New Study Reveals Molecular Signs of Parkinson's Disease

Parkinson’s Disease is a widespread chronic health issue that causes the degeneration of the central nervous system, which severely affects motor functions over time in addition to causing a number of other symptoms, including cognitive impairment, depression, fatigue, and sleeping problems. This disease is unfortunately fatal and causes a gradual degradation of the body and mind, though most of the symptoms can be managed and staved off by taking the right combination of medicine and possibly surgery.

While there is much information available about the treatments and symptoms of this disease in both its early stages and more advanced stages, the cause of Parkinson’s and it’s molecular structure have only just begun to be understood in this recent study.

 The Development of Parkinson’s Disease

Parkinson’s Disease is identified by the gradual degeneration of the central nervous system causing muscle rigidity, slow movements, and imbalance. The development of this disease is closely related to the production of neurons, neurotransmitters, and hormones that play a major role in motor functions.

The main chemical produced by the brain that contributes to motor function is dopamine, so when the nerve endings that produce dopamine become impaired or die, the motor system suffers and steadily degrades. Another set of neurotransmitters that become impaired in a person suffering from Parkinson’s disease are the nerve-endings that produce norepinephrine.

This particular chemical is one of the main messengers of the nervous system, controlling automatic bodily functions like blood pressure, heart rate, and digestion. It is largely the death and impairment of these neurotransmitters that lead to various progressive symptoms of Parkinson’s. However, the exact cause of neuronal failure remains unknown.

Parkinson’s disease affects nearly 500,000 people, and those numbers are, sadly, on the rise. While 90% of patients diagnosed are above the age of 60, the remaining 10% are within the 21-50 age bracket. It is these early cases that create the most worry, and at the same time, they show the most potential for identifying the molecular changes to the body that occur at the earliest stages of Parkinson’s disease.

What the Study Revealed

The study, published on 27th January 2020 in the journal Nature Medicine, was focused on the symptoms and development of the disease in young patients between the ages of 21 and 50. The study was conducted by a team of researchers from Cedars-Sinai and UCLA, and it first began by harvesting and generating special stem cells from young patients suffering from Parkinson’s. These stem cells are called induced pluripotent stem cells (iPSCs for short), and they are created by turning back the clock on adult cells by turning them into primitive embryonic cells.

These embryonic cells, iPSCs, can then produce genetically identical cells, replicating any type of cell in the human body. Using the iPSCs, the dopamine neurons of early-onset Parkinson’s patients were replicated, cultured in a dish, and analyzed. The goal, according to the senior author of the study Dr. Clive Svendsen, was to take the cells back to the earliest stages of their development and observe these dopamine neurons in the earliest stages of the disease, prior to major impairments.

Two major observations were detected. The first was a build-up of a protein commonly found in forms of Parkinson’s disease called alpha-synuclein in the neurons. The second observation was the malfunctioning of a number of lysosomes. Lysosomes are tiny sacs of enzymes in the cell that aid in digestion by acting as waste disposal systems, or “trash can” organelles that break down and dispose of proteins.

It could, therefore, be reasonably assumed that when the malfunctioning of these lysosomes occurs, it results in the accumulation of the alpha-synuclein protein in neuronal cells.

This technique and these observations show the first signs of early-onset Parkinson’s, which would likely imply that the build-up of alpha-synuclein over 2 or 3 decades could cause the progression of the symptoms of the disease. The greater the accumulation, the more severe the symptoms.
 
A Great Sign of Progress
These abnormalities are now being studied to determine their presence in other forms of Parkinson’s disease. The technique described in this study not only provided the team of researchers a method that helps us understand the progression of the disease on a molecular level, but also a means of drug testing.

The iPSCs were used to test a variety of drugs, one of which was found to reduce the high levels of alpha-synuclein. This drug, PEP005, was tested in both the dopamine neurons in the dish, as well as in lab mice, and was found to reduce alpha-synuclein levels. The benefit of this drug is that it has already been approved by the FDA (United States Food and Drug Administration) as a treatment for precancerous tumors of the skin.  

An additional surprising result of using the drug, PEP005, is an abnormal increase in the levels of an active protein called kinase C. However, the relation of this protein to Parkinson’s disease is still undiscovered. Experiments are being conducted to determine how the drug PEP005 might be used to treat or even prevent early-onset symptoms of Parkinson’s.

What Makes This Research So Important
Recent Study Uses Special type of stem cells to discover early signs of Parkinson's disease at younger ages


Dr. Michele Tagliati, professor and vice-chair of the Department of Neurology at Cedars-Sinai, director of the Movement Disorders Program and a co-author of the study stated that “Young-onset Parkinson's is especially heartbreaking because it strikes people at the prime of life… This exciting new research provides hope that one day, we may be able to detect and take early action to prevent this disease in at-risk individuals."

This study shows great potential for the future of Parkinson’s disease and in the discovery of possible preventive measures, treatments, and cures. This joint effort between Cedars-Sinai and UCLA also marks an important milestone in collective medical advancement.

As Dr. Shlomo Melmed of Cedars-Sinai said, “This research is an outstanding example of how physicians and investigators from different disciplines join forces to produce translational science with the potential to help patients.” This study marks one of many incredible collaborative programs from the past and hopefully for the future on Parkinson’s Disease. 

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Women who quit alcohol improve mental health ‘within four years’

LIFETIME non-drinkers are less likely to experience mental health problems, according to a study which also found that women benefit more than men from quitting alcohol. 

Researchers found that within four years of giving up alcohol, women had had experienced an improvement in their mental well-being that put them on a par with people who had always abstained. 

They said their findings “suggest caution in recommending that moderate drinking could improve health-related quality of life”. 

They add: “Instead, quitting drinking may be associated with a more favourable change in mental well-being, approaching the level of lifetime abstainers.

“This may be analogous to smoking cessation, which results in the recovery of health outcomes to the level of lifetime non-smokers.” 

Surge in Buckfast sales blamed on minimum pricing ‘trade-off’
 
The study, compared teetotalers with moderate consumers of alcohol in both US and Hong Kong populations. 

Moderate drinking was considered 14 drinks or fewer per week for men, and seven drinks or fewer per week for women. 

Heavy drinkers and binge drinkers were excluded from the study. 

It comes at a time when more adults in Scotland are giving up alcohol, and the overall intake of alcohol in 2018 was at a record low – coinciding with the introduction of Scotland’s minimum pricing law. 

Similarly, alcohol consumption among teenagers is at an all-time low. 

However, among adults in Scotland who do drink, the majority are still exceeding recommended guidelines – averaging 19 units per week, compared to the 14 unit maximum advised by Government. 

Alcohol sales in Scotland ‘lowest since records began’ as minimum pricing introduced
The sample size for the study was just under 41,500 participants – around 10,400 from Hong Kong and 31,000 from the US. 

Those who had never consumed alcohol scored the highest level of mental well-being at the start of the five-year analysis. 

For female drinkers, quitting was linked to a favourable change in mental health in both the Hong Kong and US populations. 

The authors state: “We found that lifetime alcohol abstainers reported the highest level of mental well-being. 

“Women who quit drinking were found to have a greater improvement in mental well-being than lifetime abstainers. This association was found in a Hong Kong cohort as well as in a US cohort. 

“On average, the mental well-being of female quitters approached the level of lifetime abstainers within a four-year period in both cohorts. 

“In contrast, initiation and persistent moderate drinking for four years were not associated with better mental or physical well-being.” 

Three bottles of wine ‘like 23 cigarettes’ by cancer risk
The results remained consistent even after the researchers adjusted for differences in socio-demographic characteristics, BMI, smoking status, self-reported diseases and physical activity.
However they added that it was unclear whether the change experienced by women actually has a physiological basis. 

They added: “The explanation for our findings and the underlying mechanism are not clear. It is possible that alcohol-related neurotoxicity reverses following abstinence. 

“Alcohol cessation may also reduce stressful life events, such as conflict within family, difficulties in employment and legal troubles, resulting in improved mental well-being. 

“It is also possible that improved mental well-being may result from the psychological benefits of ‘giving up’ per se rather than an effect of alcohol, as most Chinese women in Hong Kong use alcohol fewer than four times per month, which may not have a physiologic effect.” 

The findings will raise further questions over what is a safe and sensible amount to drink.
Another study last year said regularly drinking more than recommended limits is as bad for health as smoking. 

They estimated a 40-year-old drinking two pints or glasses of wine a day above guidelines can expect to die two years early and was associated with a higher risk of stroke, fatal aneurysm and heart failure. 

A brain scientist and co-author of the study, said: “Global alcohol consumption is expected to continue to increase unless effective strategies are employed. Our findings suggest caution in recommendations that moderate drinking could improve health-related quality of life. 

“Instead, quitting drinking may be associated with a more favourable change in mental well-being, approaching the level of lifetime abstainers.” 

Another person said: “We know that regularly drinking above the Chief Medical Officer’s low-risk guidelines can lead to mental health problems like anxiety and depression. Many people also use alcohol to relax and combat the feelings of stress, but the negative effects of alcohol are actually likely to make stress worse. 

“By cutting down on how much we drink we can reduce the risk of developing mental health problems as well as around 60 other diseases including liver disease, heart disease and alcohol-related cancers. 

“However, it can be difficult to always make the healthy choice when alcohol is available anytime, anywhere and we’re encouraged to drink in every social situation. Action on the price, availability and marketing of alcohol can help reduce consumption and protect health.” 

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Blood test can help diagnose pre-eclampsia

A simple blood test can help diagnose a common but potentially fatal pregnancy complication- pre-eclampsia, finds a study.

During the study, by measuring the concentration of placental growth factor (PIGF) in a woman's blood, doctors were able to diagnose pre-eclampsia 2 days sooner on average.

" We knew monitoring PIGF was an accurate way to help detect the condition but were unsure whether making this tool available to clinicians would lead to better care for women. Now we know that it does," said the lead author.

Pre-eclampsia, a condition in pregnancy characterised by high blood pressure, sometimes with fluid retention and proteinuria, can cause damage to vital organs, fits and can be fatal for the woman and baby, if left untreated. Globally, 100 women die due to pre-eclampsia every day.

" For the last 100 years, we've diagnosed pre-eclampsia by measuring blood pressure and checking for protein in a woman's urine. These are relatively imprecise and often quite subjective, he noted.

For the study, the research team studies 1,035 women with suspected pre-eclampsia from 11 maternity units across UK. They're randomly assigned to 2 groups= 1 had their PIGF test results made available to their clinical team, the other did not.

The PIGF testing was shown to reduce the average time to diagnose pre-eclampsia from 4-2 days and serious complications before birth ( such as eclampsia, stroke and maternal death) to 4 % from 5 %.

There was no change in the likelihood of complications for the baby, the age at which babies were delivered prematurely or whether they're admitted to a neonatal unit, the researchers said.

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Drinking Diet Drinks May Increase The Risk Of Strokes In Post-Menopausal Women

According to a recent study, it was found that drinking diet drinks could possibly increase the risk of having a stroke among post-menopausal women. Caused by a blocked artery, especially small arteries, stroke can turn out to be life-threatening. The association was found after drawing a comparison between women who consumed diet drinks less than once a week or not at all. The study was conducted on 81,714 post-menopausal women aged 50-79 years.

As per the findings of the study, women who drank two or more artificially sweetened beverages per day were 23 percent more likely to have a stroke, 31 percent more likely to have ischemic stroke, and 29 percent were at risk of developing heart disease (fatal or non-fatal heart attack). In addition, there was a 16 percent risk of deaths from any cause.

Apart from this, the risk of stroke doubled in women without previous heart disease or diabetes and obese women without previous heart disease or diabetes.

"Many well-meaning people, especially those who are overweight or obese, drink low-calorie sweetened drinks to cut calories in their diet. Our research and other observational studies have shown that artificially-sweetened beverages may not be harmless and high consumption is associated with a higher risk of stroke and heart disease," said lead author.

However, the results in post-menopausal women may not be generalisable to men or younger women.
"The American Heart Association suggests water as the best choice for a no-calorie beverage," suggested a researcher.
 
"Since long-term clinical trial data are not available on the effects of low-calorie sweetened drinks and cardiovascular health, given their lack of nutritional value, it may be prudent to limit their prolonged use," he added.

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This Could Impair The Immune System

Researchers have now discovered how the fungus -- Aspergillus fumigatus -- knocks out the immune defences, enabling a potentially fatal fungal infection to develop.

While, healthy people usually have no problem if microorganisms find their way into their bodies as their immune defence system will put the spores out of action, a specific type of fungus can threaten lives with a compromised immune system, such as AIDS patients or who are immunosuppressed following an organ transplantation, says a new study.

Researchers have now discovered how the fungus -- Aspergillus fumigatus -- knocks out the immune defences, enabling a potentially fatal fungal infection to develop.

Among other factors, it is gliotoxin -- a potent mycotoxin -- that is responsible for the pathogenicity of Aspergillus fumigatus.

Pathogenicity refers to the ability of an organism to cause disease.

"It was known that this substance has an immunosuppressive effect, which means that it weakens the activity of cells of the immune defence system. However, it had not been clear previously how exactly this happens," said a Professor.

To achieve this, they brought immune cells into contact with synthetically produced gliotoxin. These cells -- neutrophilic granulocytes -- represent the first line of the immune defence system.

Their task is to detect pathogens and eliminate them. As soon as such a cell comes into contact with a pathogen, for example a fungus, it releases specific messenger substances (leukotrienes) into the blood, which attract other immune cells. Once a sufficiently large number of immune cells has gathered, they can render the intruder harmless, findings showed.

This does not happen if the pathogen Aspergillus fumigatus is involved. Gliotoxin ensures that production of the messenger substance leukotrieneB4 in the neutrophilic granulocytes is inhibited, so that they are unable to send a signal to other immune cells. This is caused by a specific enzyme (LTA4 hydrolase) being switched off by the mycotoxin.

"This interrupts communication between the immune cells and destroys the defence mechanism. As a result, it is easy for spores - in this case the fungus - that enter the organism to infiltrate tissues or organs," said the Prof.
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This novel method can predict fatal heart disease

A novel method called stress cardiac MRI can not only diagnose heart disease, but can also predict which cases are potentially fatal, suggests a new research.

The study showed that predicting mortality is a key requirement for the technology to be more widely used. 

In addition, results suggest cardiac magnetic resonance (CMR) has the potential to be a non-invasive, non-toxic alternative to stress echocardiograms, catheterisations and stress nuclear exams in identifying the severity of the coronary heart disease.

"We've known for some time that CMR is effective at diagnosing coronary artery disease, but it's still not commonly used and represents less than one per cent of stress tests used in this country," said  senior author of the study.

For the study, researchers analysed data from more than 9,000 patients who underwent CMR.

The findings, showed that for patients without any history of  heart disease and at low-risk based on traditional clinical criteria, those with an abnormal CMR scan were 3.4 times more likely to die compared to patients with a normal CMR scan.

For the entire patient population, there was a strong association between an abnormal stress CMR and mortality, even after adjusting for patient age, sex and cardiac risk factors, the team found.

While non-invasive cardiac stress testing is a cornerstone in the clinical management of patients with known or suspected coronary artery disease, CMR works as well or better than other exams at identifying heart wall motion, cell death and the presence of low blood flow, said the study.

Furthermore, the technology does not require any radiation exposure, which is essential in nuclear stress tests.

"With the findings from this study suggesting that stress CMR is effective in predicting mortality, we provide a strong basis for a head-to-head study between stress CMR and other modalities," the author noted.

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