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Brain’s recycling system breaks down in Parkinson’s Disease

Brain’s recycling system breaks down in Parkinson’s Disease

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A recent study suggests that the usual house-cleaning activity of neuronal cells may fail in Parkinson’s disease. A buildup of damaged proteins in brain synapses, which may eventually result in patches of dead neurons, is one of the symptoms of Parkinson’s disease.

According to a study done on fruit flies called Drosophila, a calcium surge in healthy brain synapses starts the cleaning process by causing a protein that causes cells to throw away the waste. But, when a gene mutation known to cause Parkinson’s disease is present, the protein does not react to calcium’s signal as it should, and synaptic cleanup is not successful.

According to a recent study, the typical process for getting rid of broken-down proteins in brain cells is disrupted by a gene mutation linked to Parkinson’s disease. As a result, synapses may accumulate debris, which could lead to Parkinson’s symptoms.

Researchers used Drosophila, or fruit flies, to explore how calcium releases in neurons cause autophagy or cell cleaning, and how a gene mutation prevents this release.

In the synapses of persons with Parkinson’s disease, abnormal protein clumps called Lewy bodies are discovered. These Lewy bodies are mostly made up of clumps of the protein alpha-synuclein. Normally, alpha-synuclein participates in the communication between brain cells. Misfolded alpha-synuclein proteins, on the other hand, clump together and destroy neurons, leaving dead brain cells in their wake.

Dr. Warren D. Hirst of Biogen claims that the idea that Parkinson’s is brought on by a malfunction in autophagy is not new. The new study, however, meticulously outlines the potential culprits and underlying mechanisms of autophagy’s failure. (Dr. Hirst did not take part in the research.)

Parkinson’s disease

After Alzheimer’s disease, Parkinson’s disease is the neurodegenerative condition that is most frequently diagnosed. Parkinson’s disease affects almost one million Americans, and by 2030, that figure is projected to reach 1.2 million. Parkinson’s disease affects about 10 million individuals globally. In the United States, almost 90,000 new cases are diagnosed yearly.

Critical basal ganglia dopamine-producing neurons die in the disease’s advanced stages. This area of the brain regulates movement.

The primary signs of Parkinson’s disease are:

Parkinson’s disease may also result in skin concerns, bladder problems, constipation, trouble eating, chewing, and communicating, as well as sadness and other emotional disturbances.

The majority of Parkinson’s patients are over 60 years old, while 5% may be diagnosed earlier. The extent to which the condition may be inherited is unclear.

It’s crucial to remember that everyone is affected by the ailment differently; some people may have more severe symptoms, such as losing all mobility, while others may still just have mild symptoms. Although there is no known cure for Parkinson’s disease, there are treatment options that can help manage the symptoms, including drugs, deep brain stimulation (DBS), and treatments.

Parkinson’s disease may also result in skin concerns, bladder problems, constipation, trouble eating, chewing, and communicating, as well as sadness and other emotional disturbances. The majority of Parkinson’s patients are over 60 years old, while 5% may be diagnosed earlier. The extent to which the condition may be inherited is unclear.

It’s crucial to remember that everyone is affected by the ailment differently; some people may have more severe symptoms, such as losing all mobility, while others may still just have mild symptoms.

Although there is no known cure for Parkinson’s disease, there are treatment options that can help manage the symptoms, including drugs, deep brain stimulation (DBS), and treatments.

Calcium, autophagy, and Parkinson’s risk

It is “a basic mechanistic work taking a mutation that is known to raise the incidence of Parkinson’s, and investigating what that mutation does in a fruit-fly model of Drosophila,” according to neuroscientist Dr. Santosh Kesari, who was also not involved in the study.

The researchers discovered that the earliest indirect trigger of autophagy in Drosophila was an influx of calcium at brain synapses. Also, they found that these synaptic calcium surges can be brought on by either neuronal activity or by depriving cells of amino acids.

Associate Professor of Neurology Ian Martin, who was not involved in the study, stated, “The authors give considerable data suggesting a role for calcium in the onset of autophagy within Drosophila synapses.

According to Asst. Prof. Martin, “A variety of approaches, including biochemistry, genetics, synaptic physiology, and microscopy, are generally well-supportive in the study of the idea that synaptic autophagy could be coupled to neuronal activity, and that this autophagy is required for neuronal survival.” Autophagy, according to Dr. Kesari, “is the cell’s trash disposal.”

Parkinson’s disease and EndoA

The study then showed that a mutation in the Endophilin-A protein, also known as “EndoA,” which is linked to Parkinson’s disease, is responsible for the relationship between calcium and autophagy.

The endolysosomal system, which includes EndoA, has been linked in other research as a putative early pathomechanism causing Parkinson’s disease and alpha-synuclein aggregates.

Normally, the calcium influx increases EndoA’s flexibility, allowing for the creation of the autophagosomes that power autophagy. However, the study discovered that in those who have the Parkinson’s-related mutation, the calcium influx makes EndoA stiffen, and this stiffness prevents the creation of autophagosomes, which in turn prevents autophagy.

So, the new work is distinctive in two ways: it focuses on autophagy particularly at synaptic terminals and shows how the Parkinson’s disease-related gene mutation prevents the process from starting.

Making use of the study’s insights

According to studies from human post-mortem tissue, Asst. Prof. Martin said that the idea that autophagy failure plays a role in Parkinson’s is validated. Beside EndoA, Parkinson’s disease is also thought to be caused by pathogenic mutations in proteins including alpha-synuclein and LRRK2.

Autophagy abnormalities are frequently implicated in Parkinson’s disease-related neurodegeneration, according to genetic studies.

In conclusion, Dr. Kesari remarked, “We need to think about how we can use this information to improve autophagy.” The next phase of the research with human cells is still to be completed.

A crucial, $64,000 question, according to Dr. Hirst, is how to accomplish this. The field is still looking for agents that boost autophagy. This still presents difficulties.

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Can you workout while doing an intermittent fast?

Can you workout while doing an intermittent fast?

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A diet plan known as intermittent fasting alternates between eating and not eating. Intermittent fasting cycles can occur hourly or daily. Individuals could decide to fast for religious, dietary, or health-related reasons.

People may want to start or continue exercising while on an intermittent fast (IF). Fasting and exercise are both possible, but care must be taken.

Exercise while fasting

Fasting individuals are permitted to exercise. Some people work out during IF because they think it might be good for their health. They consist of:

Loss of weight

When humans ingest carbs, their bodies transform them into glucose, a sort of sugar. Glycogen is how the body stores glucose.

Study indicates that glycogen levels are depleted during fasting intervals. Hence, the body begins to burn fat to a reliable Supply of energy for physical activity that may aid in weight loss.

According to one study, exercising when fasted resulted in greater fat reduction than exercising after eating. Nonetheless, different findings from other studies have been obtained.

According to a 2014 study, exercising the next day after an overnight fast did not result in greater weight loss than exercising the day before a meal. Another mouse study came to the conclusion that IF, with or without exercise, caused mice to lose weight effectively.

In order to lose weight, a person’s daily caloric intake must be lower than their daily caloric expenditure. IF may aid in weight loss because it restricts the caloric intake of the participant. In a study comparing intermittent fasting (IF) to a calorie-restricted diet without fasting intervals, the amount of weight lost by each group was similar.

Autophagy

A review of studies examining the effects of exercise and fasting reveals that it might boost autophagy.

Autophagy is a process that aids in the elimination of undesirable or damaged cells in order to regenerate new, healthier ones.

Anti-aging

Diet and exercise may slow down the ageing and disease processes, according to a 2018 study. This is due to the possibility that IF and exercise could alter metabolism.

Why it might not be effective?

Exercise while fasting may have some unfavourable side effects, according to research. They may consist of

  • Poorer performance: According to research, IF may reduce exercise performance, especially in highly trained athletes.
  • Difficulty to gain muscle: A 2018 randomised controlled experiment indicated that males who were on the intermittent fasting protocol gained less muscle than those who ate their regular meals. Yet, IF had no detrimental effects on their ability to retain muscle. This is corroborated by another study, which shows that IF may help retain muscle mass.
  • Headache: IF and exercise, both can reduce blood pressure. When the two are combined, a person could become dizzy as a result of their blood pressure dropping.
  • Blood sugar: Exercise and IF both have the potential to lower blood sugar levels. A person may faint if their sugar levels drop too low.

Fasting and exercise-related studies appears to include contradictory findings. A person may wish to attempt IF for fat loss depending on their fitness objectives. Nonetheless, various diets might be used if someone wishes to gain muscle.

Types of intermittent fasting

Intermittent fasting comes in many different forms. They consist of:

  • 16:8: During a 16:8 fast, one will go without food for 16 hours before having an 8-hour window during which they can eat. People are permitted to drink non-calorie beverages including water, black coffee, and black tea throughout the 16 hours of fasting.
  • 5:2: The 5:2 diet is eating regularly on five days and fasting for two of those days.
  • Daily: A daily fast entails going without eating for an extended period of time, usually from the evening to the morning after. An extended fast of 13 hours during the course of the night, according to a 2016 study, may lower women’s chance of developing breast cancer.
  • Up to the ninth hour: During this fast, the first eight hours of the person’s awake day are spent without eating. The person can then start eating at the ninth hour.
  • One meal a day (OMAD) fasting entails choosing one meal to consume each day and fasting the rest of the time.
  • Alternate Day: As the name implies, alternate day fasting involves eating normally one day and going without meals the next.

It is important to speak with a doctor or dietitian before changing one’s normal eating habits, especially if the adjustment involves fasting.

Planning the workout

To keep safe during IF, it’s crucial to schedule workouts. A few things to think about are:

Exercise type: There are two different forms of exercise, anaerobic and aerobic. Running, walking, and cycling are examples of continuous aerobic exercise, also known as “cardio.” Anaerobic exercise, like weightlifting or running, calls for all-out effort in a brief period of time.

The kind of fast a person keeps will probably influence the type of exercise they perform. For instance, someone who observes the 16:8 or overnight fasts can exercise both aerobically and anaerobically while they are eating.

On the other hand, if someone is following the alternate day regimen and wants to exercise on their non-eating day, they should definitely stick to less strenuous cardiovascular activity.

Exercise timing: Although a person can exercise while fasting, it may be preferable to time exercise for just after meals.

Food type: It’s crucial to think about what to eat if you plan to exercise while eating.

Instead of just before activity, pre-workout nutrition should include a meal eaten two to three hours beforehand. It might also be high in protein and complex carbohydrates, like whole grain cereal.

To aid in recuperation, a post-workout meal should include carbohydrates, high-quality proteins, and fats.

Safety tips

During workout preparation, it is important to think about the following safety advice.

  • Exercise immediately following meals will give one the energy they need to finish an exercise.
  • Keeping it low-intensity: If a person is fasting, they may want to try low-intensity aerobic exercise. However, it is typically okay to engage in any form of exercise after eating.
  • Paying attention to what the body is telling you: If someone is on IF and beginning to feel sick while exercise, they should stop.
  • Water intake: Even when not IF, it’s crucial to drink water throughout activity. As water makes up the majority of the human body, it is crucial to replenish fluids lost during exercise.

Exercise and fasting may be particularly hazardous for some persons, including:

  • those who have diabetes
  • low blood pressure sufferers
  • individuals with a history of disordered eating
  • expecting mothers
  • mothers who are nursing

It is best to talk to your doctor about trying IF and exercising if you have underlying medical concerns.

REFERENCES:

  • https://www.medicalnewstoday.com/articles/intermittent-fasting-and-working-out
  • https://www.healthline.com/health/food-nutrition/intermittent-fasting-tips
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021351/
  • https://www.wikihow.health/Exercise-While-Intermittent-Fasting

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