Heatwave - keeping cool when you have Parkinson's

Heat-related deaths and illnesses are preventable. Despite this fact, over 600 people die each year from heat-related illnesses, according to the #CDC. Share this with your patients and friends as a friendly reminder to stay cool and hydrated. 

If you're concerned about your symptoms getting worse in

the heat, we've prepared some information to help.

Tips for coping with the heat

Keep hydrated

Make sure you drink plenty of water and fruit juice and avoid tea, coffee and alcohol.

Stay indoors

Try to avoid any strenuous activity. If you can, stay indoors between 11am and 3pm when the sun is at its hottest. If you do go out, make sure you stay in the shade where possible.

Stock up on supplies

People with Parkinson's may find their symptoms worsen in the heat. Try to make sure you have enough medication and plenty of food and drink at home, so you don't need to go out when the sun is at its hottest.

Keep your cool

Try to stay cool by wearing loose cotton clothing and by splashing cold water on your face or the back of your neck. Try and identify which is the coolest room in the house, so you can stay there during the heat of the day.

For anyone who uses the Neupro (rotigotine) patch

Make sure that the patch is kept out of direct sunlight. If you're wearing it outside it's recommended to cover the patch with loose clothing and to avoid prolonged exposure to the heat. You must store Neupro below 25 degrees Celsius or (25°C × 9/5) + 32 = 77°Fahrenheit).

If you feel unwell

If you start to feel unwell, make sure you drink water or fruit juice, and try to find somewhere cool to rest. If possible, have a wash to cool down.

If you experience symptoms such as breathlessness, chest pain, confusion, dizziness, weakness or any cramps start to get worse or don't go away, you may be suffering from heat exhaustion.

There's no need to panic but you will need to seek medical help immediately.

https://youtu.be/_zBZrPfqQYA

Oldie but Goodie: What Parkinson’s Isn’t: 6 Myths Debunked

 By Allison Smith · August 21, 2017

What is Parkinson’s disease? This is a question many of us have asked our neurologists, but the answers can be confusing. This is because we are still learning about this disorder and it’s impact on our lives. However, we do know what Parkinson’s isn’t.

Myth: Parkinson’s is curable

First and foremost, as many of you know, there is no cure for Parkinson’s disease. But before you get too discouraged, if you’re going to get it, now is a great time to be diagnosed with Parkinson’s. We have made such huge medical advances in the last decade alone, that now we have an arsenal of weapons to use against PD. Imagine being diagnosed with Parkinson’s in the early 1900’s… I shudder.

Myth: Parkinson’s only affects movement

Since its discovery in 1817, Parkinson’s disease was believed to only affect posture, mobility, gait, and balance. But now we realize just how PD can impact a person in a multitude of ways, including non-motor symptoms. Top offenders include: constipation, bladder control, drooling, swallowing, memory, depression, anxiety, sleep issues, cognition, and impaired executive functioning. Our Neurologists have their work cut out for them.

Myth: Parkinson’s will kill you

Although you won’t die from having Parkinson’s disease, you can die from its complications. This can include aspiration of food, traumatic falls, infection, or sepsis. Just remember, you don’t die from Parkinson’s disease, you die with it.

Myth: Parkinson’s is an old person’s disease

Although PD is more common in the elderly population, there is a subset of Parkies who are under the age of 40. Like yours truly…

Myth: Parkinson’s is gender-specific

Even though there are more men diagnosed with Parkinson’s disease than women, PD doesn’t discriminate. Some of the major differences between the sexes of Parkies is hormone levels, coping skills, lifestyle choices and careers (men could possibly be more exposed to chemicals, such as pesticides).

Myth: Parkinson’s is a walk in the park

When I was first diagnosed with Parkinson’s disease, I was naïve to believe that I would only be inconvenienced by a slower pace or struggle with a slight tremor. That was based on the only person I knew who had Parkinson’s… Michael J. Fox. He didn’t look that bad. Maybe I will get a mild case of PD… kind of like the watered-down version. Ignorance is bliss, eh?

Oh man, was I wrong. I learned quickly that Parkinson’s would negatively impact many facets of my life and that each day will present a challenge of some sort. Parkinson’s isn’t a walk in the park. It is emotionally, physically, and mentally exhausting. But the one thing that you can count on is your Wolfpack (people who support you). They will take that stroll with you through the botanical garden of life.

https://parkinsonsdisease.net/living/what-parkinsons-isnt-myths-debunked/

How a gut infection might spark Parkinson's

July 19, 2019     By Tim Newman

Over recent years, researchers have become increasingly interested in the link between the immune system and Parkinson's disease. Using a mouse model, scientists recently explored the potential role of a bacterial gut infection.

Parkinson's disease develops due to the slow depletion of dopamine-producing neurons in a part of the brain called the substantia nigra.

This region of the brain plays an important role in movement, so symptoms include shaking, tremor, and rigidity.

The primary risk factor for Parkinson's is age and, as the population of the United States is slowly aging, the number of cases is steadily growing.

Some believe that we are approaching a Parkinson's pandemic; globally, between 1990–2015, the number of Parkinson's cases has doubled to more than 6 million.

Some predict the number to double again to 12 million by 2040.

Although researchers have studied the disease for decades, they still have many questions about how and why brain cells are destroyed.

Parkinson's and the immune system

More recently, links between the immune system and Parkinson's have come to the fore. Evidence is slowly mounting that Parkinson's might have an autoimmune component.

Autoimmune diseases are conditions where an individual's immune system confuses the body's cells for pathogens and destroys them.

A recent study, published in Nature, tests this theory further; the researchers hail from the Université de Montréal, the Montreal Neurological Institute, and McGill University, all in Canada.

Around 10 percent of Parkinson's cases are due to mutations in genes that code for the proteins PINK1 and Parkin, which play a role in clearing out damaged mitochondria.

Individuals who carry these mutations are more likely to develop Parkinson's at an earlier age — before the age of 50.

However, when scientists knock these genes out of mice, the mice do not develop Parkinson's disease or any similar symptoms. Why these knock-out mice are immune to Parkinson's has foxed researchers.

According to the authors, it means that "factors other than the loss of function of these proteins are likely to be required to trigger Parkinson's." They set out to identify these other factors.

Joining the dots

The authors wanted to find further evidence that there is a link between PINK1 and Parkin proteins, mitochondria, the immune system, and Parkinson's.

They believe that knock-out mice do not develop Parkinson's because of how the researchers have reared them. The mice used in these studies are typically germ-free, meaning that they have never encountered bacteria.

So, to test this hypothesis, they infected young mice that lacked PINK1 and Parkin with Escherichia coli. This caused mild intestinal symptoms in the mice.

As expected, the early-life infection triggered the occurrence of Parkinson's-like motor symptoms as they got older. The scientists also identified a loss of dopaminergic neurons in their brains.

When the scientists gave the mice L-DOPA — a drug used to treat the symptoms of Parkinson's — their symptoms improved, inferring that the condition has similarities to the human condition.

In mice with normal versions of PINK1 and Parkin, the immune system deals with pathogens appropriately. However, the authors believe that in animals without the Parkinson's-related genes, the gut infection triggers an abnormal immune response that overruns and attacks healthy cells.

A complex tale

The new findings build on earlier work by the same group of researchers that showed a relationship between genes, mitochondria, and the immune system.

In the previous study, they showed that PINK1 and Parkin suppress a mitochondria-based pathway that promotes an immune response to inflammation. They infer that in individuals without functioning copies of PINK1 and Parkin, the immune response might be allowed to spill over and continue unabated.

In their latest study, the scientists identified T lymphocytes that responded to host tissues in the brains of the mice. When they tested these cells in a culture dish, the cells attacked healthy neurons. The authors state that:

"

These data [...] provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson's disease, which highlights the relevance of the gut–brain axis in the disease."

In the classic model of Parkinson's disease, dopaminergic neurons die because toxic proteins build up inside the cells. This study, however, suggests that an overzealous immune response that might have been sparked years earlier destroys the cells.

This study does not conclude that all cases of Parkinson's disease are autoimmune, but the results do imply that there is a role for the immune system.

Of course, this work was carried out in a mouse model, so there is no guarantee that the findings will relate to humans. Also, not all people with Parkinson's disease have mutations in the genes that code for PINK1 and Parkin, so it is not clear whether similar mechanisms are involved in all cases.

It will be some time before Parkinson's gives up all of its secrets, but it seems that the story will involve an interplay between the immune system, genetics, mitochondria, and the brain.

https://www.medicalnewstoday.com/articles/325803.php?utm_source=newsletter&utm_medium=email&utm_country=US&utm_hcp=no&utm_campaign=MNT%20Daily%20Full%20%28non-HCP%20US%29%20-%20OLD%20STYLE%202019-07-19&utm_term=MNT%20Daily%20News%20%28non-HCP%20US%29

FC residents fight against Parkinson’s disease with boxing class

 July 19, 2019    By Bart Moss

Parkinson’s disease, a neurodegenerative disorder usually associated with tremors and muscle rigidity, affects nearly one million people in the United States. Upwards of 60,000 new diagnoses of Parkinson’s are recorded each year, according to the Parkinson’s Foundation. Diagnosis is usually made via observation, and there is no known cure.

A few Franklin County residents have found a way to fight back against the disease, however, in what might seem a most unlikely way: boxing.

Rock Steady Boxing, a class in The Basement Gym owned by Jamie Poole in downtown Florence, is working to help people who suffer from Parkinson’s manage the symptoms of the disease – such as muscle rigidity, loss of balance, slowness of movement and postural instability.

“Rock Steady Boxing enables people with Parkinson’s disease to fight the disease by providing a non-contact boxing-style fitness program to improve their quality of life and sense of self-worth,” explained Gena Tsukashima, an occupational therapist and program coach. “We provide encouragement through a ‘tough love’ approach that inspires maximum effort, speed, strength, balance and flexibility.”

David Willis, a former teacher and coach in the Franklin County Schools system, was diagnosed with Parkinson’s disease in 2014, and he has experienced firsthand the benefit of Rock Steady Boxing.

“The class has helped me with my balance, strength and coordination,” said Willis. “I have also seen improvements in my handwriting.”

Gerald Hester, a senior vice-president with CB&S Bank, was diagnosed with Parkinson’s disease in 2017.

“This has been very good for me,” said Hester, who has been doing the class for six months. “It is hard work, but I can tell a big difference in just the little things like balance and coordination.”

Amy Moss, a teacher and coach at Phil Campbell High School, was diagnosed with early-onset Parkinson’s disease in 2016.

“I love going to the class,” said Moss. “I have developed a lot of friendships, and it has helped my confidence and has given me the encouragement to keep fighting every day.”

Willis agreed. “I like the camaraderie in the class with the other boxers … It has given me hope in delaying the progression of the disease.”

Parkinson’s disease was brought into the national spotlight by Family Ties and Back To The Future star Michael J. Fox and his foundation to find a cure for the disease

https://www.franklincountytimes.com/2019/07/19/fc-residents-fight-against-parkinsons-disease-with-boxing-class/

By Learning to Shift Perspective, We Can Change What’s Possible

JULY 19, 2019     BY DR. C 

I hate exercise! Both my pain and fatigue increase when I exercise. These are disabling Parkinson’s disease symptoms, and both trigger the fight-or-flight response that often manifests as “the grouch.” I have not found an easy way of exercising with Parkinson’s pain and fatigue, but I have found ways to shift my perspective. Shifting perspective opens up the possibility of experiencing enjoyment from exercise.

One of the most important parts of a Parkinson’s wellness map is exercise. But here’s the catch: It’s difficult to do with regularity. We know it works! Yet, knowing what is good for wellness is not the same as doing it. The doing part of exercise — showing up three to four times a week — is difficult with all the chronic disease barriers. It’s easy to feel defeated before even starting.

The way around this apparent Catch-22 is to shift one’s perspective on exercise. I mentioned the idea of shifting perspective in connection to wellness in a column about moments of well-being. The shift I need with regard to exercise is one that will get me off the sofa and into exercising. I am not getting off the sofa to do something I hate, but rather to do an enjoyable, creative project that involves exercise: landscaping to produce gardens. It’s a good exercise to keep the trunk strong, which helps prevent falls.

It takes a bit of perseverance to get into my work clothes, strap on the heavy work boots, find the hat and sunglasses, and then head out the door. Surveying the work ahead — which is sometimes a bit daunting — I start with light work to warm up. Walk, then shovel, and maybe rake, before getting behind the wheelbarrow to move gravel or dirt from one location to another. Pause to hear the birds sing, marvel at the variety of flower blooms and fragrances. Pretty quickly, the world slips away, replaced by the Zen of gardening.

My Fitbit reminds me when a time for medication is coming up and keeps track of my heart rate. I take lots of water breaks! By the time two hours have passed, my work shirt is drenched with sweat — as much as, if not more than, the amount of water I’ve consumed. In the Zen garden moments, the mind is free of the worries of Parkinson’s and vision problems. That feeling remains with me, not as a false euphoria, but as a deep-rooted sense of well-being.

There are many ways that shifting perspective can open wellness possibilities. A nurse shared a wonderful example. She was a smoker from her early teen years, and now in her 30s, she decided to quit. Six months without a smoke and she says, “I had this memory of how much I enjoyed smoking.” So, she bummed a cigarette and immediately got sick from smoking it. Recounting the event, she says, “I can remember the horrid feeling as clear today as if it just happened. I never had the urge to smoke again after that.” She shifted her perspective from enjoying smoking to thinking of it as a horrid, sickening experience. Shifting perspective opened up the possibility of wellness.

There is research supporting the practice of shifting perspective in a way that promotes well-being. The placebo effect is a mind/body interaction where the patient is convinced of treatment efficacy, which is a shift in perspective. Also, in many cases of “miracle” disease remission, a common theme is the patient’s ability to shift perspective. Reframing a problem can provide a new perspective and lead to new solutions.

The ability to shift perspective may also improve our ability to adapt to stressful times and to become more resilient, and therefore more open to new possibilities. The shifting of perspective causes us to shift our focus to a new intention, a new possibility. I hated exercise, and my intention was to avoid it. The shift in perspective offered the new intention of enjoyment and the possibility of a beautiful garden, along with a healthier body, in spite of the chronic disease limitations.

How has the ability to shift your perspective helped you? Please share your story in the comments below.

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

https://parkinsonsnewstoday.com/2019/07/19/shifting-perspective-changes-whats-possibile-well-being-exercise/

N-acetylcysteine Helps Ease Motor, Cognitive Problems in PD, Study Reports

 JULY 19, 2019    BY JOSE MARQUES LOPES, PHD

Treatment with the naturally occurring antioxidant N-acetylcysteine (NAC) along with standard Parkinson’s therapies improved patients’ motor and mental abilities, possibly by restoring the function of dopamine-producing nerve cells, according to new research.

The study, “N-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson’s Disease,” appeared in the journal Clinical Pharmacology & Therapeutics.

The progressive loss of dopamine-producing neurons and reduction in the brain levels of this neurotransmitter are well-known hallmarks of Parkinson’s. This degeneration is likely due to oxidative stress, an imbalance between the production and clearance of toxic free radicals called reactive oxygen species, which results in cellular damage.

Oxidative stress reduces the levels of glutathione, an antioxidant that prolongs cell viability. Also, the amount of this molecule in brain areas using dopamine — such as the substantia nigra, which is affected in Parkinson’s — is low, suggesting a reduced ability to defend against oxidative damage.

In a pilot study, a team at Thomas Jefferson University (TJU) in Pennsylvania had shown that three-month treatment with NAC — a precursor of glutathione, taken as an oral supplement and via intravenous (IV) delivery to prevent liver damage — may improve dopamine transporter (DAT) binding in people with Parkinson’s. Previous research had also shown that NAC may boost glutathione levels in platelets and lower the amounts of reactive oxygen species.

Aiming to extend these findings, the scientists tracked dopamine re-uptake into neurons using an imaging technique called SPECT coupled with a molecule called DaTscan, which enables visualization of dopamine transporter molecules. DaTscan had previously been used to link DAT binding with Parkinson’s disease severity.

Specifically, changes in nerve cell function were assessed in the caudate and the putamen, two important brain areas involved in motor control and with decreased DAT activity in Parkinson’s patients.

The study (NCT02445651) included 42 Parkinson’s patients, all able to continue standard-of-care treatment regimens. A group of 28 participants — 14 men and 14 women; mean age 62.4 years and mean disease duration 4.3 years — also received NAC for three months by two routes to help ensure consistent dosing: IV infusion (50mg/kg once per week) and orally (500 mg twice a day) between infusions.

At baseline, patients not taking the mainstay Parkinson’s medication levodopa had higher DAT binding levels. Also, having higher (worse) Unified Parkinson’s Disease Rating Scale(UPDRS) scores — a measure of cognitive and motor function — and longer disease duration were associated with lower DAT binding. UPDRS scores were higher with older age and were elevated in women compared to men.

Importantly, the results showed that adding NAC to the current treatment program led to 3.4–8.3% increases in DAT binding in both caudate and putamen. Also, the team found nearly 14% improvement in UPDRS scores, with similar changes in motor and non-motor components.

The results further showed that treatment with NAC improved serotonin transporter binding, recently suggested as a way to assess early changes in Parkinson’s.

“The results suggest NAC may positively affect the dopaminergic system in patients with PD, with corresponding positive clinical effects,” the researchers stated. “Larger-scale studies are warranted.”

Daniel Monti, MD, the study’s lead author, said in a press release that the study “is an important step in understanding how N-acetylcysteine might work as a potentially new avenue for managing Parkinson’s patients.” Monti, director of the Marcus Institute of Integrative Health at TJU, added that “NAC appears to enable dopamine neurons to recover some of their function.”

Andrew Newberg, MD, the study’s senior author and director of research at TJU’s Department of Integrative Medicine and Nutritional Sciences, said: “This is an exciting study that suggests a natural molecule such as NAC can help improve dopamine function and symptoms in Parkinson’s patients.”

https://parkinsonsnewstoday.com/2019/07/19/n-acetylcysteine-helps-ease-motor-cognitive-problems-in-pd-study-reports/

Gulf War Illness Linked to Higher Risk of Parkinson’s-like Symptoms, Study Finds

JULY 19, 2019     BY MARISA WEXLER IN NEWS.

Veterans of the Gulf War are not, as a whole, more likely to experience Parkinson’s disease-like symptoms, a new study has found. However, veterans with Gulf War illness do appear to be at greater risk of these symptoms.

The study, “Do Gulf War veterans with high levels of deployment-related exposures display symptoms suggestive of Parkinson’s disease?,” was published in the International Journal of Occupational Medicine and Environmental Health.

The Gulf War, which also is known as the Persian Gulf War or the First Gulf War, took place in 1991. Many people were exposed to toxic chemicals, including pesticides, smoke from oil well fires, and low levels of chemical warfare agents. This is suspected to be one of the causes of Gulf War illness (GWI), which affects as many as a third of Gulf War veterans and is characterized by persistent fatigue, pain, and problems with memory, concentration, and mood.

Interestingly, GWI and Parkinson’s disease share many features. Both have been linked to chemical exposures. Both are variable in how symptoms manifest. And, GWI symptoms resemble some non-motor symptoms of Parkinson’s (e.g., fatigue and mood problems). Yet, Parkinson’s has never been explicitly studied in veterans of the Gulf War.

In this study, 293 Gulf War veterans were recruited and given questionnaires that included questions about Parkinson’s-like symptoms, GWI symptoms, and exposure to chemicals during the war. The study participants were  predominantly white (72%) and male (84%), and most individuals had served in the army (57%).

A total of 122 (42%) people in the group had GWI disease as assessed by the Kansas Gulf War Military History and Health Questionnaire. Additionally, 231 (79%) veterans met the United States Centers for Disease Control and Prevention (CDC) criteria for “chronic multisymptom illness” (CMI), which is basically GWI but with less-stringent diagnostic criteria. Veterans who had neither were deemed “healthy” for the sake of the researchers’ analysis.

Veterans with GWI or CMI were less likely to have served as officers in the war, they were more likely to be ethnic minorities and to be younger and less-educated than their healthy peers.

Among the healthy veterans, there were no Parkinson’s-like motor symptoms, and few non-motor symptoms reported, which suggests that Gulf War deployment alone doesn’t increase the likelihood of developing these symptoms.

However, participants with GWI or CMI were significantly more likely to report Parkinson’s-like symptoms (both motor and non-motor) than their healthy peers.

Veterans with GWI or CMI also were more likely to have been exposed to more chemicals during the war, and more chemical exposure was associated with a greater likelihood of having non-motor Parkinson’s symptoms across the whole group. (Although this association wasn’t statistically significant among subgroups, for example, in people with GWI.)

Additionally, among all participants, those with Parkinson’s-like motor symptoms were more likely to report having seen their area “being sprayed or fogged with pesticides” compared to veterans without such motor symptoms.

The researchers also measured the size of 202 participants’ basal ganglia, a region of the brain that is implicated in Parkinson’s disease. Interestingly, having a smaller basal ganglia was statistically linked to a greater likelihood of having GWI or CMI, but it wasn’t linked to Parkinson’s-like symptoms or to wartime chemical exposures.

Some of the “muddiness” of this data likely comes from the inherent inaccuracy of relying on self-reporting and the difficulty of getting precise measurements about something like chemical exposure during a war. Additionally, it’s important to note that this study’s 293 participants are unlikely to be truly representative of the 700,000 or so United States Gulf War veterans.

“Although little is known about the long-term consequences of GWI, findings from this study suggest that veterans with GWI show more symptoms as those seen in [Parkinson’s]/prodromal [Parkinson’s], compared to healthy deployed GW veterans,” the researchers wrote.

However, they caution that “[b]ecause the present study did not clinically evaluate the veterans involved for [Parkinson’s], future studies will be necessary to determine if [GWI] and/or CMI cases truly are at increased risk of developing [Parkinson’s disease].”

https://parkinsonsnewstoday.com/2019/07/19/gulf-war-illness-higher-risk-parkinsons-symptoms/

Taking out the protein garbage becomes more difficult as neurons age

JULY 19, 2019   by Perelman School of Medicine at the University of Pennsylvania

Aberrantly formed autophagosomes accumulate in neuron of an aged mouse (Credit: Andrea Stavoe, Penn Medicine; eLife (A) Time series of GFP-LC3B in the distal axon of a DRG neuron from a young adult mouse. Green and white arrowheads each follow one autophagosome biogenesis event. Retrograde is to the right. Scale bar, 2 μm. (B) Quantification of the rate of autophagic vesicle (AV) biogenesis (assayed by GFP-LC3B puncta formation per minute) in DRG neurons from young (one mo, light green), young adult (three mo, green), aged (16–17 mo, dark green), and advanced aged (24 mo, very dark green) mice (mean ± SEM; n ≥ 54 neurons from three biological replicates). Credit: Andrea Stavoe, Penn Medicine; eLife

Cells dispose of harmful "trash" through autophagy, a normal and necessary process in which aggregated proteins and dysfunctional structures are handled. If any part of this fails, waste builds up inside cells, eventually killing them. According to a new study from the Perelman School of Medicine at the University of Pennsylvania, as cells age, their ability to shed harmful refuse declines. The findings suggest that the deterioration of autophagy in aged neurons—cells that never replicate and are as old as the bodies they inhabit—could be a risk factor for a suite of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), Alzheimer's, and Parkinson's.

Using live-cell imaging of neurons from young and aged mice, Erika Holzbaur, Ph.D., a professor of Physiology, and first author Andrea Stavoe, Ph.D., a postdoctoral fellow in Holzbaur's lab, published their study this week in eLife. The importance of autophagy was recognized in 2016 with the Nobel Prize in Physiology or Medicine.

"The current thinking among scientists is that a decline in autophagy makes neurons more vulnerable to genetic or environmental risks," Holzbaur said. "What motivates our line of research is that most neurodegenerative diseases in which a deterioration of autophagy has been implicated, such as ALS, and Alzheimer's, Huntington's and Parkinson's diseases, are also disorders of aging,"

At the start of autophagy, a component within the cell, called an autophagosome, engulfs misfolded proteins or damaged structures to be degraded, essentially sequestering this waste in a biological trash bag. The autophagosome then fuses with a second cellular structure, called a lysosome, that contains the enzymes needed to breakdown the garbage, allowing the components to be recycled and reused. This elegant waste-removal stream is what keeps neurons healthy, but in its absence, neurons eventually die due to the buildup of unattended refuse.

"Think city streets during a sanitation workers strike," Stavoe said.

The team assessed rates of autophagy in mouse neurons during aging and identified a significant decrease in the number of autophagosomes produced, along with pronounced defects in the structure of autophagosomes produced by neurons from aged mice.

While early stages of autophagosome formation were unaffected, they found frequent stalling in their formation in aged mice, while the ones that did form were misshapen. These defects may allow the trash to accumulate at neuronal synapses. Stavoe notes that in other studies autophagosomes with misformed membranes have been observed in deceased human brain tissue from donors with neurodegenerative disease.

Importantly, turning on the protein WIPI2B in aged mice restores autophagosome formation in aged neurons, bringing the autophagy garbage-hauling process back online. This rescue is dependent on the level of activation of WIPI2B, providing insight into the biological regulation of autophagosome formation.

On the other hand, when researchers took WIPI2B out of young neurons, autophagosome formation stalled. "This stunning and complete rescue of autophagy using one protein suggests a novel therapeutic target for age-associated neurodegeneration," Stavoe said.

More information: Andrea KH Stavoe et al. Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons, eLife (2019). DOI: 10.7554/eLife.44219

Journal information: eLife 

Provided by Perelman School of Medicine at the University of Pennsylvania 

https://medicalxpress.com/news/2019-07-protein-garbage-difficult-neurons-age.html