experienced loss of sense of smell or suffer from disturbed sleep or have problems with their bowels, very often they reply they have,” said Barker, whose work is backed by the charity Parkinson’s UK, whose Parkinson Awareness week ends on Sunday. “Frequently these patients manifest symptoms several years before it becomes apparent they have the disease. We now believe there is a link.”

Barker and many other researchers say toxins get taken up in the bowels of patients and that over the years these are slowly transported to the central nervous system until they become lodged in some of the cells of the brain. There, they ultimately wreak damage to cells of the mid-brain, where dopamine, a neurotransmitter involved in motor control, is made.However, this raises a key question: what is the nature of the toxin? “There is growing evidence to suggest that it is a normal protein that has become altered in shape and this abnormal version causes other proteins of the same type to change their shape as well,” said Barker. “Such abnormal proteins are known as a prions, and we think one of them is critically involved in the development of Parkinson’s.”

Prions were first proposed to be the causes of fatal brain diseases such as Creutzfeldt-Jakob in the 1980s, and have since been linked to a number of conditions affecting humans and animals. The connection between prion-like proteins and Parkinson’s is of relatively recent origin, however.

“Prions are abnormal versions of a normal protein,” said Barker. “They spread by transforming normal proteins with which they come into contact into abnormal versions.” Again, recent evidence suggests this may occur in the brains of Parkinson’s patients. Several attempts were made to transplant brain cells taken from aborted foetuses into the brains of people with Parkinson’s. These foetal cells should have restored the abilities of these patients to make dopamine, and although they did so in some cases, it also became clear that some transplanted dopamine cells developed the pathology of Parkinson’s. “That suggests an agent in patients’ brains spread to the foetal cells and affected them as well,” said Barker.

As to the identity of the protein transformed in Parkinson’s, the main candidate is alpha-synuclein, which is found in the brain, though its function is unclear. Recent research suggests it could be transformed into an abnormal state and play a key role in development of Parkinson’s. More importantly, it is possible that its operations could be blocked by devising vaccines to interrupt its spread through the body and so protect the brain’s dopamine production.

“It is early days, though at least one company – in Austria – has already begun trials,” says Barker. “We are probably many years from such a vaccine for Parkinson’s, but there is no doubt about the level of excitement in the field today.”

http://www.theguardian.com/society/2015/apr/25/parkinsons-disease-vaccine-research-protein?CMP=share_btn_fb