The Death of Self: A Casualty of Chronic Disease

death of self

Death, the “D” in the CHRONDI Creed, refers more to the death of our self-identity than it does to physical death. As we endure the long battle with a chronic disease and deal with a gradual progression in symptoms, a loss of function occurs. I touch upon the stealing away of bits and pieces of both physical and mental function in my column about the “disease thief.”

The disease thief robs us of so many of the ways by which we know ourselves. It is a death of the self that is a casualty of chronic disease. The death of self needs to be addressed with as much mindfulness as any other part of the creed for total health to be maintained at the highest level possible.

There is no manual for navigating through the death of self. I was educated in many ways to be prepared for it. And yet when it happened, I was shocked by the severity of its effects. Parkinson’s disease gradually took from me those things I identified as belonging to myself, things I would pull out of my pocket when someone asked, “What do you do?”

Following is a list of things that were stolen from me, roughly in chronological order:

  • Field mineral specimen collecting (since I was a teenager)
  • Professional field geologist
  • Hiking and exploring rugged terrain
  • Clinical counseling work
  • Professor of counseling and geology

The time and money spent on four college degrees are behind all the years of experience expressed in the above list. Now all are casualties of a chronic disease. It is the death of self.

Looking in the mirror, past the gray hair and crevasses of age, deep into multicolored eyes, I found nothing that I remembered as me. The self I once knew was gone — dead! I was sitting in a void in a life without meaning, with nothing of familiarity.

From my clinical work, I knew that people get lost when this happens. It can be quite difficult to find the way back. I also knew something about this journey from mystical teachings, but knowing and living through it personally are two different things. Somehow, I had to find my way out. I had to heal from the death of self.

We can apply stages of grief to healing from the death of self. As I mentioned in the disease thief column, we should use terror management should as needed. And it is important to have a support network through the process, including peers, family, and technology. Additionally, the CHRONDI Creed can be used to help with healing, particularly the “I” in Identity. I will cover that in the next column.

Have you experienced the “death of self” while battling a chronic disease? What progress have you made?

***

 

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.

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Motor Dysfunction Among Predictive Markers of Parkinson’s in People with Sleep Disorder, Study Reports

sleep disorder, Parkinson's risk

Mild cognitive impairment, motor and olfactory deficits, and erectile dysfunction are among the markers able to predict the development of Parkinson’s and associated disorders in people with rapid eye movement sleep behavior disorder, according to a large study.

The research was published in the article, “Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study,” in the journal Brain.

Disorders characterized by the aggregation of alpha-synuclein — such as Parkinson’s, dementia with Lewy bodies, and multiple system atrophy  — may all have an early period of more than 10 years that’s characterized by signs of neurodegeneration, but without full clinical disease.

Unlike most markers of this early — or prodromal — period, rapid eye movement sleep behavior disorder (RBD) has been specifically linked to the development of synuclein-related diseases. RBD of no known cause, or idiopathic RBD (iRBD), occurs in approximately 1% of people older than 60, and usually converts to Parkinson’s or related disorders over a decade or more. This means that 1% of the elderly population have an identifiable but often undetected early-stage neurodegenerative syndrome.

As most studies on predictors of these parkinsonism diseases had been single-center, a team at The Neuro — Montreal Neurological Institute and Hospital — and the Montreal General Hospital of the McGill University Health Centre combined the research experience of 24 centers in North America, Europe, Seoul, and Sydney, which participated in the International RBD Study Group, to measure the risk of developing such disorders and test 21 potential predictors.

At the beginning of the study, a total of 1,280 participants (average age of 66.3 years, and 82.5% men) with iRBD but without parkinsonism or dementia underwent a variety of tests to assess sleep disturbances, motor function, cognition, depression, anxiety, olfaction, and autonomic function. The patients were then followed for up to 19 years. According to the team, this was “the largest study ever performed in iRBD.”

Over a mean period of 4.6 years, 352 patients (28%, with a mean age of 67.6 years) acquired an overt neurodegenerative syndrome, which corresponded to an annual rate of 6.25%. The risk of developing such diseases progressively increased from 10.6% after two years to 73.5% after 12 years. Among these 352 patients, 199 first showed signs of parkinsonism, while 153 developed dementia first.

Then the analysis revealed that motor dysfunction — as assessed through different measures — olfactory deficit, mild cognitive impairment, erectile dysfunction, an abnormal dopamine transporter (DAT) scan, color vision impairment, constipation, REM sleep without muscle atonia (reduced strength), and older age significantly predicted neurodegenerative disease development.

DAT is responsible for the uptake of dopamine — the neurotransmitter found in lower levels in people with Parkinson’s — into nerve cells.

In contrast, sex, insomnia, daytime sleepiness, restless legs syndrome, sleep apnea, urinary dysfunction, and depression or anxiety were not significant predictors.

Only those predictive markers that tested cognition and quantitative motor function differentiated the people who first developed dementia from those first showing signs of parkinsonism. These assessments of quantitative motor function were simple office-based tests that took less than five minutes.

“Clearly these are strong candidates for selecting patients for future neuroprotective trials, and could even obviate the need for sophisticated imaging techniques,” the investigators wrote.

“We confirmed a very high risk of (Parkinson’s) in people with REM sleep disorder and found several strong predictors of this progression,” Ron Postuma, the study’s lead author, said in a press release. “As new disease-modifying treatments are being developed for (Parkinson’s) and related diseases, these patients are ideal candidates for neuroprotective trials.”

A separate analysis estimated that 366 patients per experimental group would need to be recruited into a two-year trial for a therapy to reduce in half the incidence of RBD converting to parkinsonism or dementia. Increasing the trial duration or assuming a greater reduction in disease development led to lower estimates for the number of patients required. Also, this analysis showed that using different predictive markers to classify patients would significantly alter the number of patients required for clinical trials.

“Of course, exact sample size calculations will depend on the specifics of a clinical trial; nevertheless, the fact that 24 centers combined to produce these estimates can provide some confidence for trial planners that sample sizes will be representative of the global experience,” the study stated. “Notably, the total sample size for a future neuroprotective trial is less than the number of participants who were recruited to this study.”

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Grant Will Enable Pharmacologist to Expand Gaucher Disease Research to Parkinson’s

pharmacologist

As it sometimes happens in rare-disease research, a prospective therapy for one disorder has potential to help another. So it is that, at Temple University, molecular pharmacologist Marlene Jacobson, PhD, has been awarded a joint grant to explore how a discovery could affect Parkinson’s disease (PD) patients.

Specifically, The Michael J. Fox Foundation (MJFF) and The Silverstein Foundation for Parkinson’s with GBA want Jacobson to further study compounds that she found could reverse Gaucher disease Type 2, the most severe form of the lysosomal storage disorder caused by deficiencies in the glucocerbrosidase (GCase) protein due to mutations in the GBA1 gene.

Some 10 percent of PD patients carry the same mutation, making it the most common genetic disease risk. GCase allows brain cells to clear debris via lysosomes, which are special compartments within cells that digest and recycle different types of molecules. Patients with reductions in GCase activity can’t effectively remove debris, which scientists widely hypothesize is toxic to brain cells.

“I came to Temple because I wanted to make a difference in patients’ lives,” said Jacobson in a press release. “I wanted to use my drug discovery skills and apply them to help patients who are underserved.”

An associate professor of pharmacodynamics in Temple’s Department of Pharmaceutical Sciences, and associate director of its Moulder Center for Drug Discovery Research, Jacobson will expand her Gaucher research to include PD patient cells that have the GBA1 mutation. She joined Temple six years ago after 24 years in research and drug discovery for Merck Research Laboratories.

”The key is we have the full disease environment in the cell,” said Jacobson. “We’re very fortunate to have access to these patient cells, and we treat them with respect as they provide an advantage in demonstrating a compound’s potential to reverse a disease state.”

Parkinson’s patients with the GBA mutation develop the disease at an earlier age, she said, and their cognition symptoms are worse relative to patients without the mutation.

”The link between mutations in Gaucher disease and Parkinson’s disease suggests a common disrupted mechanism or pathway. We can translate the compounds we have found to improve Gaucher and Parkinson’s.”

Currently, there is no effective treatment for Gaucher disease Type 2. In Parkinson’s, available therapies are focused on raising dopamine levels in patients’ brains, or on controlling the symptoms themselves.

“This work is so exciting and so primed for discovery,” Jacobson said, adding that the pharmaceutical industry is increasingly looking to academic investigators for breakthrough ideas leading to new treatments.

The amount of the grant was not disclosed.

The MJFF aims to find a cure for Parkinson’s through an aggressively funded research agenda, and to help develop improved therapies for current patients. The Silverstein Foundation is focused on finding ways to prevent the onset of Parkinson’s in GBA-mutation carriers.

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Hydrotherapy Improves Balance, Mobility in Parkinson’s Patients, Study Reports

hydrotherapy

Hydrotherapy may provide significant balance and mobility benefits in patients with Parkinson’s disease compared to medication and land-based exercises, according to a review study.

The research, “The Effects of Hydrotherapy on Balance, Functional Mobility, Motor Status, and Quality of Life in Patients with Parkinson Disease: A Systematic Review and Meta-analysis,” was published in the journal PM&R.

Impairments such as muscle rigidity and tremor affect the balance and mobility of people with Parkinson’s. Combined with fear of falling, it promotes a sedentary lifestyle and reduces quality of life.

Water-based exercise is often prescribed to these patients, providing a safe environment that reduces the risk of falling. Prior studies have reported that hydrotherapy improves motor symptoms. However, the evidence about  hydrotherapy as a treatment strategy in Parkinson’s is scarce.

To address this gap, researchers conducted a systematic review of the available scientific literature and a meta-analysis — a type of statistical analysis that combines the results of various studies.

The scientists focused on hydrotherapy’s effectiveness on patients’ balance, mobility, quality of life and motor function.

For this purpose, the investigators searched seven online databases as well as unpublished or ongoing clinical trials from inception through December 2017. Nineteen studies were identified, of which eight were randomized controlled trials (RCTs). Overall, the studies had 484 participants, with a mean age ranging from 54 to 78 years and an average disease duration ranging from three to 10 years.

The studies had different designs, which included comparisons of hydrotherapy with land-based exercises or medications, combinations of hydrotherapy with land-based therapy, and assessments of low-intensity and muscular resistance water-based exercises.

Hydrotherapy could include balance training, stretching, strengthening, trunk mobility, and gait exercises. The sessions ranged from 40 to 60 minutes, one to five days per week, for three to 20 weeks, for a total of eight to 60 sessions. Water temperature was set between 28ºC (82ºF) and 34ºC (93ºF) in the 12 studies that reported this parameter.

All but two studies with available information on levodopa usage evaluated patients’ in the “on” phase, which refers to the period when this medication is effective and has not yet worn off.

The meta-analysis on balance and mobility included five RCTs, which had a total of 133 patients. The results showed that hydrotherapy with or without land-based exercises significantly improved both balance and mobility compared to land-based therapy or usual care with medication alone.

Three other studies not included in the meta-analysis due to lacking a control group also found significant benefits with hydrotherapy in balance. One RCT not included in the statistical comparison did not report differences with hydrotherapy and land-based therapy, while another showed that aquatic obstacles training is more beneficial for balance than traditional water-based exercises.

In turn, two RCTs not included in the respective analysis failed to show mobility improvements with hydrotherapy.

As for quality of life, an analysis of three RCTs with 76 patients showed no benefits with hydrotherapy compared to land-based treatment, which the researchers attributed to the small number of studies included. This also was observed in one RCT not included in the meta-analysis. In contrast, five other studies, including two non-randomized trials, found significant improvements with water-based treatment.

Results of a meta-analysis of five RCTs with 140 patients also did not reveal improvements in motor function in comparison to land-based exercise. This can be explained by patients having types of motor complications not expected to improve with hydrotherapy, the team said.

Of note, two other RCTs and a non-randomized trial also did not find different results with hydrotherapy compared to other approaches in motor function.

Overall, the scientists wrote, “hydrotherapy, combined or not with other therapies, may improve balance and functional mobility of patients with [Parkinson’s] when compared to land-based therapy alone or usual care.”

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ProMIS to Present Data on Potential of Antibodies to Target Toxic Alpha-Synuclein in Parkinson’s

ProMIS Neurosciences antibodies

ProMIS Neurosciences will present evidence of the selectivity of several of its antibody candidates to target the toxic forms of alpha-synuclein, a key component of Lewy bodies that underlie the development of Parkinson’s disease.

Neil Cashman, PhD, chief scientific officer of ProMIS, will present the study, “Targeting of Pathogenic Aggregated Alpha-Synuclein: Refining Antibody Epitopes by Design,” at the 14th​ International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders, taking place March 26–31 in Lisbon, Portugal.

In Parkinson’s disease, alpha-synuclein’s 3D structure is abnormal, or misfolded, promoting its aggregation into clumps and causing the death of dopamine-producing nerve cells — those responsible for releasing the neurotransmitter dopamine, which is critical for regulating brain cell activity and function.

ProMIS Neurosciences developed a technology to design antibody candidates that bind only to the toxic forms of misfolded proteins like alpha-synuclein.

This means that healthy alpha-synuclein proteins are left alone, allowing the protein to function normally inside the cells — alpha-synuclein plays a key role in the healthy brain, regulating the release of synaptic vesicles, “bubbles,” filled with chemical neurotransmitters (chemical messengers). The synapse is the junction between two nerve cells that allows them to communicate.

This regulation occurs when alpha-synuclein is in its healthy state, i.e., arranged in a tetramer — four units of the protein wrapped around each other.

In lab studies, the antibody candidates were able to protect rodent neurons against the toxicity of alpha-synuclein and inhibited the mechanisms involved in the protein’s propagation.

ProMIS Neurosciences’ lead antibody candidate, PMN310, is a potential treatment for Alzheimer’s disease, and was shown to attack only toxic forms of a protein linked to the disease — amyloid-beta — and not normal forms. This investigational therapy is expected to enter Phase 1 clinical trials in 2019.

“The ability to bind toxic forms and only the toxic forms of misfolded proteins in the brain has been a frustratingly elusive challenge in both Parkinson’s and Alzheimer’s drug development,” Cashman said in a press release. “This is largely because the toxic species of the affected proteins still share many similarities with the healthy forms of the protein, making them impossible to target with precision using traditional tools for developing antibodies.”

“Using our unique discovery platform, we have been able to successfully address this problem. Our data show we can raise antibodies that bind the toxic species and only the toxic species of alpha-synuclein with exquisite precision while preserving the healthy forms of the protein,” he added.

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The Parkinson Association of Alabama announces 2019 Taste For a Cure

The Parkinson Association of Alabama (PAA) is thrilled to announce that Taste for a Cure 2019, presented by the Ernest G. DeBakey Charitable Foundation, is Thursday, April 11 at 6:00 PM. Join us at Haven on World Parkinson’s Day for another great evening of:

  • Unique food, beer, wine and cocktail pairing conceived and prepared by an all-star team of local chefs from these restaurants: READ MORE…

Trunk Exercises May Improve Balance in Parkinson’s Disease, Study Finds

Falls and Parkinson's

Exercise and fall prevention education can improve front-to-back trunk mobility in Parkinson’s patients with a history of falls, according to a Phase 2 clinical trial.

The study, “Trunk exercises improve gait symmetry in Parkinson disease: A blind phase II randomized-controlled trial” was published in the American Journal of Physical Medicine & Rehabilitation.

People with Parkinson’s disease are twice as likely to fall as those with other neurological disorders. Previous studies suggest that Parkinson’s patients underestimate the muscle work needed to produce a certain movement.  This lack of motor and perceptual ability leads them to adopt distinct postural strategies to keep their balance, both during static and dynamic movements.

Studies have associated falls to deficits in step-to-step symmetry and trunk muscle function.

Although antiparkinsonian medications can help control Parkinson’s motor symptoms as the disease progresses, patients typically need to gradually increase the treatment dose for maximum benefit. Even after increasing the dose, they might sometimes experience a reappearance or worsening of symptoms due to the diminishing effects of the therapy.

Therefore, there is a need for non-pharmacological therapies that alleviate patients’ motor symptoms and improve their quality of life.

Australian Catholic University researchers set up to investigate whether an exercise program geared to improving the strength and endurance of the trunk muscles could improve standing and walking balance in those with Parkinson’s disease.

The Phase 2 study (ACTRN12613001175763), evaluated 22 Parkinson’s patients (15 men and seven women, mean age 65.4 years) with a history of falls who were randomly assigned to either 12-weeks of exercise and fall prevention education (11 participants) or fall prevention education alone (11 participants).

For the exercise intervention, patients had to attend a supervised 90-minute training session once a week for 12 weeks. Each session was conducted in groups of up to three subjects.

“In short, the exercise-based intervention comprised three parts; i) a warm-up focusing on trunk mobility exercises to improve range of motion; ii) an exercise routine focusing on the endurance and stability of the trunk muscles …; and iii) a cool-down involving stretching and walking in a real-world environment,” researchers stated.

The exercise group also received health advice (same as the education-only group), in the form of weekly educational brochures, aimed at preventing falls.

Participants in the education-only group were encouraged to continue their day-to-day lives, but received a weekly multidisciplinary health tip for 12 weeks that explained how exercise, nutrition and/or sleep quality could influence their fall risk and quality of life.

Initial assessment showed that there were no differences in cognition, vision, neurological function and mobility between study groups. Nonetheless, the exercise sample had a greater body mass index (measure of body fat based on height and weight) compared to the education-only group.

Twelve and 24 weeks after initial assessment, investigators examined patients’ symptom severity, balance confidence, mobility and quality of life.

All 22 patients were reassessed at 12 weeks, but four subjects (two in the exercise group and two in the education-only group) did not complete the 24-week follow-up.

At 12 weeks, the exercise sample had significant and clinically relevant improvements in front-to-back step-to-step symmetry of head and trunk movements, meaning these patients might be able to balance themselves more easily. The exercise group also had improved trunk muscle function.

The education-only group also had significant and clinically relevant improvements but in side-to-side and vertical step-to-step trunk symmetry, as measured by the harmonic ratio — a mathematical analysis of trunk acceleration used to measure walking smoothness, walking rhythmicity, or dynamic stability.

Step-to-step symmetry remained unchanged from the 12- to the 24-week evaluation in the exercise group. “The lack of significant changes in step-to-step symmetry between the 12- and 24-week assessments for the exercise group also suggests that the benefits of the weekly exercise program may be retained for up to 12 weeks following the cessation of the training regimen,” researchers said.

Regarding the education-only sample, their reduced step-to-step trunk symmetry at 12 weeks had almost been restored to initial assessment (baseline) values at 24 weeks.

These results indicate that torso-specific exercises may improve (or at the very least, maintain) trunk mobility in Parkinson’s patients and that measures of step-to-step symmetry, such as the harmonic ratio, could be used to assess subtle changes in postural control.

“Given the encouraging outcomes of this study, future research might seek to establish whether increasing the frequency of this exercise program offers greater improvements in step-to-step symmetry and/or has the potential to reduce the rate of falls in people with [Parkinson’s disease],” researchers said.

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Don’t Give Up on This Bittersweet Journey

give up

Sherri Journeying Through

Everything’s not all right or OK. Like it or not, we have a chronic disease that won’t go away. Our days are consumed with uncontrollable thoughts; they ravage our minds, threaten our souls, and grasp for our spirits.

Will we ever be “us” again — those beings who once dwelled inside these bodies? Will we become the burden we think others perceive us to be or that we believe ourselves to be? Will we pout and feel sorry for ourselves, thinking our lives are nearly done when not long ago, it seemed that they were just beginning?

We need to find a way to view our circumstances with new eyes. To realize that our situation may actually be a blessing instead of a curse. We can choose to travel this bittersweet journey that’s been laid at our feet.

Remaining positive despite this disease can be extremely challenging. We must remind ourselves that things could be worse and be thankful for what we have. 

We can consider what we can still accomplish. Adopting a fresh perspective helps us to get through each day instead of wallowing in “what could have been.”

Once in a while, someone will say something to us that should have been left unsaid; words they deemed wise yet when spoken aloud came across as ignorant, inappropriate, or distasteful. Incorrect and inadequate information about Parkinson’s disease leads to foolish comments. We can feel defensive and sad at the remarks we hear. Or we can put on our masked smiles and let them think they know better when in reality, we know best.

These are the facts of having Parkinson’s: We shuffle when we walk, we choke when we eat, we drool on our pillows. We shake on the outside and the inside. Sometimes it feels as if we are going to come right out of our skins. Our toes curl and cramp, our fingers as well, and sometimes we wonder if we will ever feel normal again. “Normal” becomes a distant world.

We experience stiffness on the left side and rigidity on the right, along with intense pain. 

We grieve for things gained and lost. Depression vies for our attention; even as we try to push it back into its place, it seeks to control by beckoning, mocking, and screaming out our names.

Our speech may be soft or so slurred that others strain to hear our words. We are interrupted, cut off, and misunderstood. We feel as if we have nothing worthwhile to contribute to conversations, which in turn leaves us feeling insignificant.

However, despite our “abnormalities,” and mixed-up and out-of-control feelings, we cannot, and will not, quit. Quit is a four-letter word, as foul as those others are when used in conjunction with the unrelenting challenge of finding a cure. If we quit, we give up. We relinquish control to this disease. And that is something we must — as long as it is within our power — never, ever do.

***

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.

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Alpha-Synuclein Impairs ClpP Enzyme, Causing Mitochondrial Damage, Study Says

ClpP, mitochondrial damage

Alpha-synuclein reduces the levels and impairs the function of ATP-dependent Clp protease (ClpP), an enzyme found in mitochondria — the cell compartments responsible for the production of energy — causing mitochondrial damage and oxidative stress, a study shows.

The study, “Alpha-synuclein suppresses mitochondrial protease ClpP to trigger mitochondrial oxidative damage and neurotoxicity,” was published in Acta Neuropathologica.

Parkinson’s disease mainly results from the gradual loss of dopaminergic neurons in the substantia nigra, a region of the brain responsible for movement control.

The disease also seems to be associated with overproduction of the protein alpha-synuclein in nerve cells of the brain. When this protein clumps together, it gives rise to small toxic deposits inside brain cells, inflicting damage and eventually killing them. Besides the accumulation of alpha-synuclein, Parkinson’s disease has also been linked to mitochondrial dysfunction.

Previous studies have shown that alpha-synuclein, in particular its A53T mutant form, accumulates in mitochondria, progressively causing mitochondrial damage. However, the mechanisms by which alpha-synuclein and mitochondrial proteins interact and regulate each other during this process are not fully understood.

ClpP, a mitochondrial enzyme that breaks down proteins (protease), is important for maintaining healthy mitochondria. In addition, ClpP dysfunctions have been associated with neurodegenerative diseases, suggesting that this enzyme might be one of the missing links that could explain the relationship between alpha-synuclein and mitochondria dysfunction in Parkinson’s disease.

To explore this idea, a group of researchers from the Case Western Reserve University School of Medicine and their collaborators set out to investigate if and how alpha-synuclein and its A53T mutant form affected the levels and function of ClpP in neurons isolated from patients with Parkinson’s and in animal models of disease.

Researchers showed that the levels of ClpP dropped significantly in the presence of high levels of alpha-synuclein. This was true for neurons derived from patients’ induced pluripotent stem cells (iPSCs), in dopamine-producing neurons isolated from mice genetically engineered to produce the A53T mutant form of alpha-synuclein and in postmortem brain samples from patients. iPSCs are fully matured cells that are reprogrammed back to a stem cell state, where they are able to grow into almost any type of cell.

On the other hand, a strong reduction in the levels of ClpP led to an overproduction of abnormal misfolded mitochondrial proteins, a reduction in mitochondrial activity, and increase in oxidative stress and cell death. Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them, resulting in cellular damage as a consequence of high levels of oxidant molecules.

Interestingly, forcing the production of ClpP successfully reduced oxidative stress associated with alpha-synuclein and prevented the accumulation of phosphorylated alpha-synuclein in neurons derived from iPSCs of patients carrying the alpha-synuclein A53T mutant.

Phosphorylation is a chemical modification in which a phosphate group is added to the protein. Alpha-synuclein phosphorylation is known to occur in Parkinson’s disease, and is thought to be a critical step in disease progression as it enhances alpha-synuclein’s toxicity — possibly by increasing the formation of alpha-synuclein aggregates.

In addition, investigators found that both the normal and A53T mutant forms of alpha-synuclein physically interacted with ClpP, blocking its activity. Remarkably, when researchers induced the production of an artificial form of ClpP in the brains of mice that produced the A53T mutant form of alpha-synuclein, they managed to prevent mitochondrial damage and oxidative stress, and to slow disease progression and behavioral impairments.

“In this study, we have identified, for the first time, an important role of mitochondrial matrix protease ClpP in [alpha-synuclein]-associated neuropathology [in Parkinson’s disease]. Thus, our findings should stimulate the development of ClpP modulators as potential disease-modifying therapeutic agents in [Parkinson’s disease] and other synucleinopathies,” the researchers concluded.

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Proper Nutrition May Prevent More Severe Motor Problems in Parkinson’s, Study Suggests

Parkinson's motor symptoms

Maintaining good nutritional status may protect Parkinson’s patients from greater motor impairments associated with weight loss, according to new research.

The study, “Untangling the relationship between fat distribution, nutritional status and Parkinson’s disease severity,” was published in the journal Aging Clinical and Experimental Research.

Prior research has reported that individuals with Parkinson’s experience weight gain and obesity at early stages of the disease, but weight loss and low body mass index (BMI) at later stages.

Malnutrition may be a contributing factor for weight loss in Parkinson’s, as a significant proportion of these patients are at risk of developing an inadequate nutritional status. Malnutrition may aggravate motor symptoms, which then may be associated with other complications, such as depression or cognitive decline.

A team of international researchers explored the link between Parkinson’s severity and obesity, focusing on whether excess fat was deposited at the hip and thigh areas (gynoid), or at the abdominal region (android). The investigators also assessed if nutritional status might alter the association between disease severity and fat distribution.

A total of 195 Parkinson’s patients (mean age 73.6, 124 men) were included, all admitted to a geriatric day hospital in Rome from January 2012 to December 2015. The participants underwent dual-energy X-ray absorptiometry to assess body composition, as well as determinations of body weight, height, and BMI.

Total abdominal and gynoid fat were evaluated, as were patients’ nutritional status, severity of motor symptoms, cognition, functional ability, and depressive symptoms.

The findings revealed that patients with better motor function were more likely men, more educated and had better cognitive function, mood, functional status, and nutritional status. Also, improved motor scores (as determined by the Unified Parkinson’s Disease Rating Scale part III ((UPDRS III)) correlated with higher total body fat, percentage of abdominal fat, trunk-leg and trunk-limb fat ratios, as well as abdominal-gynoid fat ratio.

However, after accounting for nutritional status, only the percentage of abdominal fat and trunk-leg fat ratio were still associated with UPDRS III scores. Further analysis revealed that a greater abdominal fat distribution was linked with less severe motor impairment, but only with patients with a Mini-Nutritional Assessment score lower than 23.5, which indicates risk for malnutrition or overt malnutrition.

“In other words, a good nutritional status might protect [Parkinson’s] patients from weight loss associated with disease severity,” researchers wrote.

At the same time, higher percentage of gynoid fat was associated with worse motor function in patients with a MNA score not lower than 23.5.

“The main result of our study is that nutritional status drives the association between total and regional adiposity [fat storage] and disease severity in Parkinson’s disease patients,” the team commented. “In this regard, the early detection of malnutrition or risk of malnutrition in subjects with [Parkinson’s] is warranted.”

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