Parkinson’s disease is one of the most common brain disorders in the world. It mainly affects older adults, although some people develop it at a younger age.
Nearly one million people in the United States are living with Parkinson’s disease, and millions more are affected worldwide.
The disease slowly damages brain cells that control movement. At first, a person may notice a slight tremor in one hand, stiff muscles, or slower movements. As time passes, walking, balancing, writing, speaking, and other everyday tasks can become much more difficult.
Many people do not realize that Parkinson’s disease can also affect thinking and memory. As the illness progresses, some people develop dementia, making it harder to remember information, make decisions, or carry out daily activities.
A closely related condition called Lewy Body Dementia, or LBD, often causes memory and thinking problems much earlier in the disease. Around 1.4 million Americans are living with LBD, making it one of the most common forms of dementia.
Scientists have been trying for many years to understand why these diseases begin and why they spread through the brain. A new study from researchers at Scripps Research has uncovered an important clue that could one day lead to better treatments. The findings were published in The Journal of Neuroscience.
The research focused on a protein called alpha-synuclein. Proteins are important building blocks that help cells perform many different jobs. Normally, alpha-synuclein has useful roles inside nerve cells.
However, in Parkinson’s disease and Lewy Body Dementia, this protein changes shape and sticks together, forming harmful clumps. These clumps damage brain cells and are considered one of the main features of both diseases.
Healthy cells have their own waste disposal and recycling system, called autophagy. This system constantly removes damaged proteins and other unwanted material before they can cause harm. You can think of autophagy as the cell’s cleaning crew. When it works well, it keeps the inside of the cell clean and healthy.
The researchers discovered that this cleaning system does not work properly in Parkinson’s disease and LBD. One reason appears to be the buildup of highly reactive nitrogen-containing molecules, especially nitric oxide. Although nitric oxide has many normal jobs in the body, too much of it can damage important proteins inside cells.
One of the proteins affected is called p62. Under normal conditions, p62 helps collect unwanted material, including alpha-synuclein, and sends it to the cell’s recycling system for disposal. In the new study, the scientists found that nitric oxide changes p62 through a chemical process known as S-nitrosylation. This change prevents p62 from doing its job properly.
When p62 no longer works as it should, the cell cannot clear away alpha-synuclein efficiently. Harmful protein clumps begin to grow inside brain cells. Even more concerning, these clumps can move from one brain cell to another.
This creates a chain reaction, allowing damage to spread through different parts of the brain over time. Scientists believe this spreading process helps explain why symptoms gradually become worse.
The discovery offers a promising new target for future treatments. If researchers can develop medicines that prevent p62 from being damaged by S-nitrosylation, the cell’s natural recycling system may continue working normally. This could help remove alpha-synuclein before large clumps form and reduce the spread of damage through the brain.
The findings also support growing evidence that oxidative stress, which happens when harmful reactive molecules build up faster than the body can control them, plays an important role in many brain diseases.
Researchers are continuing to investigate whether healthy lifestyle habits and nutrients such as vitamins E and D may help protect brain cells, although much more research is needed before these approaches can be recommended as treatments.
The study was led by Dr. Stuart Lipton and colleagues at Scripps Research and published in The Journal of Neuroscience. Although this research is still at an early stage and has not yet produced a new treatment, it provides valuable insight into how Parkinson’s disease and Lewy Body Dementia develop.
By understanding exactly why the brain’s natural cleaning system fails, scientists hope to design future therapies that slow or even stop these devastating diseases before they cause widespread damage.
If you care about Parkinson’s disease, please read studies that Vitamin B may slow down cognitive decline, and Mediterranean diet could help lower risk of Parkinson’s.
For more information about brain health, please see recent studies that blueberry supplements may prevent cognitive decline, and results showing Plant-based diets could protect cognitive health from air pollution.
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