Parkinsons Disease / Covid 19 & Parkinsons

This forum is to discuss general things concerning TSOI.
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

Tips for Making Your Daily Life With Parkinson’s Disease Easier

4/1/21 ... fe-easier/

You’ve likely seen numerous tips for making your life more organized and easier to navigate. Well, the following are tips I have found that can make life easier if you live with Parkinson’s disease.

Begin by making your home safer. Pick up anything off the floor that may be a tripping hazard. Find a better place to store it. For example, instead of leaving your shoes on the floor, hang them by their shoelaces over the handle of the coat closet. This little trick also eliminates the need to bend over and pick them up off the floor.

Move your bed so that the side you sleep on is nearest the wall. Install a grab bar onto the wall alongside the bed to make it easier to get up and out.

A tip for those who find it difficult to turn over in bed: Use satin sheets and satin pajamas for sleeping. You may want to start out with either sheets or pajamas first and graduate to both if the satin doesn’t prove too slippery for you.

In the bathroom, I recommend a portable toilet seat that allows you to adjust the height. It will make it easier to get on and off the toilet.

Should you have a power outage, have a couple flashlights readily available in easy-to-access spots. Adhere glow-in-the-dark tape on the handles of your flashlights so that you can easily find them.

A number of tips can help in the hygiene area. When you are showering or bathing, give up your washcloth and try bath mitts instead. Bath mitts are a bit more coarse and leave your skin feeling smooth. To clean, they can easily be thrown in with a load of towels.

When you have Parkinson’s, drying your hair can be a frustrating task. A wall mount may be a game-changer. It holds your hair dryer, freeing your hands to style.

When shopping for clothes, choose shirts with multiple colors and patterns. If you tend to spill while eating, most spills won’t show up. Tie-dyed shirts are great at deceiving the eye!

Wearing tube socks can make getting dressed simpler. They are easier to put on than regular socks, which are shaped like a foot. Also, you can sew loops partway down the inside of each sock and use them to pull on your socks, eliminating some of the frustration.

An age-old piece of wisdom, or the best tip for those with Parkinson’s: When you are frustrated, take a deep breath and count to 10. When dealing with this disease, stress will only make things harder. Instead, I’m all about making life easier. Ax the stress, try one of the recommendations above, and share your favorite tip or trick in the comments below.
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

Magnetic Nanoparticles May Help Restore Brain Function

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Magnetic nanoparticles may help restore brain function by directing nerve cell growth, a new study shows.

Researchers believe this technology has therapeutic potential and may be used in the development of new treatments for Parkinson’s disease,

The study, “Magnetic spatiotemporal control of SOS1 coupled nanoparticles for guided neurite growth in dopaminergic single cells,” was published in the journal Nature Scientific Reports.

Parkinson’s disease is characterized by the loss of neurons, or nerve cells, that produce the neurotransmitter dopamine — a chemical messenger essential for muscle control.

Restoring brain function after nerve damage has occurred remains an issue in treating neurodegenerative diseases, such as Parkinson’s.

“Regeneration in the central nervous system [comprised of the brain and spinal cord] is only possible to a very limited degree as the regenerating neurite, the axon, comes into contact with proteins that have growth-inhibiting properties,” according to a press release from Ruhr University Bochum (RUB), in Germany.

Moreover, after nerve damage or injury, these nerve cell projections, or neurites — which conduct electrical impulses to other nerve cells — do not know in which direction to grow.

“The regenerating axon [neurite] also does not initially know in which direction it needs to grow to reach and functionally connect the denervated target tissue,” said Rolf Heumann, PhD, senior researcher for molecular neurobiochemistry at RUB and the study’s lead investigator.

In previous studies, the same research team showed that a family of proteins, known as Ras, was able to transmit signals within nerve cells, protecting them from degeneration and promoting nerve fiber growth. These proteins alternate between an active and inactive state and can be regulated by a Ras-regulating switch protein.

Now, researchers investigated the growth of nerve fibers and the use of magnetic nanoparticles to guide their growth in model nerve cells.

“The long-term goal of our study is to promote the regeneration of transplanted dopaminergic neurons using functionalised magnetic nanoparticles in the brain,” Heumann said.

Using imaging techniques, the team was able to demonstrate that magnetic tiny nanoparticles successfully bind to the Ras-regulating switch protein, within minutes, and successfully transport it to the cell membrane where the Ras protein is located.

“We initially showed that we were able to move the ferrous nanoparticles within neurons in a controlled manner using magnetic tips,” said Fabian Raudzus, PhD, a member of the faculty of chemistry and biochemistry at RUB and an author of the study.

When researchers implanted these nanoparticles — using a mechanical pressure method — into neurites they saw that the particles accumulated at their tip, where the direction of nerve cells growth is determined. Importantly, the team observed that they could load large numbers of model nerve cells with these nanoparticles without disrupting the induction of their growth.

“These results will serve as an initial step to develop tools for refining cell replacement therapies based on grafted human induced dopaminergic neurons loaded with functionalized magnetic nanoparticles in Parkinson model systems,” the researchers wrote.

“Although we are still far from a clinical application, we hope that our experiments represent a first step towards supporting the regeneration of transplanted dopaminergic neurons in the treatment of Parkinson’s,” Heumann said.
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

How Our Perception of Pain Influences the Way We Manage It

4/2/21 ... anagement/

“Dr. C seems better these days, don’t you think?” Neo asks Mrs. Dr. C. Neo is the inner part of Dr. C’s brain that shares his insights on Parkinson’s disease, science, and general well-being.

Mrs. Dr. C agrees. “Since we moved to where winter snow doesn’t linger into April, he’s out gardening more. We do our walks in the yard and love discovering new blooms. He is excited about writing a new book. His sleep ritual has improved, and meditating twice a day, morning and night, has decreased pain levels. It also helps that our stress levels are a lot lower.”

“I’ve noticed that his eating habits have changed. Do you think that’s made a difference?” Neo frowns at his extra winter weight.

“I’m sure it has,” says Mrs. Dr. C. She knows the biggest change has been eliminating foods with a high refined sugar content, such as candy, cookies, and ice cream. “To ease the cravings, he eats small amounts of 80% cacao dark chocolate. He said that this dietary change has improved his sleep, meditation, and pain management.”

“I’d like to know more,” Neo says with eager enthusiasm.

“He describes pain management to me as incremental,” Mrs. Dr. C. replies. “The practice involves a series of small things done every day. Not eating high-sugar foods drops the pain perception by 10%.

“Gardening, along with muscle relaxation, drops it by 10%. Meditating twice a day manages 10%. Writing columns and working on the new book reduces another 10%. Stress management, especially physical rest, and threshold management drops the pain by 10%. And he says having me around helps another 10% — even after almost 50 years!”

Neo calculates the numbers. “If I’m doing the math, then even after all that, he still has nearly half of his pain to deal with.”

“That’s true,” Mrs. Dr. C acknowledges. “He tells me half of that remaining pain is perceptual and the other half we learn to live with.”

“You mean to tell me he’s just making it all up in his head?” Neo isn’t sold on the idea that pain is somehow make-believe.

Mrs. Dr. C clarifies. “Not exactly, Neo. We all perceive pain as real. The problem is that due to his disease and the difficulties of conductor training, the pain signals are exaggerated. It’s a hard thing to convince your brain that it is not telling you the whole truth. If you can, turn this idea of exaggerated pain into reducing your perception of the pain severity. This shift in perception along with meditative practice makes a big difference in pain management.

“One of the problems with pain is that it demands so much attention from us. Dr. C says he lives with a dozen pain focal points in his body. He calls this familiar pain, and it responds well to pain management strategies. Familiar pain does not need as much attention as it seeks. It is like a 2-year-old throwing a temper tantrum. The more attention it gets, the more the problem escalates. New pain is different. New pain requires attention because it signals that something new is malfunctioning. New pain needs to be rigorously evaluated before it can become familiar pain.”

“So how I perceive pain and how much attention I give it will affect its perceived intensity.” Neo senses that it can be a vicious cycle. “The more I pay attention to the pain, the worse it gets. As the pain gets louder, the more it demands I pay attention. Sounds terrible! This must be why people use so much pain medication.”

“I think people don’t know how to sit with their own pain long enough to understand the difference between familiar pain and new pain,” says Mrs. Dr. C. “We want to escape or fight against it. We reach out for nurturing. But we don’t take the time to really understand our pain and suffering.”

Pain is part of the human condition. According to a study in the Journal of Clinical Neuroscience, many people with Parkinson’s disease report pain as a major contributor to decreased quality of life. Our culture often falls short in treating our pain. Add to this the devastating outcomes often portrayed to people with Parkinson’s disease, and we easily end up down a dead-end alley encountering our own self-fulfilled prophecy.

Dr. C has written about the complications and mental health dangers associated with damage to the second dopamine center, the insular cortex. Learning how to adjust to this brain damage, using a shift in perception, and building new pathways limits the exaggerated effects on pain perception. It is an important part of helping people live better with this disease.

Sometimes the best pharmacy we can go to is the one between our ears.
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

Different neural circuitries linked to distinct Parkinsonian behavioral deficits

4/5/21 ... icits.aspx

Parkinson's disease (PD) is well known as a debilitating disease that gradually worsens over time. Although the disease's progression has been largely tied to the loss of motor functions, non-motor symptoms, including the loss of cognitive abilities, often emerge early in the disease.

Much less understood is the role that specific neural circuits play in these distinct motor and non-motor functions.

A new study led by neurobiologists at the University of California San Diego and their colleagues found that specific, identifiable neural pathways are charged with particular functions during stages of the disease. Their findings, published recently in Nature Neuroscience, can help form the basis for improving therapeutic strategies for precise symptoms of Parkinson's at various levels of disease progression.

The researchers used a mix of approaches to shed more light on the anatomical and functional importance of a center of brain circuitry known as the basal ganglia, located deep in the cranium. Specifically, the researchers, working in mice, investigated circuit pathways tied to specific neurons in the external globus pallidus, or GPe, and their role in different Parkinson's disease-related behaviors. The GPe is known for its strong output and influence on several downstream brain regions.

The investigations included a multi-pronged approach using electrophysiology, viral tracing and behavioral experiments. The researchers identified two populations of GPe neurons and their distinctive pathways tied to different behavioral symptoms.

" Our work demonstrates that the distinct neural circuitries in the basal ganglia are differentially involved in the motor and non-motor symptoms of Parkinsonian-like behaviors that occur at different stages of the disease. This suggests that evaluation of the detailed circuit mechanisms is needed to fully understand the changes in brain during the progression of PD, and could provide better therapeutic strategies for the treatment of PD."

- Lim, Associate Professor, Neurobiology Section of the Division of Biological Sciences, UC San Diego

Lim said the most surprising finding from the research was the fact that dopaminergic neurons, those that are gradually lost during Parkinson's disease progression, could be linked so specifically to changes in different brain areas.

"Selective manipulation of specific changes can rescue one type of symptom--without affecting other symptoms--of Parkinson's Disease," said Lim.

With the new framework in hand, Lim and his colleagues are now looking deeper at the circuit pathways and how they are tied to different disease symptom stages, in particular with an emphasis on delaying the progression of the disease.

"Our findings provide a novel framework for understanding the circuit basis of varying behavioral symptoms of the Parkinsonian state, which could provide better strategies for the treatment of PD," the researchers write in the paper.


University of California - San Diego

Journal reference:

Lilascharoen, V., et al. (2021) Divergent pallidal pathways underlying distinct Parkinsonian behavioral deficits. Nature Neuroscience.
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

New mini-microscope enables imaging of complex brain functions in freely moving mice

4/5/21 ... -mice.aspx

Researchers from the University of Minnesota Twin Cities College of Science and Engineering and Medical School have developed a unique head-mounted mini-microscope device that allows them to image complex brain functions of freely moving mice in real time over a period of more than 300 days.

The device, known as the mini-MScope, offers an important new tool for studying how neural activity from multiple regions of the outer part of the brain, called the cortex, contribute to behavior, cognition, and perception. The groundbreaking study provides new insight into fundamental research that could improve human brain conditions such as concussions, autism, Alzheimer's, and Parkinson's disease, as well as better understanding the brain's role in addiction.

The research was published today in the peer-reviewed journal Nature Methods. The study authors will also present their research at the virtual 2021 OSA Biophotonics Congress: Optics in the Life on Thursday, April 15.

In the past, scientists have studied how neural activity in specific regions of the brain's cortex contribute to behavior, but it has been difficult to study activity from multiple cortical regions at once. For mice, even the simple task of moving a single whisker in response to a stimulus involves processing information in several cortical areas. Mice are often used to study the brain because they have many of the same brain structures and connectivity as humans.

" This device enables us to image most of the mouse's brain during free and unrestrained behaviors, whereas previous mesoscale imaging was usually done in immobile mice using devices like the MRI or two photon microscopes. This new device allows us to understand how different areas of the brain interact during complex behaviors where multiple areas of the brain are working together simultaneously. This opens up research into understanding how connectivity changes in diseased states, traumatic brain injury, or addiction."

- Suhasa Kodandaramaiah, Study's Senior Author and University of Minnesota Benjamin Mayhugh Assistant Professor of Mechanical Engineering in the College of Science and Engineering

The new mini-MScope is a fluorescence microscope that can image an area about 10 millimeters by 12 millimeters and weighs about 3 grams. This allows holistic imaging of much of the mouse brain surface. The device is used for calcium imaging, a technique commonly used to monitor the electrical activity of the brain. The device mounted on the mouse's head captures images at near cellular level, making it possible to study connections between regions across the cortex.

The researchers created the miniaturized microscope using LEDs for illumination, miniature lenses for focusing, and a complementary metal-oxide-semiconductor (CMOS) for capturing images. It includes interlocking magnets that let it be easily affixed to structurally realistic 3D-printed transparent polymer skulls, known as See-Shells, that the researchers developed in previous studies. When implanted into mice, the See-Shells create a window through which long-term microscopy can be performed. The new microscope can capture the brain activity of mice for almost a year.

The researchers demonstrated the mini-MScope by using it to image mouse brain activity in response to a visual stimulus to the eye, a vibrational stimulus to the hindlimb and a somatosensory stimulus presented to the whisker. They also created functional connectivity maps of the brain as a mouse wearing the head-mounted microscope interacted with another mouse. They saw that intracortical connectivity increased when the mouse engaged in social behaviors with the other mouse.

"Our team is creating a suite of tools that will enable us to access and interface with large parts of the cortex at high spatial and temporal resolution," said Mathew Rynes, a University of Minnesota biomedical engineering Ph.D. candidate who co-led the study. "This study shows that the mini-MScope can be used to study functional connectivity in freely behaving mice, making it an important contribution to this toolkit," Rynes added.

The team had to overcome several engineering challenges to create the device.

"To image the brain in freely behaving mice, the device had to be light-weight enough to be supported and carried by the mice," said Daniel Surinach, a recent University of Minnesota mechanical engineering master's degree graduate who also co-led the study. "Within this small range, we also needed to optimize optics, electrical and imaging hardware resolution, focusing, illumination designs to provide light to the brain for imaging, and other elements to get clear images of the mouse brain during natural and vigorous behaviors. We ended up designing and testing more than 175 unique prototypes to get the finalized device working!"

The researchers are now using the mini-MScope to investigate how cortical connectivity changes in a variety of behavioral paradigms, such as exploring a new space. They are also working with collaborators who are using the mini-MScope to study how cortical activity is altered when mice learn difficult motor tasks.

"This device allows us to study the brain in ways we could have never done before," said Kodandaramaiah, who also holds appointments in the University of Minnesota's Department of Biomedical Engineering and the Medical School. "For example, we can image the mouse's brain activity as it ebbs and flows during natural movement within its space, as it goes to sleep, and when it wakes up. This provides a lot of valuable information that will help us better understand the brain to help people with disease or injury to improve their lives."

The researchers said the next steps are to improve the resolution of the imaging and study the brain at even finer detail down to examining individual neurons.


University of Minnesota

Journal reference:

Rynes, M.L., et al. (2021) Miniaturized head-mounted microscope for whole-cortex mesoscale imaging in freely behaving mice. Nature Methods.
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

Researchers generate a precise map of basal ganglia connectivity

4/5/21 ... ivity.aspx

Thousands of our daily activities, from making coffee to taking a walk to saying hello to a neighbor, are made possible through an ancient collection of brain structures tucked away near the center of the cranium.

The cluster of neurons known as the basal ganglia is a central hub for regulating a vast array of routine motor and behavior functions. But when signaling in the basal ganglia is weakened or broken, debilitating movement and psychiatric disorders can emerge, including Parkinson's disease, Tourette's syndrome, attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder.

Despite its central importance in controlling behavior, the specific, detailed paths across which information flows from the basal ganglia to other brain regions have remained poorly charted. Now, researchers at the University of California San Diego, Columbia University's Zuckerman Institute and their colleagues have generated a precise map of brain connectivity from the largest output nucleus of the basal ganglia, an area known as the substantia nigra pars reticulata, or SNr. The findings offer a blueprint of the area's architecture that revealed new details and a surprising level of influence connected to the basal ganglia.

The results, spearheaded by Assistant Project Scientist Lauren McElvain and carried out in the Neurophysics Laboratory of Professor David Kleinfeld at UC San Diego, and the laboratory of Zuckerman Institute Principal Investigator Rui Costa, are published April 5 in the journal Neuron.

The research establishes a new understanding of the position of the basal ganglia in the hierarchy of the motor system. According to the researchers, the newly identified pathways emerging from the connectivity map could potentially open additional avenues for intervention of Parkinson's disease and other disorders tied to the basal ganglia.

" With the detailed circuit map in hand, we can now plan studies to identify the specific information conveyed by each pathway, how this information impacts downstream neurons to control movement and how dysfunction in each output pathway leads to the diverse symptoms of basal ganglia diseases."

- Lauren McElvain, Assistant Project Scientist

With support from the NIH's Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, the researchers developed the new blueprint working in mice by applying a modern neuroscience toolset that combines techniques from genetics, virus tracing, automated microscopic imaging of whole-brain anatomy and image processing. The results revealed surprising new insights about the breadth of connections.

"These results are an example of how researchers supported by the BRAIN Initiative are using the latest brain mapping tools to change in a fundamental way our understanding of how the connections in the brain's circuits are organized," said John J. Ngai, director of the NIH's BRAIN Initiative.

Previous work had emphasized that the basal ganglia architecture is dominated by a closed-loop with output projections connecting back to input structures. The new study reveals the SNr broadcasts even to lower levels of the motor and behavior system. This includes a large set of brainstem regions with direct connections to the spinal cord and motor nuclei that control muscles via a small number of intervening connections.

"The new findings led by Dr. McElvain offer an important lesson in motor control," said Kleinfeld, a professor in the Division of Biological Sciences (Section of Neurobiology) and Division of Physical Sciences (Department of Physics). "The brain does not control movement though a hierarchy of commands, like the 'neural networks' of self-driving cars, but through a scheme of middle management that directs motor output while informing the executive planners."

Remarkably, according to the researchers, the SNr neurons that project to the low levels of the motor system have branched axons that simultaneously project back up to the brain regions responsible for higher-order control and learning. In this way, the newly described connectivity of SNr neurons fundamentally links operations across high and low levels of the brain.

"The fact that specific basal ganglia output neurons project to specific downstream brain nuclei but also broadcast this information to higher motor centers has implications for how the brain chooses which movements to do in a particular context, and also for how it learns about which actions to do in the future," said Costa, a professor of neuroscience and neurology at Columbia's Vagelos College of Physicians and Surgeons, as well as director and chief executive officer of the Zuckerman Institute.


University of California - San Diego

Journal reference:

McElvain, L.E., et al. (2021) Specific populations of basal ganglia output neurons target distinct brain stem areas while collateralizing throughout the diencephalon. Neuron.
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

Study indicates an amyloid link between melanoma and Parkinson’s disease

4/7/21 ... sease.aspx

On the surface, Parkinson's disease -; a neurodegenerative disorder -; and melanoma -; a type of skin cancer -; do not appear to have much in common. However, for nearly 50 years, doctors have recognized that Parkinson's disease patients are more likely to develop melanoma than the general population. Now, scientists report a molecular link between the two diseases in the form of protein aggregates known as amyloids.

The researchers will present their results today at the spring meeting of the American Chemical Society (ACS). ACS Spring 2021 is being held online April 5-30. Live sessions will be hosted April 5-16, and on-demand and networking content will continue through April 30. The meeting features nearly 9,000 presentations on a wide range of science topics.

"Several studies have shown that melanoma occurs two to six times more frequently in the Parkinson's population than the healthy population," says Dexter Dean, Ph.D., a postdoctoral fellow at the National Heart, Lung, and Blood Institute (NHLBI), who is presenting the work at the meeting. "What's more, the protein involved in Parkinson's disease, α-synuclein, is elevated in melanoma cells."

In Parkinson's disease, α-synuclein forms amyloid deposits that are thought to kill dopamine-producing neurons in the brain, causing symptoms such as tremor, slow movements and dementia. While intense research has focused on the effects of α-synuclein in the brain, much less is known about its presence or activities in other tissues. However, scientists have evidence that the amyloid-forming protein is expressed more in melanoma cells than in healthy skin.

Furthermore, higher levels of α-synuclein in melanocytes (the skin cells that give rise to melanoma) correlate with reduced pigment, or melanin, production. Melanin protects skin from damage by the sun's ultraviolet rays.

Jennifer Lee, Ph.D., Dean's postdoctoral advisor at NHLBI, part of the National Institutes of Health, had previously studied another amyloid-forming protein called premelanosomal protein (Pmel). "Most people know that amyloids are involved in diseases, such as Parkinson's and Alzheimer's, but it's less well-known that some amyloids, like Pmel, actually serve a useful function," Lee says.

In healthy melanocytes, Pmel forms amyloid fibrils that act as scaffolds to store melanin in melanosomes (the organelle where the pigment is produced, stored and transported). "Because both α-synuclein and Pmel are expressed in melanoma cells, we wondered if these two amyloid proteins could interact, and whether this interaction could be relevant to the correlation between Parkinson's disease and melanoma," Lee says.

To investigate whether α-synuclein and Pmel could interact, the researchers used microscopy and western blotting to show that the two proteins both resided in the melanosomes of human melanoma cells. When Dean added preformed α-synuclein amyloid to a test tube containing the amyloid-forming region of Pmel (known as the repeat, or RPT, domain), the α-synuclein fibrils stimulated Pmel to aggregate and form a twisted fibril structure that the protein does not normally adopt on its own.

Because α-synuclein in melanoma cells may also be found in its soluble, or non-amyloid, form, the researchers performed other in vitro experiments in which they added soluble α-synuclein to the Pmel RPT domain. In this case, α-synuclein inhibited Pmel's ability to self-aggregate and form amyloid in a concentration-dependent manner. They traced this activity to the first 60 amino acids of α-synuclein.

" We now have preliminary data that suggest an amyloid from one protein can 'seed' or template amyloid from another, and in the soluble form, α-synuclein prevents Pmel aggregation, Therefore, we think that both forms of α-synuclein could diminish melanin biosynthesis -; the amyloid form by causing Pmel to form an unusual twisted structure, and the soluble form by stopping Pmel from aggregating like it should."

- Jennifer Lee, Ph.D., Dean's Postdoctoral Advisor, NHLBI

Loss of skin pigmentation could contribute to the increased melanoma risk in Parkinson's disease patients, the researchers say.

"I think we're just at the tip of the iceberg of appreciating what α-synuclein might be doing in melanoma," Dean says. "In future experiments, I'm really interested in understanding more about what α-synuclein is doing to promote melanoma proliferation, in addition to this interaction with Pmel."


American Chemical Society
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

Step length synergy while crossing obstacles found to be lower in Parkinson’s patients

4/7/21 ... ients.aspx

A multidisciplinary research group affiliated with the Department of Physical Education's Human Movement Laboratory (Movi-Lab) at São Paulo State University (UNESP) in Bauru, Brazil, measured step length synergy while crossing obstacles in patients with Parkinson's disease and concluded that it was 53% lower than in healthy subjects of the same age and weight. Step length is one of the main variables affected by the disease.

Synergy, defined as combined operation, refers in this case to the capacity of the locomotor (or musculoskeletal) system to adapt movement while crossing an obstacle, combining factors such as speed and foot position, for example. Improving synergy in Parkinson's patients while they are walking can make a significant difference to their quality of life, as they tend to fall three times more often on average than healthy people of the same age.

" There are patients in our exercise group who fall three or four times a week. It's important to understand how these patients' gait and locomotion adapt while crossing obstacles so that we can improve step-length synergy. This approach enables us to refine the exercise protocol, improve locomotion, and try to reduce fall frequency."

- Fabio Augusto Barbieri, Professor, UNESP's Department of Physical Education and its Movement Science Graduate Program

An article on the study is published in the journal Gait & Posture. Barbieri is the last author. The first author is mechanical engineer Satyajit Ambike, a professor in the Department of Health and Kinesiology at Purdue University in the United States. The study is the first to report on impaired locomotor synergies in Parkinson's patients.

"The innovation in our study is its focus on gait timing, or rhythmicity, the constancy with which patients position their feet to maintain locomotion," Barbieri said. "This can be evaluated by measuring step-length synergy. Synergy presupposes a goal and has to do with the way the locomotor system adjusts to achieve it. In our case, we investigated how the system adapts to achieve the objective of crossing an obstacle during locomotion."

The researchers found that Parkinson's patients are less able to adapt the position of their feet than healthy people as they approach and cross an obstacle. "The locomotor system always tries to adapt in order to maintain constancy during locomotion. Absent this constancy, we may make mistakes that can lead to a fall," Barbieri said. "Parkinson's patients are less constant in positioning their feet while walking, and gait timing tends to be unstable as a result. Their speed rises and falls as they walk, and step length varies along with foot placement."


Thirteen Parkinson's patients and 11 neurologically healthy controls participated in the study. All participants were over 50. To be eligible they had to be able to walk without assistance, to have normal sight and hearing (with or without lenses and hearing aids), to have no orthopedic or neurological diseases apart from Parkinson's, and to be able to understand and follow instructions. The patients took medication for Parkinson's (Levodopa) for at least three months before data collection.

The participants had to walk along a gangway (length 8.5 m, width 3.5 m), and cross a foam rubber obstacle (height 15 cm, width 60 cm, depth 5 cm) placed 4 m from the starting point. Gait speed was not imposed but chosen by each participant. No instructions were given regarding which leg should cross the obstacle first, but its position was adjusted for each participant so that the right leg had to lead.

"We tried to standardize the task so that all the subjects crossed the obstacle with their right leg leading," Barbieri said. "The idea was to ensure there was no interference from other factors in the locomotion pattern. The height of the obstacle was 15 cm because that's the standard curb height in Brazil. We thought it would be best to stick to the standard."

A number of systems need to work together for synergy to happen in terms of achieving an objective, he explained. "When the distance between the toes and the obstacle [before it is crossed] and between the heel and the obstacle [after it is crossed] varies a lot, the risk of contacting the obstacle increases. Being too close to the obstacle before crossing entails having to raise the leading leg so high that it may prove impossible. If the trailing foot comes down too close to the obstacle after crossing, the heel is likely to touch it," he said, adding that gait timing should ideally be constant and the foot should not come too close to the obstacle on either side.


Step-length synergy was measured using a methodology derived from mechanical engineering and adapted to the study of human movement. The methodology is not specific to gait analysis or Parkinson's, but adapted from a set of techniques used to measure upper-limb strength by Ambike and Mark Latash of Pennsylvania State University.

Eight motion capture cameras used in the study were purchased with funding from FAPESP (grant no. 2017/19516-8). The study was also supported by a visiting researcher grant.

Twenty reflective markers were placed according to a specific gait analysis model on the body of each participant in the experiment. "While the subject is walking along the gangway toward the obstacle and crossing it, the cameras emit infrared light, which is reflected by the markers. The cameras capture the position of the markers, enabling us to determine step length and duration. Gait analysis software does the other calculations," Barbieri explained.

The study was the first time this methodology was applied to gait analysis, according to Barbieri. "Another innovation was that we used a single variable to detect possible gait timing-related incapacities relatively simply, facilitating more consistent future intervention to improve gait timing via training," he said. "This is the point of gait analysis in general. You want to determine possible variables of changes in gait and modify intervention on that basis."

The same researchers have since begun a study to find out whether the height of the obstacle affects step-length synergy. "We want to know if this synergy changes because the obstacle is higher or lower. This concerns the environment in which the patient moves. If there are obstacles of a certain height in the area, they may cause problems and lead to falls, so we can modify the environment to facilitate locomotion," Barbieri said.


Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Journal reference:

Ambike, S., et al. (2021) Step length synergy while crossing obstacles is weaker in patients with Parkinson’s disease. Gait & Posture.
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

Research on mysterious gene may lead to new treatments for Parkinson’s disease

4/8/21 ... sease.aspx

More than 20 years after the discovery of the parkin gene linked to young-onset Parkinson's disease, researchers at The Ottawa Hospital and the University of Ottawa may have finally figured out how this mysterious gene protects the brain.

Using human and mouse brain samples and engineered cells, they found that the parkin protein works in two ways. First, it acts like a powerful antioxidant that disarms potentially harmful oxidants in the brain, including dopamine radicals.

Second, as the brain ages and dopamine radicals continue to build up, parkin sequesters these harmful molecules in a special storage site within vulnerable nerve cells, so they can continue to function normally throughout our lifespan.

In people with mutations in both copies of the parkin gene, these protective effects are missing, and as a result Parkinson's develops before the age of 40 years. If confirmed, the results could point the way towards the development of new treatments.

" If we could deliver antioxidants or a healthy copy of the parkin gene into the brains of people with these mutations, this could help slow down or even halt early-onset Parkinson's."

- Dr. Julianna Tomlinson, Co-Corresponding Author and Scientific Project Manager

"What we don't know yet is whether such an approach could also benefit individuals with late-onset Parkinson's that is not linked to the parkin gene," added co-corresponding author Dr. Michael Schlossmacher, neurologist and Director of Neuroscience at The Ottawa Hospital. "We are eager to investigate this."


University of Ottawa

Journal reference:

Tokarew, J. M., et al. (2021) Age-associated insolubility of parkin in human midbrain is linked to redox balance and sequestration of reactive dopamine metabolites. Acta Neuropathologica.
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Re: Parkinsons Disease / Covid 19 & Parkinsons

Post by trader32176 »

Parkinson's disease, type 2 diabetes, and cancer share the same pathway, shows study

4/8/21 ... study.aspx

When cells are stressed, chemical alarms go off, setting in motion a flurry of activity that protects the cell's most important players. During the rush, a protein called Parkin hurries to protect the mitochondria, the power stations that generate energy for the cell.

Now Salk researchers have discovered a direct link between a master sensor of cell stress and Parkin itself. The same pathway is also tied to type 2 diabetes and cancer, which could open a new avenue for treating all three diseases.

"Our findings represent the earliest step in Parkin's alarm response that anyone's ever found by a long shot. All the other known biochemical events happen at one hour; we've now found something that happens within five minutes," says Professor Reuben Shaw, director of the NCI-designated Salk Cancer Center and senior author of the new work, detailed in Science Advances on April 7, 2021. "Decoding this major step in the way cells dispose of defective mitochondria has implications for a number of diseases."

Parkin's job is to clear away mitochondria that have been damaged by cellular stress so that new ones can take their place, a process called mitophagy. However, Parkin is mutated in familial Parkinson's disease, making the protein unable to clear away damaged mitochondria.

While scientists have known for some time that Parkin somehow senses mitochondrial stress and initiates the process of mitophagy, no one understood exactly how Parkin was first sensing problems with the mitochondria--Parkin somehow knew to migrate to the mitochondria after mitochondrial damage, but there was no known signal to Parkin until after it arrived there.

Shaw's lab, which is well known for their work in the fields of metabolism and cancer, spent years intensely researching how the cell regulates a more general process of cellular cleaning and recycling called autophagy.

About ten years ago, they discovered that an enzyme called AMPK, which is highly sensitive to cellular stress of many kinds, including mitochondrial damage, controls autophagy by activating an enzyme called ULK1.

Following that discovery, Shaw and graduate student Portia Lombardo began searching for autophagy-related proteins directly activated by ULK1. They screened about 50 different proteins, expecting about 10 percent to fit.

They were shocked when Parkin topped the list. Biochemical pathways are usually very convoluted, involving up to 50 participants, each activating the next. Finding that a process as important as mitophagy is initiated by only three participants--first AMPK, then ULK1, then Parkin--was so surprising that Shaw could scarcely believe it.

To confirm the findings were correct, the team used mass spectrometry to reveal precisely where ULK1 was attaching a phosphate group to Parkin. They found that it landed in a new region other researchers had recently found to be critical for Parkin activation but hadn't known why. A postdoctoral fellow in Shaw's lab, Chien-Min Hung, then did precise biochemical studies to prove each aspect of the timeline and delineated which proteins were doing what, and where.

Shaw's research now begins to explain this key first step in Parkin activation, which Shaw hypothesizes may serve as a "heads-up" signal from AMPK down the chain of command through ULK1 to Parkin to go check out the mitochondria after a first wave of incoming damage, and, if necessary, trigger destruction of those mitochondria that are too gravely damaged to regain function.

The findings have wide-ranging implications. AMPK, the central sensor of the cell's metabolism, is itself activated by a tumor suppressor protein called LKB1 that is involved in a number of cancers, as established by Shaw in prior work, and it is activated by a type 2 diabetes drug called metformin.

Meanwhile, numerous studies show that diabetes patients taking metformin exhibit lower risks of both cancer and aging comorbidities. Indeed, metformin is currently being pursued as one of the first ever "anti-aging" therapeutics in clinical trials.

"The big takeaway for me is that metabolism and changes in the health of your mitochondria are critical in cancer, they're critical in diabetes, and they're critical in neurodegenerative diseases," says Shaw, who holds the William R. Brody Chair.

" Our finding says that a diabetes drug that activates AMPK, which we previously showed can suppress cancer, may also help restore function in patients with neurodegenerative disease. That's because the general mechanisms that underpin the health of the cells in our bodies are way more integrated than anyone could have ever imagined."

- Reuben Shaw, Professor and Director, NCI-designated Salk Cancer Center


Salk Institute

Journal reference:

Hung, C-M., et al. (2021) AMPK/ULK1-mediated phosphorylation of Parkin ACT domain mediates an early step in mitophagy. Science Advances.
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