Sep
09
2023

How the Immune System affects Parkinson’s Disease

By | autoimmune disease, diet, Fitness, immune system, Inflammation, Parkinson’s disease

This article explains how the immune system affects Parkinson’s disease (PD). Notably, in the past physicians thought that Parkinson’s disease was due to a degenerative change of the substantia nigra. This explained why balancing was a problem, why shaking of the hands occurred and why falls happened often. It it important to realize that nobody thought about the immune system.  And no-one knew that an autoimmune process could be behind Parkinson’s disease.

T cells that react to a damaged protein called alpha-synuclein

There are specific changes in the immune system approximately 10 years before Parkinson’s disease symptoms occur in patients who come down with the disease. Researchers from the La Jolla Institute for Immunology showed that T cells play a key role in causing PD. They react to a damaged protein called alpha-synuclein build up in the dopamine-producing brain cells. Laboratory physicians can assay this through a simple blood test, which becomes a screening tool for early Parkinson’s disease. The reactive T cells stay around for about 10 years, then fade away. There seem to be other immune factors that weaken the initial aggressive phase of the T cells.

The role of inflammation in Parkinson’s

When the immune system malfunctions chronic inflammation can develop. In farmers exposed to pesticides the later development of Parkinson’s disease was observed. The researchers thought that the pesticides caused an irritation of the immune system leading to chronic inflammation. There is evidence that the gut bacteria are different in Parkinson’s disease patients when compared to normal controls. The gut absorbs the metabolites of the abnormal gut bacteria and causes chronic inflammation. In an attempt to stop the inflammatory process, the immune system can develop autoimmune antibodies, which can cross react with cells of the substantia nigra. This in turn can cause Parkinson’s disease.

Lifestyle factors that people can change to prevent PD

Dr. Rebecca Gilbert, vice-president and chief scientific officer for the American Parkinson Disease Association (APDA) commented on the importance of lifestyle changes. She said: “It makes intuitive sense that instituting lifestyle modifications that potentially decrease inflammation may decrease the risk of Parkinson’s disease. Exercise, for example, has been shown to reduce inflammation and is probably one of the many reasons that exercise reduces the risk of Parkinson’s disease and also improves established Parkinson’s disease.” She commented further: “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.”

Changing diet can help postpone Parkinson’s disease

With regard to the best diet that will help Parkinson’s disease patients she said: “The MIND diet emphasizes whole grains, vegetables, nuts, legumes, and berries. Fish is the preferred protein and olive oil is the preferred fat. Recently a study showed that adherence to the MIND diet and the Mediterranean diet had an association with later onset of Parkinson’s disease.”

The gut connection to Parkinson’s disease

According to the WHO the global prevalence of Parkinson’s disease has doubled in the last 25 years. At this point we do not know why this is so. But many investigations have shown that there is a significant difference in the gut bacteria composition of healthy controls and Parkinson’s disease patients. There is a 30% difference between the bacterial composition of healthy controls and patients with Parkinson’s disease. This has led to Braak’s Hypothesis of Parkinson’s Disease. This hypothesis says that an unknown pathogen enters through the nose, the person swallows it and it ends up in the gut. Absorption gets it into the gut wall and it migrates through the vagus nerve into the central nervous system where it leads to accumulation off alpha-synuclein in the substantia nigra. This destroys the dopamine producing cells in that region causing the symptoms of PD.

Can any diet fight gut dysbiosis?

  • In 2022 study they found that flavonoids, the pigments of fruit were associated with a lower mortality of patients with Parkinson’s disease.
  • In an earlier study of 2018 researchers determined that a protein from fish with the name parvalbumin helped Parkinson’s patients to stop producing alpha-synuclein. PD patients suffer from clumping of alpha-synuclein, which causes their symptoms.
  • Restriction of refined carbohydrates “especially diets with a low glycemic index, rich of vitamins and polyphenols, a Mediterranean diet for example, can be recommended”.

Regular exercise to prevent Parkinson’s disease

Regular physical exercise maintains body function and muscle strength. Dr. Emer MacSweeney said: “Being physically active is one of the best things you can do for your body. Exercise helps protect against many diseases and keeps the heart, muscles, bones, and brain in optimum condition. Exercise promotes the oxygenation of the brain and stimulation of multiple neurochemicals.”

Several studies showed that patients with PD deteriorate slower, if they exercise regularly. Part of that response is due to the release of endorphins and serotonin, but we do not know all of the positive mechanisms of exercise at this time.

How the Immune System affects Parkinson’s Disease

How the Immune System affects Parkinson’s Disease

Conclusion

Recent research changed what we know about Parkinson’s disease (PD). Braak’s Hypothesis of Parkinson’s Disease states that an unknown pathogen enters through the nose, gets swallowed and ends up in the gut. From there it gets taken up into the gut wall and migrates through the vagus nerve into the central nervous system. There it leads to accumulation of alpha-synuclein in the substantia nigra. This destroys the dopamine producing cells in that region causing the symptoms of PD. But we also know that chronic inflammation can aggravate the symptoms of PD patients. When the composition of the gut bacteria deteriorates, this too will make PD patients worse.

Lifestyle changes help to postpone Parkinson’s disease

A healthy diet, like the MIND diet, DASH diet or the Mediterranean diet have beneficial effects on PD patients. Many studies also found that regular physical exercise is a stabilizing factor in PD patients. There are still many gaps in what we know about the causation of PD. But the above summarized factors are a good start.

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Aug
24
2019

Connection Between Parkinson’s Disease And The Removal Of The Appendix

By | Parkinson’s disease

In the first place, a large study from Cleveland Medical Center found a connection between Parkinson’s disease and the removal of the appendix. It is important to realize that Dr. Mohammed Z. Sheriff who was the main investigator assembled 62.2 million patients’ records. Of these 488,190 (0.78%) patients had an appendectomy done. 4,470 (0.92%) among these patients went on with a diagnosis of Parkinson’s disease. Of the remaining 61.7 million patients physicians eventually diagnosed 177,230 individuals (0.29%) with Parkinson’s disease. This means that the patients with a prior appendectomy had a 3.17-fold higher risk to develop Parkinson’s disease. Whoever did not have their appendix removed had a lower risk to develop Parkinson’s disease.

Older, smaller studies in the past were ambiguous

A 2016 Movements Disorders study with 1.5 million people in Denmark found that patients who had an appendectomy were a slightly higher risk of developing Parkinson’s disease later in life.

In contrast, a 2018 Science Translational Medicine study found the opposite among 1.6 million Swedes. Patients who had an appendectomy had a lower risk of developing Parkinson’s disease and there was a delay in the onset of it.

It was this discrepancy what motivated Dr. Mohammed Z. Sheriff to design the much larger study that he carried out. He presented the findings at the 2019 Digestive Disease Week meeting that took place May 18–21 in San Diego, CA.

Alpha-synuclein associated with Parkinson’s disease

At the same time other investigators found that alpha-synuclein, an abnormal protein in nerve cells, is important for the development of Parkinson’s disease. It plays a role in patients with appendicitis who need surgery. But it also is present in the substantia nigra in the brain of patients with Parkinson’s disease. Notably, patients with Parkinson’s disease often have problems with their balance, muscle rigidly, tremor and slowness of movements.

Indeed, alpha-synuclein has become an important marker for the development of Parkinson’s disease. This publication indicates that monocytes that are activated by the presence of alpha-synuclein can cause significantly more inflammation in the nerve cells of the substantia nigra in the brain. Other authors postulate that oxidative stress in vagal neurons may lead to alpha-synuclein, which can be transported from foci such as in the appendix to the substantia nigra in the brain. More recent studies have shown alpha-synuclein in the gut of patients with Parkinson’ disease according to Dr. Sheriff. In particular, it clearly shows that our gut biome plays a role in the development of disease.

Older people affected by Parkinson’s disease

Certainly, it is mostly people above the age of 60 that come down with Parkinson’s disease. Another key point is that there is no known effective treatment for Parkinson’s disease. However, the new information that alpha-synuclein is a factor in the early stages of Parkinson’s disease is most compelling evidence. By and large, this process leads to toxic clumps of Lewy bodies in nerve cells of the brain and in the gut wall including the appendix. Nobody knows exactly the meaning of Lewy bodies and alpha-synuclein. But if they are playing a part in the initiation of Parkinson’s disease, medications that fight oxidative stress in the nervous system may be a new approach to treating Parkinson’s disease. There is a need for more research.

New approaches to treat Parkinson’s disease

Here is a publication that points out that existing treatment for Parkinson’s disease does not include targeting alpha-synuclein. In the future, these authors state, this will change, as immunotherapy directed at alpha-synuclein will interrupt the development of Parkinson’s disease. Here is another publication that stresses the importance of alpha-synuclein in the development of Parkinson’s disease. It points to testing new therapies in animal experiments and in clinical trials.

Connection Between Parkinson’s Disease And The Removal Of The Appendix

Connection Between Parkinson’s Disease And The Removal Of The Appendix

Conclusion

The observation that people who had an appendectomy have a 3.17-fold higher risk to develop Parkinson’s disease led to more investigations. It became obvious that an alpha-synuclein accumulation in the nerve cells of the gut wall was playing a role in the disease and formed Lewy bodies. It confirms the concept that disease processes can start with our gut biome. These cells can travel via the vagal nerve into the part of the central nervous system, called substantia nigra. It is there that the dopamine producing nerve cells reside. Destruction of these dopaminergic nerve cells leads to the symptoms of Parkinson’s disease. One of the new approaches to treat Parkinson’s disease is by immunotherapy where antibodies destroy the alpha-synuclein protein. However, clinical trials will have to follow that are testing this new treatment possibility.

Sep
30
2017

Parkinson’s Disease May Be Stopped

By | coffee, depression, Diabetes, Drugs, Parkinson’s disease

Parkinson’s disease is common in the US; new research shows that the use of an old anti-depression medication can stopParkinson’s disease The use of nortriptyline, a 50-year old antidepressant has shown to normalize a nerve cell protein. In rats nortriptyline dissolved toxic alpha-synuclein clusters in brain cells. These toxic protein clusters seem to be happening in the brain of Parkinson’s disease patients also. It is the protein by the name of alpha-synuclein that research first found in rats to cause the toxic protein clusters in nerve cells of the substantia nigra, a part of the brain stem.

But nortriptyline was able to normalize the concentration of the protein. In preliminary studies in humans the investigators found that there was a significant improvement of Parkinson’s disease with the use of nortriptyline.

Placebo controlled trial with nortriptyline

Now a research team from Michigan State University in Grand Rapids conducted a larger clinical placebo-controlled trial. The lead researcher Collier of the study group found that Parkinson’s patients who received treatment for depression with the tricyclic agent nortriptyline needed less dopamine, the main drug used to treat Parkinson’s disease. This indicated to the researchers that nortriptyline was preserving brain cells that were still making their own dopamine. In rat experiments they could show that it was the dissolving of toxic alpha-synuclein proteins by nortriptyline that was the key to therapeutic success.

Lisa Lapidus, a co-worker on the Michigan State University research team summed up their research: “What we’ve essentially shown is that we are dealing with a drug that the FDA approved already 50 years ago. Patients tolerate the medication relatively well. This could be a much simpler approach to treating the disease itself, not just the symptoms.”

Parkinson’s disease may be stopped also by old diabetes drug

Thomas Foltynie found that the diabetes drug exenatide helps patients with Parkinson’s disease. Dr. Foltynie is a professor of neurology at the University College London and co-author of the study.

Exenatide is an injection drug. When preliminary studies showed that this drug was effective in helping Parkinson’s disease patients lose their problems with walking and balance, a formal study followed.

Professor Foltynie designed a study where 60 people with Parkinson’s disease either got injections of exenatide or placebo injections. Patient exams followed regarding their musculoskeletal system and balance at baseline and every 12 weeks. A score system of 132 points assessed their Parkinson’s disease. After 48 weeks those who had been taking exenatide had a gain of 1 point on that scale while the placebo group dropped 3 points. After 48 weeks the drug administration (exenatide) finished. But after another 12 weeks another scoring and assessment of the Parkinson’s disease symptoms took place. The experimental group on exenatide scored 3.5 points higher than the placebo group. This suggests that exenatide is helping to treat the cause of Parkinson’s disease, not just the symptoms.

Parkinson’s disease may also stop through the use of caffeine

Parkinson’s disease was in the news again because of another study that involved breaking up misfolded alpha-synuclein through caffeine.

Misfolded alpha synuclein forms clumps inside dopamine producing cells in the substantia nigra of the brain stem. Misfolded alpha synuclein acts like a toxin to the dopamine producing cells and eventually these cells die off. This is the brain region that is responsible for making muscle movements smooth and stabilizes balance. The cells that have misfolded alpha synuclein clumps in them also go under the name of “Lewy bodies”.

Dr. Jeremy Lee from the University of Saskatchewan (Saskatoon, Saskatchewan, Canada) has isolated two compounds from coffee. They are called C8-6-I and C8-6-N. They can bind to alpha-synuclein and prevent clumping, which stops the toxic effects on dopamine producing nerve cells. Like with nortriptyline the caffeine effect is a curative approach to Parkinson’s disease.

 

Parkinson’s Disease May Be Stopped

Parkinson’s Disease May Be Stopped

Conclusion

There is a new therapeutic approach to Parkinson’s disease. Researchers have detected a protein called alpha-synuclein to cause toxic protein clusters in nerve cells of the substantia nigra, a part of the brain stem. When these cells die from the accumulation of these misfolded proteins, patients come down with Parkinson’s disease. But three different methods of treatment can improve Parkinson’s disease by dissolving the protein alpha-synuclein.

  1. Nortriptyline was able to normalize the concentration of the protein. In preliminary studies in humans the investigators found that there was a significant improvement of Parkinson’s disease with the use of nortriptyline.
  2. Exenatide, an injection drug for diabetes, has been described to help Parkinson’s patients get better.
  3. Caffeine can also dissolve misfolded alpha synuclein (two compounds from coffee called C8-6-I and C8-6-N). This helps patients with Parkinson’s disease to stabilize.

This is only the beginning of a new approach to Parkinson’s disease and an attempt to cure the disease by dissolving the underlying mechanism. So far the drugs that are in use for Parkinson’s disease are only attempting to stimulate dopamine producing nerve cells to produce more dopamine. But the underlying pathology of accumulating misfolded alpha-synuclein clumps is not yet in the treatment protocol. The new research is different, as it takes this into account in an attempt to prevent the condition.

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