Parkinson’s: Causes – An in-depth look at the development of the disease

The hands tremble as if controlled by another person, the muscles stiffen, the smallest movements become a feat of strength – these are the cardinal symptoms of Parkinson’s disease. The cause of this disease is the death of nerve cells in the brain that release the neurotransmitter dopamine. However, it is not yet known why the cells die. Current research suggests that several factors are involved in the development of this neurodegenerative disease.

In addition to deposits of a defective protein in the affected nerve cells, inflammation, oxidative stress, increased exposure to environmental toxins and sometimes genetic changes also play a role in the development of the disease. We will look for clues in current research to help you understand the possible causes of Parkinson’s disease. This will enable you or your relatives to better understand what happens in the body when you are diagnosed with Parkinson’s disease.

What happens in the brain with Parkinson’s?

The exact mechanisms by which Parkinson’s develops have not yet been clarified. However, it is a fact that nerve cells in the black substance (substantia nigra), an area in the midbrain responsible for the production of the neurotransmitter dopamine, die off. This region, together with the associated areas of the brain (known as the basal ganglia), plays a key role in controlling our movements.

The accelerated cell death in Parkinson’s disease causes a lack of dopamine in the brain, which results in the typical symptoms of Parkinson’s such as tremors, muscle stiffness (rigor) and slower movement (bradykinesia). This is because the neurotransmitter dopamine plays a decisive role in the transmission of signals between the nerve cells and the muscles and ensures that our movements are fluid, purposeful and coordinated. However, if dopamine is in short supply in the brain, this process no longer runs smoothly. This means that muscles can no longer be tensed or relaxed properly.

What are the causes and risk factors of Parkinson’s disease?

The real question now is why these nerve cells die. What are the triggers and risk factors? This is also of interest to scientists who are researching the suspected factors, but the triggering mechanism that sets everything in motion and the exact correlations have not yet been clarified. The following factors play a role in the causes of Parkinson’s disease:

• Deposition of a misfolded protein in the nerve cells of the black matter
• Environmental toxins
• Disturbed intestinal flora
• A misdirected immune system
• Inflammation and oxidative stress in nerve cells
• Age
• Genetic changes
• Medication

Environmental toxins as a cause of Parkinson’s disease

The increase in environmental toxins, to which we are all more or less exposed, appears to play a major role in the development of Parkinson’s disease. In particular, residues of plant protection products (pesticides) and weed killers (herbicides) in conventionally produced food put a strain on the body. Studies have shown that people who are exposed to such chemicals over long periods of time have an increased risk of Parkinson’s disease.

We also ingest heavy metals such as lead or mercury through our food or drinking water, which can also trigger inflammation and malfunctions of the immune system in the body and contribute to the development of neurodegenerative diseases such as Parkinson’s disease.

Malformed proteins put a strain on nerve cells

Researchers have discovered that a protein in the nerve cells of the black matter, known as alpha-synuclein, folds incorrectly in people with Parkinson’s disease. This error in the blueprint is probably due to a genetic mutation (gene change) in the Park1 gene. This gene is responsible for the production of this protein. The protein alpha-synuclein, in turn, is responsible for the release of dopamine. However, as it is now defective, it clumps together and becomes unusable. It is deposited in the nerve cells as a so-called “Lewy body”. This disrupts the normal function of the dopamine nerve cells – they die. The result: dopamine deficiency.

Oxidative stress in nerve cells as a cause of Parkinson’s disease

Oxidative stress plays a central role in the development of Parkinson’s disease. It puts a strain on the cells because the balance between the production of free radicals (oxidants) and the body’s ability to neutralize them (with the help of antioxidants) is disturbed. Free radicals are constantly produced in our body, for example during metabolism. However, if the oxidative stress in our cells becomes too great, our body can no longer cope with it. This leads to cell damage, damage to proteins and even our genes can be attacked. The nerve cells of the black matter in particular suffer from oxidative stress and then perish more quickly.

Oxidative stress in the cells is fueled by factors such as chronic stress, an unhealthy diet high in sugar, white flour and animal foods and low in vegetables, fruit and whole grain products. In addition, environmental toxins from industrial plants, car exhaust fumes and conventionally grown foods, as well as a lack of exercise, trigger oxidative stress in the cells.

Inflammation as a cause of Parkinson’s disease

Oxidative stress and inflammation are mutually dependent. In Parkinson’s disease, chronic inflammatory processes occur that are triggered by the immune system. Certain immune cells, which are normally responsible for removing harmful substances and dead cells, can release inflammatory messenger substances if they are dysregulated. This persistent inflammatory reaction leads to additional oxidative stress in the cells and damage to the nerve cells, particularly in the substantia nigra. As already mentioned, the underlying inflammation and immune cell dysfunction can in turn be triggered by environmental toxins and an unhealthy lifestyle with a lot of stress and an unfavorable diet.

Impaired intestinal flora as a cause of Parkinson’s: does it all start in the gut?

As with many other diseases, the gut and therefore the composition of the intestinal flora also play an important role in the development of Parkinson’s disease. Trillions of microorganisms, mainly bacteria, live in the gut. Put simply, intestinal bacteria can be divided into good intestinal bacteria and bad bacteria. The good bacteria perform important tasks for us, such as producing vitamins, for example certain B vitamins or vitamin K. They also have an anti-inflammatory effect in the body and support our immune system in its defense against pathogens. Science has discovered that a large variety of bacteria, a large number of health-promoting bacteria and a balanced ratio between good and potentially bad bacteria are crucial for good health.

People with Parkinson’s have a disturbed intestinal flora. The bad bacteria, which have a pro-inflammatory effect, for example, have multiplied too much, while the good bacteria with an anti-inflammatory effect are present in too few numbers and in too little diversity. The gut and brain are connected via the “gut-brain axis”. Scientists suspect that Parkinson’s could have its origins in the gut, as protein deposits have also been found in the nerve cells of the stomach and gut in Parkinson’s sufferers. Over time, the protein deposits may have reached the brain.

What role does a misdirected immune system play?

Normally, the immune system protects the brain from infections and repairs damage. In Parkinson’s disease, however, the immune system can be misdirected and mistakenly attack the nerve cells in the substantia nigra. Apparently, the immune system (more precisely the T cells) recognizes the misfolded proteins in the affected cells and triggers their destruction. These autoimmune attacks lead to a chronic inflammatory reaction that further damages the nerve cells and causes them to die.

Genetic changes as a cause of Parkinson’s disease

Heredity as a cause only plays a role in a small proportion of Parkinson’s diseases. An estimated 10 to 15 percent of Parkinson’s cases can be directly attributed to hereditary gene mutations. To date, several genes have been identified which, if they deviate from the norm, are associated with an increased risk of Parkinson’s, including the SNCA gene. This gene is crucial for the production of the protein alpha-synuclein, which in turn controls the release of dopamine. Mutations in the LRRK2, GBA, PARK2, PARK7, PINK1 and PRKN genes have also been observed in Parkinson’s patients.

Mutations in these genes can disrupt various mechanisms, such as protein processing, the function of mitochondria or the detoxification of cells, which ultimately leads to the death of nerve cells. Genetic mutations appear to play a particularly important role in younger patients under the age of 60.

Age as a cause of Parkinson’s disease

Age is the biggest risk factor for developing Parkinson’s disease. Most people are diagnosed when they are over 60 years old. This is because ageing leads to an increase in degenerative processes in the body, which can contribute to the development of the disease, for example:

• The natural, progressive breakdown of nerve cells
• Increased susceptibility to oxidative stress (as the ability to render free radicals harmless decreases)
• The decreasing ability of our body to repair damaged proteins and cells, for example nerve cells in the brain
• Increased risk of malfunctions of the immune system (autoimmune reactions: increasing inability to distinguish own cells from foreign, potentially harmful substances)
• Increased tendency to inflammation

Medication as a trigger for Parkinson’s symptoms

Under certain circumstances, certain medications can contribute to Parkinson’s symptoms becoming noticeable or existing symptoms of Parkinson’s worsening. These drugs usually block the effect of dopamine, which can cause typical Parkinson’s symptoms to appear. These active substances include

• Antipsychotics (neuroleptics) for mental illnesses such as schizophrenia (such as haloperidol and chlorpromazine)
• Lithium for mood swings in bipolar disorders
• Metoclopramide for the treatment of nausea and vomiting
• Prochlorperazine for the treatment of nausea and dizziness
• Calcium channel blockers for the treatment of migraine and dizziness (such as flunarizine and cinnarizine)
• Indomethacin for pain
• Reserpine for the treatment of high blood pressure
• Valproic acid for the treatment of epilepsy
• Aminoglycosides (antibiotics) against infections
• Amiodarone for the treatment of cardiac arrhythmias
• Fluvoxamine for obsessive-compulsive disorder

However, if these medications are discontinued, Parkinson’s symptoms such as tremors, other movement disorders or psychological symptoms such as anxiety usually subside quickly.