Molecular Mechanisms of Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disease that affects dopaminergic (dopamine-producing) neurons (nerve cells) in the area of the brain called the substantia nigra. The cause of PD is currently unknown. One area of ongoing PD research is to identify the molecular mechanisms of PD to help diagnose PD sooner and provide paths to a new treatment. Earlier PD diagnosis will allow for earlier treatment to slow the disease progression.

Key takeaways:
  • arrow-right
    Parkinson’s disease (PD) is a neurodegenerative disease that affects dopaminergic (dopamine-producing) neurons (nerve cells) in the area of the brain called the substantia nigra.
  • arrow-right
    The authors of a new study solved the mystery of how the abnormal aggregates of α-synuclein continue to spread and destroy neurons in the brain, which ultimately leads to the symptoms of PD.
  • arrow-right
    Approximately 60,000 Americans are diagnosed with PD each year and it is expected that there will be 1.2 million people with PD by 2030.
  • arrow-right
    Complications of PD are the 14th leading cause of death in the U.S.
  • arrow-right
    Research into the molecular mechanisms of PD holds promise for new, more effective medication and identifiable biomarkers that may help to diagnose PD sooner.

What is known about Parkinson’s disease?

PD is a neurodegenerative disease affecting dopaminergic neurons (dopamine-producing nerve cells) in the brain. Approximately 60,000 Americans are diagnosed with PD each year and it is expected that there will be 1.2 million people with PD by 2030. PD is not terminal, however, complications of PD, such as dementia, are the 14th leading cause of death in the U.S.

There are motor symptoms (movement) and non-motor symptoms that result from PD.

Motor symptoms include tremors, muscle stiffness (rigidity), problems with balance, slowness of movement (bradykinesia), and small amounts of movement (hypokinesia).

Non-motor symptoms can be the most life-altering for PD sufferers and include depression, anxiety, hallucinations, constipation, and sleep disorders.

Treatment for PD includes medication, lifestyle modifications, and surgery.

There is no cure yet for PD, however, treatment may slow disease progression. It is imperative to be under the care of a neurologist (physician specializing in diseases of the brain, spinal cord, nerves, and muscles). Following the treatment plan developed by a neurologist can help people with PD have a great quality of life.

Recent research into the molecular mechanisms of PD holds promise for new, more effective medication and identifiable biomarkers that may help to diagnose PD sooner.

One study may resolve a Parkinson’s mystery

A study published August 22, 2022, in Nature Communications, according to MedicalXpress, “could resolve one of the mysteries of Parkinson's disease and lead to new strategies for treating or preventing the neurological disorder."

What was already known about PD

Research over the past several years has shown that neuron (nerve cell) death in the brain of people with PD follows the spread of abnormal groupings (aggregates) of a brain protein, called alpha-synuclein (α-synuclein).

These abnormal aggregates of α-synuclein start out inside the nerve cell. The abnormal aggregates then trigger normal α-synuclein to also become abnormal and begin to group up. This is how the α-synuclein spreads in the brain of a person with PD. The aggregates of α-synuclein then cause the death of the nerve cells in the brain. This process causes the person with PD to have the symptoms of PD. Once it begins, this process happens over decades and causes the PD symptoms to worsen over time.

What previously was not fully understood is how the groupings of protein spread to other neurons.

The discovery

Lysosomes are the part of every cell that digests or recycles cell waste so it can then be reused by cells. Normally lysosomes essentially digest and recycle cell waste, then return the cleaned material to the original cell to be reused.

The results of this study show that abnormal α-synuclein originates inside the nerve cell and spreads via an impaired “cellular waste-ejection process.”

The abnormal α-synuclein accumulates in the “capsule-like waste bins in cells called lysosomes” and instead of getting digested or recycled by the lysosomes, the α-synuclein aggregates remain largely intact – they do not get broken down or encapsulated by the lysosome.

The lysosome then releases the aggregates (lysosomal exocytosis process) whole and unencapsulated back into the neurons, where they continue to spread. This impaired lysosomal exocytosis process is as if a person puts a contaminated bottle into the recycle bin and then the contaminated bottle is returned for reuse without being decontaminated or recycled.

This discovery solved the mystery of how the abnormal aggregates of α-synuclein continue to spread and destroy neurons in the brain, which ultimately leads to the symptoms of PD.

While more research is needed to confirm and expand this PD molecular mechanism discovery, anticipation for future application is high.

New treatment on the horizon?

Further experiments by the study authors showed that when lysosome exocytosis was slowed, the concentration of the abnormal aggregates was reduced. It is possible to decrease the amount of abnormal α-synuclein circulating inside the brain’s nerve cells.

Study author Dr. Manu Sharma said in a MedicalXpress article that this discovery could suggest a future approach to treating Parkinson's. "We don't know yet, but neurons might be better off, even in the long term, if they keep these aggregates inside their lysosomes," he said. When the aggregates stay inside the lysosome, they are walled off from replicating. It is believed this would slow PD progression.

Because of PD research, new treatment options in the future are likely.

What does ongoing research mean for people with PD?

Ongoing research is bringing scientists from different disciplines together. Breakthroughs are happening that bring hope to people with PD. According to the Parkinson’s Foundation, “Scientists are exploring ways to identify biomarkers for PD that can lead to earlier diagnosis and more tailored treatments to slow down the disease process.”

While there is no cure yet for PD, it is reasonable, based on research breakthroughs, to expect a future with earlier diagnosis and new treatment options.

Resources:

Leave a comment

Your email address will not be published. Required fields are marked