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I copy news articles pertaining to research, news and information for Parkinson's disease, Dementia, the Brain, Depression and Parkinson's with Dystonia. I also post about Fundraising for Parkinson's disease and events. I try to be up-to-date as possible. I have Parkinson's
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Saturday, April 12, 2014

Your Symptoms are Unique to You

Your Symptoms are Unique to You

How to Cope With the Symptoms of Parkinson's Disease

"The only predictable thing about this disease is that it is unpredictable."
- Richard, diagnosed at 36
Tremors are the first sign noted in about half of all people with Parkinson's disease. But maybe, like 15 percent of people with the illness, you have never experienced this symptom. That is because Parkinson's disease affects everyone somewhat differently.
As you will discover, your symptoms will continue to change, often from day to day, and throughout the course of your life. But even though there is no cure for Parkinson's, the sooner you can take steps to manage symptoms when they arise, the better chance you will have at maintaining a good quality of life.
That is why the first step in coping with the changes that accompany a Parkinson's diagnosis is to simply increase awareness, to notice new symptoms as well as how your body responds to certain activities, stresses and therapies. A helpful way to do this is by logging your symptom patterns in a daily journal. It is just a matter of jotting down small changes you notice in your physical and emotional health each day. That way you can discuss these issues promptly with your doctor and receive treatment.

Do What You Can While You Can

"I have had Parkinson's disease for nearly 20 years. My wife is a teacher, so we travel every summer when she is not working. Since my diagnosis, I have been to China, Nepal, Prague, Paris and many other places. The Parkinson's comes along, too, so our trips require more planning than they used to and we involve my care team. We factor in daily naps and take it slow. My balance isn't as good as it used to be and too much walking wears me out so we bring a collapsible wheelchair along or make sure one is available. I also use a cane. I don't know how many more places we will get to visit as my disease continues to progress, but we have made some wonderful memories that we wouldn't have if we had let my Parkinson's dictate every aspect of our lives."
- Nicholas, diagnosed at 52, still traveling at 72
Many people with Parkinson's disease are not allowing the condition to take over their lives. Despite the everyday setbacks they face, they are still creating fulfilling lives for themselves by redirecting their attention to people and activities that bring them joy. You can do the same. Try building a few hobbies into your routine that will give you a break from dwelling on the disease. Find some activities that help you forget about Parkinson's for a while. That may be painting, writing, gardening, or reading to your grandchildren.

Ask for Help

Whether you were diagnosed early in the disease, or have had symptoms for quite some time, there will come a day when you can no longer do something. That may involve carrying a cup of coffee or being able to write down a phone number while you talk on the telephone.
Although asking for help with activities of daily living (ADLs) can be very difficult, particularly if you have never been one to rely on others, you will need to learn how to request and accept assistance as your disease progresses. Drawing from the care and interactions of close friends and family will help you cope better with the illness.

Accept What You Can No Longer Do

Over time, it may seem as though you are losing your independence because you can no longer do all the things you once did. As these losses occur, you will probably go through the five stages of grief identified by Dr. Elisabeth Kübler-Ross. They include denial, anger, bargaining, depression and acceptance. Being aware of the issue or loss to which you are reacting will help you to move from one stage to another more easily.
No matter what your symptoms are, motor or non-motor symptoms, don't let Parkinson's beat you!

The Michael J. Fox Foundation for Parkinson's Research

4 hrs · 
Are you of Eastern European Jewish ancestry, and either have Parkinson’s disease or a family member with the disease?
If so, you may qualify for genetic testing at no cost for an important study investigating the link between Parkinson’s disease and genetics.
Learn more:
Over the past decade, studies of the genetics of Parkinson’s disease have revolutionized the pursuit of a “disease-modifying” treatment — a therapy that can slow or stop the progression of PD.

Parkinson's Disease and Pesticides: What's the Connection?

Scientists find a way chemicals may contribute to Parkinson’s

The pesticide Parkinson's connection

What exactly causes Parkinson’s disease is far from figured out. But a clue has been lurking in cornfields for years.

The data confirm it: farmers are more prone to Parkinson’s than the general population. And pesticides could be to blame. Over a decade of evidence shows a clear association between pesticide exposure and a higher risk for the second most common neurodegenerative disease, after Alzheimer's. A new study published inNeurology proposes a potential mechanism by which at least some pesticides might contribute to Parkinson’s.

Regardless of inciting factors — and there appear to be many — Parkinson’s ultimately claims dopamine-releasing neurons in a small, central arc of brain called the “substantia nigra pars compacta.” The nigra normally supplies dopamine to the neighboring striatum to help coordinate movement. Through a series of complex connections, striatal signals then find their way to the motor cortex and voila, we move. But when nigral neurons die, motor function goes haywire and the classic symptoms set in, including namely tremors, slowed movements, and rigidity.

Pesticides first came under suspicion as potentially lethal to the nigra in the early 1980s following a tragic designer drug debacle straight out of Breaking Bad. Patients started showing up at Northern California ERs nearly unresponsive, rigid, and tremoring — in other words, severely Parkinsonian. Savvy detective work by neurologist Dr. William Langston and his colleagues, along with the Santa Clara County police, traced the mysterious outbreak to a rogue chemist and a bad batch. He’d been trying to synthesize a “synthetic heroin” — not the snow cone flavorings he claimed — however a powder sample from his garage lab contained traces of an impurity called MPTP. MPTP, it turned out, ravages dopaminergic neurons in the nigra and causes what looks like advanced Parkinson’s. All of the newly Parkinsonian patients were heroin users who had injected the tainted product. And MPTP, it also turned out, is awfully similar in structure to the widely used herbicide paraquat, leading some neurologists to turn their attention to farms and fields.

In 2000, a meta-analysis linked confirmed and presumed pesticide exposure with increased risk of Parkinson’s. Subsequent work supported this connection, including a large 2006 study that followed patients for nine years. The patients exposed to pesticides had a 70% higher incidence of Parkinson’s when the study ended; the risk was the same for exposed farmers and exposed non-farmers, hence some other farm-related factor wasn’t to blame. The study didn’t report on specific toxins, but more recent work out of The Parkinson’s Institute in Sunnyvale, CA, founded by Langston after the MPTP discovery, did. The authors took detailed occupational and exposure histories from farmers and their families. Paraquat upped Parkinson’s risk 2.5-fold. Rotenone was also red-flagged.

Pesticides exert their neurotoxicity in a number of ways. Both paraquat and rotenone appear to wither dopaminergic neurons via free radical productionFree radicals are atoms or molecules with an unpaired electron looking for a partner; they do major cellular damage by pilfering electrons from other molecules, impairing their function. Rotenone may also interfere with the normal neuronal clearance of damaged or degraded proteins. Faulty proteins accumulate, derailing various cellular processes.

The new study, from a team at UCLA, proposes yet another mechanism by which some pesticides might contribute to Parkinson’s. It might also provide a major lead in understanding the disease. The team had previously found that the fungicide benomyl was associated with increased Parkinson’s risk and damaged the brain by inhibiting an enzyme called ALDH that normally helps metabolize fats, proteins and toxins like alcohol (certain ALDH mutation carriers have to take it easy at the bar). ALDH also detoxifies the dopamine metabolite DOPAL. When the enzyme isn’t working properly, DOPAL builds up in neurons and may explain the loss of dopaminergic neurons in Parkinson’s. This time around the authors tested 26 pesticides, first for their influence on ALDH activity in rat neurons and next for any epidemiologic association with Parkinson’s. Eleven pesticides inhibited ALDH at the concentration tested, eight of which could be included in the study based on available histories from 360 rural Californian patients. All eight were associated with an increased Parkinson’s risk and genetic variation in the ALDH2 subtype of the enzyme increased the risk further in those exposed. The findings not only point to new culprit compounds, but reflect the growing appreciation of Parkinson’s as a multifactorial disease, in many cases due to the collusion of both genetic and environmental factors.

At least 10% of Parkinson’cases are now thought to be due primarily to specific gene variants, and estimates suggest that genetics may contribute to upwards of 20% to 50%. Patients with a few specific mutations — common in people of Mediterranean descent — carry a nearly 100% chance of developing the disease. Though, as lead author Dr. Jeff M. Brontstein commented to Scientific American, while a minority of cases might be primarily due to a specific genetic or environmental risk factor, ultimately many if not most cases are likely due to gene-environment interactions. This may explain why there isn’t an epidemic of Parkinson’s in rural areas. Despite the large number of people regularly exposed to pesticides, not everyone has a genetic susceptibility.

This gets incredibly complicated when you consider the possibility of multiple genetic and environmental risk factors working together. It's clear that pesticides wreak havoc on the brain through a variety of mechanisms. Hence farmers and others regularly exposed are at risk for a multipronged, possibly cumulative attack. Certain industrial solvents also appear to bump up Parkinson’s vulnerability. Head trauma, in combination with a particular mutation, does too. And diets high in omega-3 fatty acids, found in fish, plant and seed oils, appear to protect against the disease. The laundry list of risk factors and contributors could explain the varied symptoms experienced by Parkinson’s patients. Some present early in life, some late. For many the classic motor symptoms predominate; others present with non-motor findings like sleep disturbances, constipation and depression. No two cases are identical.

The confusion isn’t just clinical. Recent evidence positions Parkinson’s as one of a number of related neurodegenerative disorders marked by the accumulation of abnormal proteins in the brain, including Alzheimer’s disease and ALS. They all appear partially genetic, partially environmental and probably in many cases both. Neuronal protein accumulations called Lewy bodies — a pathologic hallmark of Parkinson’s — are also found in the brains of Alzheimer’s patients; PD-afflicted brains often contain the amyloid protein aggregates common to Alzheimer’s. It’s a Venn diagram of neurodegeneration.

The new findings further confirm that those whose livelihood relies on repelling pests should pay mind to their increased risk for Parkinson’s, particularly if they have other known risk factors, and take precautions. They can limit exposure and avoid the riskier compounds. They can wear masks, clean up spills and wash up vigorously. Moreover, implicating ALDH in Parkinson’s pathology could represent an important step toward determining a final common pathway on which the various risk factors converge, a potential holy grail for drug development, and ultimately for patients. Rarely are neurologic diseases straight forward, and Parkinson’s has proved no different. But a terribly unfortunate outcome for many in search of heartier, healthier crops may have brought medicine one notch closer to deciphering a frustratingly complex disease.

Are you a scientist who specializes in neuroscience, cognitive science, or psychology? And have you read a recent peer-reviewed paper that you would like to write about? Please send suggestions to Mind Matters editor Gareth Cook, a Pulitzer prize-winning journalist and regular contributor to Gareth is also the series editor of Best American Infographics, and can be reached at garethideas AT or Twitter @garethideas.

Fighting Parkinson's with the power of dance

by Kate Haggman
Fighting Parkinson’s with the power of dance
Professors Gene Moyle and Graham Kerr are part of the research team working with Queensland Ballet on the Dance for Parkinson's program.
Brisbane researchers are measuring the power of dance for a special group of Queenslanders.
Dance and health academics from QUT and The University of Queensland are working with Queensland Ballet and Parkinson's Queensland on a  that aims to improve both the health and wellbeing of people affected by the neurological disease.
Queensland Ballet's Dance for Parkinson's pilot program offers free  workshops in its West End studios for people with Parkinson's disease and their carers, facilitated by Dance for Parkinson's specialist Erica Rose Jeffrey.
But it's much more than just an exercise class.
"Dance for Parkinson's welcomes people affected by Parkinson's into the Queensland Ballet family - they're in the studios interacting with the professional dancers, learning parts of the company's repertoire, watching the professionals' daily ballet classes, seeing the dress rehearsals," said Associate Professor Gene Moyle, head of QUT Creative Industries' dance discipline.
"That strong social interaction with the Queensland Ballet community is a really important factor in promoting long-term happiness and emotional fulfilment in a group of people who are managing the burden of a degenerative condition.
"One of the effects of Parkinson's is a steady reduction in brain function, which can lead to depression, lethargy and apathy.
"The strong bonds Dance for Parkinson's participants forge within this supportive community can make all the difference to their mental health - and learning to express themselves creatively can be a fantastic mood enhancer."
Queensland Ballet CEO Anna Marsden said her Company was passionate about celebrating the health and fitness benefits of ballet with the community and was proud to introduce Dance for Parkinson's to Queensland.
"This innovative program, the first Dance for Parkinson's program offered by a professional dance company in Australia, is a great example of how arts and science can work together to improve the lives of those affected by Parkinson's."
Queensland Ballet's pilot program is based on a similar New York program developed by David Leventhal and the Mark Morris Dance Group.
Prior international research suggests that, as well as positive impacts on quality of life, dance can also improve cognitive performance and reaction times, making it a useful means of alleviating symptoms for a number of conditions, including arthritis, dementia, depression and Parkinson's.
The Queensland researchers will rigorously assess the physical health, social, emotional and psychological benefits of Queensland Ballet's program.
The research is voluntary among participants and care givers, and involves clinical measurements, questionnaires, personal interviews, observational filming and journal reflections.
Neuroscientist with QUT's Institute of Health and Biomedical Innovation Professor Graham Kerr said combining cardio with strategy, coordination and rhythm may be particularly helpful for people with Parkinson's, whose neural pathways have degenerated, making it increasingly difficult for the brain to transmit signals to the body.
"Parkinson's has a profound effect on movement so anything we can do to improve their flexibility, balance and coordination will be beneficial," said Professor Kerr, who is also the Vice President of Parkinson's Queensland.
"People with Parkinson's typically become quite stiff and rigid. The risk of falling over and being severely injured is very high. Fractured skulls and hips are quite common.
"Our study will measure exactly how much the exercise delivered through Dance for Parkinson's improves balance, walking and coordination as well as quality of life and well-being."
The findings of the research are expected to be released later this year.

Too much protein may kill brain cells as Parkinson's progresses

Too much protein may kill brain cells as Parkinson's progresses
NIH-funded scientists show that the deadly Parkinson's gene LRRK2 can kill nerve cells (green) by tagging the s15 ribosomal protein (purple), a cog in a cell's protein-making machinery. Credit: Dawson lab, JHU Morris K. Udall Center of Excellence for Parkinson's Disease.
Scientists may have discovered how the most common genetic cause of Parkinson's disease destroys brain cells and devastates many patients worldwide. The study was partially funded by the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS); the results may help scientists develop new therapies.
"This may be a major discovery for Parkinson's disease patients," said Ted Dawson, M.D., Ph.D., director of the Johns Hopkins University (JHU) Morris K. Udall Center of Excellence for Parkinson's Disease, Baltimore, MD. Dr. Dawson and his wife Valina Dawson, Ph.D., director of the JHU Stem Cell and Neurodegeneration Programs at the Institute for Cell Engineering, led the study published inCell.
The investigators found that mutations in a gene called leucine-rich repeat kinase 2 (LRRK2; pronounced "lark two" or "lurk two") may increase the rate at which LRRK2 tags ribosomal proteins, which are key components of protein-making machinery inside cells. This could cause the machinery to manufacture too many proteins, leading to .
"For nearly a decade, scientists have been trying to figure out how mutations in LRRK2 cause Parkinson's disease," said Margaret Sutherland, Ph.D., a program director at NINDS. "This study represents a clear link between LRRK2 and a pathogenic mechanism linked to Parkinson's disease."
Affecting more than half a million people in the United States, Parkinson's disease is a degenerative disorder that attacks nerve cells in many parts of the nervous system, most notably in a brain region called the substantia nigra, which releases dopamine, a chemical messenger important for movement. Initially, Parkinson's disease causes uncontrolled movements; including trembling of the hands, arms, or legs. As the disease gradually worsens, patients lose ability to walk, talk or complete simple tasks.
For the majority of cases of Parkinson's disease, a cause remains unknown. Mutations in the LRRK2 gene are a leading genetic cause. They have been implicated in as many as 10 percent of inherited forms of the disease and in about 4 percent of patients who have no family history. One study showed that the most common LRRK2 mutation, called G2019S, may be the cause of 30-40 percent of all Parkinson's cases in people of North African Arabic descent.
LRRK2 is a kinase enzyme, a type of protein found in cells that tags molecules with chemicals called phosphate groups. The process of phosphorylation helps regulate basic nerve cell function and health. Previous studies suggest that disease-causing mutations, like the G2019S mutation, increase the rate at which LRRK2 tags molecules. Identifying the molecules that LRRK2 tags provides clues as to how nerve cells may die during Parkinson's disease.
In this study, the researchers used LRRK2 as bait to fish out the proteins that it normally tags. Multiple experiments performed on  suggested that LRRK2 tags ribosomal proteins. These proteins combine with other molecules, called ribonucleic acids, to form ribosomes, which are the cell's protein-making factories.
Further experiments suggested that disease-causing mutations in LRRK2 increase the rate at which it tags two ribosomal proteins, called s11 and s15. Moreover, brain tissue samples from patients with LRRK2 mutations had greater levels of phosphorylated s15 than seen in controls.
Next, the researchers investigated whether phosphorylation could be linked to cell death, by studying nerve cells derived from rats or from human . Genetically engineering the cells to have a LRRK2 mutant gene increased the amount of cell death and phosphorylated s15. In contrast, the researchers prevented cell death when they engineered the cells to also make a mutant s15 protein that could not be tagged by LRRK2.
"These results suggest that s15 ribosome protein may play a critical role in the development of Parkinson's disease," said Dr. Dawson.
How might phosphorylation of s15 kill nerve cells? To investigate this, Dr. Dawson and his colleagues performed experiments on fruit flies.
Previous studies on flies showed that genetically engineering dopamine-releasing  to overproduce the LRRK2 mutant protein induced nerve cell damage and movement disorders. Dr. Dawson's team found that the brains of these flies had increased levels of phosphorylated s15 and that engineering the flies so that s15 could not be tagged by LRRK2 prevented cell damage and restored normal movement.
Interestingly, the brains of the LRRK2 mutant flies also had abnormally high levels of all proteins, suggesting that increased s15 tagging caused ribosomes to make too much protein. Treating the flies with low doses of anisomycin, a drug that blocks protein production, prevented  and restored the flies' movement even though levels of s15 phosphorylation remained high.
"Our results support the idea that changes in the way cells make proteins might be a common cause of Parkinson's disease and possibly other neurodegenerative disorders," said Dr. Dawson.
Dr. Dawson and his colleagues think that blocking the phosphorylation of s15 ribosomal proteins could lead to future therapies as might other strategies which decrease bulk protein synthesis or increase the ' ability to cope with increased protein metabolism. They also think that a means to measure s15 phosphorylation could also act as a biomarker of LRRK2 activity in treatment trials of LRRK2 inhibitors.
More information: Martin et al. "Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease," Cell, April 10, 2014. DOI: 10.1016/j.cell.2014.01.064

Getting to the root of Parkinson's disease

April 10, 2014
Johns Hopkins Medicine
Working with human neurons and fruit flies, researchers have identified and then shut down a biological process that appears to trigger a particular form of Parkinson’s disease present in a large number of patients. The new research builds on a growing body of knowledge about the origins of Parkinson's disease, whose symptoms appear when dopamine-producing nerve cells in the brain degenerate.

Working with human neurons and fruit flies, researchers at Johns Hopkins have identified and then shut down a biological process that appears to trigger a particular form of Parkinson's disease present in a large number of patients. A report on the study, in the April 10 issue of the journal Cell, could lead to new treatments for this disorder.

"Drugs such as L-dopa can, for a time, manage symptoms of Parkinson's disease, but as the disease worsens, tremors give way to immobility and, in some cases, to dementia. Even with good treatment, the disease marches on," says Ted Dawson, M.D., Ph.D., professor of neurology and director of the Johns Hopkins Institute for Cell Engineering,
Dawson says the new research builds on a growing body of knowledge about the origins of Parkinson's disease, whose symptoms appear when dopamine-producing nerve cells in the brain degenerate. Further evidence for a role of genetics in Parkinson's disease appeared a decade ago when researchers identified key mutations in an enzyme known as leucine-rich repeat kinase 2, or LRRK2 -- pronounced "lark2." When that enzyme was cloned, Dawson, together with his wife and longtime collaborator Valina Dawson, Ph.D., professor of neurology and member of the Institute for Cell Engineering, discovered that LRRK2 was a kinase, a type of enzyme that transfers phosphate groups to proteins and turns proteins on or off to change their activity.
Over the years, it was found that blocking kinase activity in mutated LRRK2 halted degeneration, while enhancing it made things worse. But nobody knew what proteins LRRK2 was acting on.
"For nearly a decade, scientists have been trying to figure out how mutations in LRRK2 cause Parkinson's disease," said Margaret Sutherland, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke. "This study represents a clear link between LRRK2 and a pathogenic mechanism linked to Parkinson's disease."
Dawson went fishing for the right proteins using LRRK2 as bait. When his team began to identify those proteins, Dawson says they were surprised to discover that many were linked to the cellular machinery, like ribosomes, that make proteins. Nobody, says Dawson, suspected that LRRK2 might be involved at such a basic level as protein manufacture.
Unsure if they were right, the team then tested the proteins they identified to see which of them, if any, LRRK2 could add phosphate groups to. They came up with three ribosomal protein candidates -- s11, s15 and s27. They then altered each ribosomal protein to see what would happen. It turned out that mutating s15 in a manner that blocked LRRK2 phosphorylation protected nerve cells taken from rats, humans and fruit flies from death. In other words, s15 appeared to be the much sought-after target of LRRK2, Dawson says.
"When you go fishing, you want to catch fish. We just happened to catch a big one," Dawson says.
With the protein now identified, Dawson's team is tackling further experiments to find out how excess protein production causes dopamine neurons to degenerate. And they want to see what happens when they block LRRK2 from phosphorylating the s15 protein in mice, to build on their findings from fruit flies and nerve cells grown in a dish.
"There's a big chasm between animal disease models and human treatments," says Ian Martin, Ph.D., a neuroscientist in Dawson's lab and the lead author on the paper. "But it's exciting. I think it definitely could turn into something real, hopefully in my lifetime."

Story Source:
The above story is based on materials provided by Johns Hopkins MedicineNote: Materials may be edited for content and length.

Journal Reference:
  1. Ian Martin, Jungwoo Wren Kim, Byoung Dae Lee, Ho Chul Kang, Jin-Chong Xu, Hao Jia, Jeannette Stankowski, Min-Sik Kim, Jun Zhong, Manoj Kumar, Shaida A. Andrabi, Yulan Xiong, Dennis W. Dickson, Zbigniew K. Wszolek, Akhilesh Pandey, Ted M. Dawson, Valina L. Dawson. Ribosomal Protein s15 Phosphorylation Mediates LRRK2 Neurodegeneration in Parkinson’s DiseaseCell, 2014; 157 (2): 472 DOI: 10.1016/j.cell.2014.01.064

Cite This Page:
Johns Hopkins Medicine. "Getting to the root of Parkinson's disease." ScienceDaily. ScienceDaily, 10 April 2014. <>.

How Parkinson's disease starts and spreads

Injection of a small amount of clumped protein triggers a cascade of events leading to a Parkinson's-like disease in mice, according to an article published online this week in theJournal of Experimental Medicine
                                                                                                                                                               Progressive accumulation of clumps of the protein alpha-synuclein in the brains of patients with Parkinson's disease coincides with the onset of . However, whether these clumps are sufficient to trigger neurodegeneration, and how these clumps spread throughout the brain, remained unclear.
To answer these questions, a team led by Virginia M.Y. Lee at the University of Pennsylvania School of Medicine studied mice expressing a mutated form of alpha-synuclein found in patients with Parkinson's disease. These mice show symptoms of disease around one year of age but not earlier.
Lee and colleagues found that injecting preformed clumps of human alpha-synuclein into the brains of young mice accelerated disease onset and severity. These clumps seemed to act as "seeds" that recruited even the mouse version of alpha-synuclein into new clumps, which then spread throughout the brain. The pattern of spreading from neuron to neuron suggests that the clumps may hijack the highway traveled by normal brain signals.
These findings suggest that Parkinson's disease, like other including Alzheimer's, may start and progress due to abnormal aggregation and accumulation of proteins within the brain. What gets these clumps going in the first place remains unclear.
More information: Hung, L.W., et al. 2012. J. Exp. Meddoi:10.1084/jem.20112285

Shape-shifting disease proteins may explain variable appearance of neurodegenerative diseases

Altered protein shapes may explain differences in some brain diseases
Accumulations of alpha-synuclein (red) and tau (green) were found in mouse brain cells that had been treated with strain B. Overlap of the two proteins is shown in yellow. Credit: Courtesy of Dr. Virginia M.Y. Lee, University of Pennsylvania School of Medicine.
Neurodegenerative diseases are not all alike. Two individuals suffering from the same disease may experience very different age of onset, symptoms, severity, and constellation of impairments, as well as different rates of disease progression. Researchers in the Perelman School of Medicine at the University of Pennsylvania have shown one disease protein can morph into different strains and promote misfolding of other disease proteins commonly found in Alzheimer's, Parkinson's and other related neurodegenerative diseases.
Virginia M.Y. Lee, PhD, MBA, professor of Pathology and Laboratory Medicine and director of the Center for Neurodegenerative Disease Research, with co-director, John Q. Trojanowski MD, PhD, postdoctoral fellow Jing L. Guo, PhD, and colleagues, discovered that alpha-synuclein, a protein that forms sticky clumps in the neurons of Parkinson's disease patients, can exist in at least two different structural shapes, or "strains," when it clumps into fibrils, despite having precisely the same.
These two strains differ in their ability to promote fibril formation of normal alpha-synuclein, as well as the , which forms neurofibrillary tangles in individuals with Alzheimer's disease.
Importantly, these alpha-synuclein strains are not static; they somehow evolve, such that fibrils that initially cannot promote tau tangles acquire that ability after multiple rounds of "seeded" fibril formation in test tubes.
The findings appear in the July 3rd issue of Cell.
Morphed Misfolding Proteins Found In Overlapping Neurodegenerative Diseases
Tau and alpha-synuclein protein  are hallmarks of separate diseases – Alzheimer's and Parkinson's, respectively. Yet these two proteins are often found entangled in diseased brains of patients who may manifest symptoms of both disorders.
One possible explanation for this convergence of Alzheimer's and Parkinson's  in the same patient is a global disruption in . But, Guo and Lee showed that one strain of alpha-synuclein  which cannot promote tau fibrillization actually evolved into another strain that could efficiently cause tau to fibrillize in cultured neurons, although both strains are identical at the amino acid sequence level. Guo and Lee called the starting conformation "Strain A," and the evolved conformation, "Strain B."

Research shows that a human protein may trigger the Parkinson's disease

A research led by the Research Institute Vall d'Hebron (VHIR), in which the University of Valencia participated, has shown that pathological forms of the α-synuclein protein present in deceased patients with Parkinson's disease are able to initiate and spread the neurodegenerative process that typifies this disease in mice and primates. The discovery, published in the March cover of Annals of Neurology, opens the door to the development of new treatments that stop the progression of Parkinson's disease, aimed at blocking the expression, the pathological conversion and the transmission of this protein.
Recent studies have shown that synthetic forms of α-synuclein are toxic for neurons, both in vitro (cell culture) and in vivo (mice), which can spread from one cell to another. However, until now it was not known if this pathogenic synthetic capacity could be extended to the pathological human protein found in patients with Parkinson's and, therefore, whether it was relevant for the disease in humans.
In the present study, led by Doctor Miquel Vila, from the group of Neurodegenerative Diseases of the VHIR and CIBERNED member, the researchers extracted α-synuclein aggregates from brains of dead Parkinson's-afflicted patients to inject them into the brains of rodents and primates.
Four months after the injection into mice, and nine months after the injection into monkeys, these animals began to present degeneration of dopaminergic neurons and intracellular cumulus of α-synuclein pathology in these cells, as occurs in Parkinson's disease. Months later, the animals also showed cumulus of this protein in other brain remote areas, with a pattern of similar extension to that observed in the brains of patients after years of disease evolution.
According to Doctor Vila, these results indicate that "the pathological aggregates of this protein obtained from patients with the Parkinson's disease have the ability to initiate and extend the neurodegenerative process that typifies Parkinson's disease in mice and primates," a discovery that, he adds, "provides new insights about the possible mechanisms of initiation and progression of the disease and opens the door to new therapeutic opportunities."
Therefore, the next step is to find out how to stop the progression and spread of the disease, by blocking the cell-to- cell transmission of of α-synuclein, as well as regulating the levels of expression and stopping the pathological conversion of this protein.
Parkinson's disease
Parkinson's disease is the second-most common neurodegenerative disease after Alzheimer's disease. It is characterized by progressive loss of neurons that produce dopamine in a brain region (the substantia nigra of the ventral midbrain) and the presence in these cells of pathological intracellular aggregates of α-synuclein protein, called Lewy bodies. The loss of brain dopamine as a consequence of neuronal death results in the typical motor manifestations of the disease, such as muscle stiffness, tremors and slow movement.
The most effective treatment for this disease is the levodopa, a palliative drug that restores the missing dopamine. However, as the disease progresses, the pathological process of neurodegeneration and accumulation of α-synuclein progressively extends beyond the ventral midbrain to other brain areas. As a result, there is a progressive worsening of the patient and the emergence of non-motor clinical manifestations unresponsive to dopaminergic drugs. There is currently no treatment that avoids, delays or halts the progressive evolution of the neurodegenerative process.
More information: Ariadna Recasens, Benjamin Dehay, Jordi Bové, Iria Carballo-Carbajal, Sandra Dovero, Ana Pérez-Villalba, Pierre-Olivier Fernagut, Javier Blesa, Annabelle Parent, Celine Perier, Isabel Fariñas, José A. Obeso, Erwan Bezard and Miquel Vila. "Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys." Annals of Neurology Volume 75, Issue 3, March 2014, Pages: 351–362. DOI: 10.1002/ana.24066

Temporary 'Tattoo' Could Help Patients With Parkinson's, Epilepsy

This is one tattoo you might not regret.
Researchers at the University of Texas-Austin have developed an ultra-thin, temporary tattoo-like device that could store patients' medical information and release medicine directly into their skin — a first for bio-integrated electronics.
This breakthrough could revolutionize patient care. For example, it could one day be used to treat patients with diseases such as Parkinson's or epilepsy by tracking their movement , according to Nature.
It uses soft, flexible materials that house a 4-centimeter long, 2-centimeter wide, .3-millimeter thick device that contains sensors, RAM capabilities, microheaters and medicine. The patch sticks to skin through electrostatic force as any adhesives would disrupt electrical connectivity.
Electronic Tattoo

"This technology could help electronics that interact with humans be more mechanically compatible," Nanshu Lu, an assistant professor at UT-Austin who co-authored the study, said in a statement. "In terms of application, its uses range from consumer products like rollable displays and solar cells, to personal digital health care like EKG and emotion sensors, to computer gaming."
But doctors are still a long way off from putting the device to practical use. It only works if it's connected to a power source and data transmitter, and researchers need to find a way to make these compact and flexible as well, Lu told Nature. Plus, the data it collects would need to be converted into a readable format for doctors to make use of it.
Many other recent advancements use electronic "skin," including a patch that can monitor body temperature. There's also a sensor that attaches to prosthetic limbs and allows the wearer to register things like touch and temperature. Google filed a patent in November for an electronic tattoo that could act as a microphone and lie detector.
The research, for which Lu was awarded a National Science Foundation Faculty Early Career Development Award, was published in Nature Nanotechnology at the end of March.