If inflammation is involved in causing Parkinson’s disease, how exactly could that happen?

Dr. Osama Abu-hadid, a movement disorder specialist and assistant professor of neurology at the Parkinson’s Center at the Neuroscience Institute and the Department of Neurology at Hackensack University Medical Center and Hackensack Meridian School of Medicine, told MNT that there is currently no “hard” proof as to the exact mechanisms in which the immune system plays a role in the development of Parkinson’s disease.

“However, there are multiple theories along with associated studies that give some guidance,” he said. “One of the proposed mechanisms is impairment of the blood-brain barrierTrusted Source, allowing easier access of the immune system into the brain tissue, hence, exposing this system to native antigens it has not seen before.”

“Examples of such antigens include abnormal alpha-synuclein aggregatesTrusted Source [and] the debris of dopaminergic neuronsTrusted Source that underwent cell death due to energy failure or abnormal accumulation of non-functional proteins due to impaired cellular recycling pathways,” Dr. Abu-hadid added. “This exposure may agitate the immune system, both innate and adaptive, adding ‘fuel to the fire’.”

Dr. Alessandro Sette, professor at the Center for Autoimmunity and Inflammation and Center for Infectious Disease and Vaccine Research at La Jolla Institute, said his study from April 2020, published in Nature CommunicationsTrusted Source, provides evidencethat the effect of the immune system on a certain part of the brain called the substantial nigraTrusted Source also plays a role in Parkinson’s disease development.

“When the substantia nigra is lost beyond a critical threshold and little of it remains, the clinical signs of cognitive loss and movement disorders become apparent, and the disease is diagnosed,” he explained. “But why is the substantia nigra lost?”

“Here the idea is that the immune system is involved, with a misplaced attack on the substantia nigra,” Dr. Sette continued. “Essentially the immune system mistakenly believes that the substantia nigra is foreign or dangerous and attacks it in a process called auto-immunity.”

And Dr. Tan Eng King, deputy chief executive officer of academic affairs and senior consultant in the Department of Neurology for the National Neuroscience Institute and one of the authors of a studyTrusted Source on Parkison’s disease and the immune system, said that determining the exact cause-and-effect relationship between neuroinflammation and neurodegeneration in Parkinson’s disease is challenging as the effect likely occurs cumulatively years before neuronal loss and clinical manifestations.

“Several clinical studies using blood and cerebrospinal fluidTrusted Source in Parkinson’s disease patients showed immune cell problems supported by evidence of changes in pro-inflammatory and anti-inflammatory markers in patients compared to healthy individuals,” he explained to MNT.

“There is also a suggestion that gut bacteria in Parkinson’s diseaseTrusted Source are different from healthy people and their metabolites are linked to inflammatory processes that may promote neurodegeneration,” Dr. King added.

As further research unveils more about the link between the immune system and Parkinson’s disease, experts agree it may open doors for the development of new therapies or even protection against developing the disease.

“Understanding how the immune system may be a player in the neurodegeneration seen in the brains of people with Parkinson’s disease opens up a whole array of potential treatment options,” commented Dr. Rebecca Gilbert, vice-president and chief scientific officer for the American Parkinson Disease Association (APDA).

“Maybe we don’t have to stop the alpha-synuclein from accumulating if we can stop the immune response that is triggered [by] the accumulation,” she hypothesized.

“There are drugs already in clinical use that control the immune response,” Dr. Gilbert continued.

“It is possible that using existing medications that decrease inflammation or developing new medications that decrease inflammation can be used as treatments for Parkinson’s disease. In fact, APDA is funding research in this area. For example, Dr. Martine Tetrault is studying fat metabolism in peripheral blood immune cells of people with Parkinson’s disease and healthy controls to see if a fat-altering drug can reduce the inflammatory signals in these cells.”

– Dr. Rebecca Gilbert

“In my opinion, the big reason it is exciting to think about Parkinson’s disease beginning outside the brain in the immune system is that we could potentially identify people who are at risk for Parkinson’s disease prior to them having the disease,” Dr. Pilitsis added.

“To accomplish this, we would need to understand which patients are at risk by studying their geneticsTrusted Source. Then we would need to watch for the early warning signs and start treatments either with existing anti-inflammatory medications or ideally with therapies that are personalized for the patient,” said Dr. Pilitsis.

Even though the exact cause of Parkinson’s remains unknown, there are various changes that people can make to their lifestyle that can help protect their immune system and potentially reduce the risk of Parkinson’s disease and similar conditions.

“It makes intuitive sense that instituting lifestyle modifications that potentially decrease inflammation may decrease [the] risk of Parkinson’s disease,” Dr. Gilbert said.

“Exercise, for example, has been shown to reduce inflammation and is probably one of the many reasons that exercise reducesTrusted Source the risk of Parkinson’s disease and also improvesTrusted Source symptoms of established Parkinson’s disease,” she noted.

Dr. Pilitsis agreed exercise has been shown to have a positive effect on outcomes for those with Parkinson’s disease.

“Also we should avoid things like excessive alcohol and nicotine that we know have negative effects on the immune system,” she added. “[And] managing our stress as best as possible can slow and help maximize outcomes of many diseases.”

When it comes to what we eat, Dr. Gilbert said there is evidence that the Mediterranean and the MIND diets are good for brain health.

“The MIND diet emphasizes whole grains, vegetables, nuts, legumes, and berriesTrusted Source,” she detailed. “Fish is the preferred protein and olive oil is the preferred fat. Recently a study was published that showedTrusted Source adherence to the MIND diet and the Mediterranean diets were associated with later onset of Parkinson’s disease.”