Health

Parkinson’s Disease: New Information on the Malfunctioning of the Brain’s Recycling System

  • 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 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.
  • 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 unsuccessful.
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-synucleinTrusted Source. Normally, alpha-synuclein participates in the communication between brain cells. Alpha-synuclein proteins that are misfolded, 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 was not a part of the investigation.
 

Things To know About Parkinson’s Disease

Things to know about 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:

  • a shaking sensation in the hands, head, arms, jaw, or legs
  • slow movement
  • muscular contractions that are rigid and last a long time
  • reduced balance and coordination, with a risk of falling

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.

A healthy diet and regular exercise may help prevent and treat the condition as well as other neurological disorders like Alzheimer’s, according to a growing body of existing research. According to a recent study, just 6 minutes of intense exercise might increase the body’s levels of the neuroprotective brain-derived neurotrophic factor (BDNF), which may help postpone the onset of Parkinson’s and Alzheimer’s illnesses.

 

Parkinson’s Risk, Autophagy, and Calcium

Dr. Santosh Kesari, a neuroscientist who was not involved in the work, described it as a straightforward mechanistic paper that examined the effects of a mutation known to raise the risk of Parkinson’s disease in a fruit-fly model of the Drosophila.
 
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.
 
According to Ian Martin, an associate professor of neurology who was not involved in the work, the authors present strong evidence in favor of a function for calcium in the start of autophagy within Drosophila synapses.
 
Specifically, Assistant Professor Martin noted An assortment of methods used in the study, including biochemistry, genetics, synaptic physiology, and microscopy, provide generally strong support for the hypothesis that synaptic autophagy may be related to neuronal activity and that this autophagy is necessary for neuronal survival. Autophagy, according to Dr. Kesari, is the cell’s method of disposing of waste.
 

EndoA and Parkinson’s Disease

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.
 
EndoA is a component of the endolysosomal system, which earlier research has suggested may be an early pathomechanism for Parkinson’s disease and alpha-synuclein clumps.
 
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 with 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 Parkinson’s disease-related gene mutation prevents the process from starting. These revelations add to our understanding of how the disease functions.
 

Utilizing The Study’s Findings

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 like alpha-synuclein and LRRK2Trusted Source.
 
Autophagy abnormalities are repeatedly implicated in Parkinson’s disease-related neurodegeneration, according to genetic studies. Dr. Kesari explained that we still have more work to perform in human cells before considering how we may apply this knowledge to enhance autophagy.
 
The crucial, $64,000 question, according to Dr. Hirst, is how to accomplish this. The field is still looking for agents that boost autophagy. This keeps being difficult. According to assistant professor Martin, the EndoA mutation is not a good therapeutic target and it is unclear how treatments might attempt to restore the lost function brought on by the mutation.
 

Conclusion

A recent study has identified how a gene mutation linked to Parkinson’s disease can disrupt the typical process of getting rid of broken-down proteins in brain cells. Researchers used fruit flies to explore how calcium releases in neurons cause autophagy or cell cleaning, and how a gene mutation prevents this release. Autophagy is the cell’s method of disposing of waste, and when a gene mutation related to Parkinson’s disease is present, the cleaning process by neuronal cells can fail. As a result, synapses may accumulate debris, which could lead to Parkinson’s symptoms. 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.

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