What Causes Parkinson’s Disease?
The exact cause(s) of Parkinson’s disease remains unknown. However, research has indicated that there are multiple, interacting destructive processes that cause the dopaminergic neurons — or the main source of dopamine — in the substantia nigra to die in those people that develop Parkinson’s disease. These processes are usually triggered by a genetic susceptibility, oxidative stress, mitochondrial dysfunction and inflammation. This combination of processes selectively and irreversibly destroys vital movement-controlling cells in the substantia nigra, resulting in loss of motor control and a gradual decline in movement and activity.
The good news is that demand for a broader array of effective preventative measures, as well as alternatives to improve the quality of life of those with Parkinson’s disease has led to a steadily growing body of sound research on how to best avoid and manage this disorder.
About 15% of people with Parkinson’s disease has a first-degree relative that also has or had Parkinson’s disease, which suggests that genetics may play a role in the development of the disease. Scientists have identified nine genetic mutations that have been associated with Parkinson’s disease, particularly early onset of Parkinson’s, which is diagnosed before age 40.
The National Human Genome Research Institute, a division of the National Institutes of Health, has compiled further information about the role of genetics and genetic testing in Parkinson’s disease. They can also assist with finding a genetic counselor; their website is: http://www.genome.gov/10001217#4.
Individuals found to have a one or more genetic mutations linked to Parkinson’s disease, as well as those with a family history of Parkinson’s disease or other disorders related to neurotransmitter imbalances should initiate nutritional and lifestyle strategies to combat neurodegeneration.
Oxidative Stress and Parkinson’s Disease
The cause of cell death in neurodegenerative diseases such as Parkinson’s disease remains largely unknown. However, the formation of free radicals and the occurrence of oxidative stress may be a common component of many, if not all, such disorders. For example, in Parkinson’s disease key alterations occur in the substantia nigra in regards to iron handling, mitochondrial function and antioxidant defenses, particularly in regards to reduced glutathione (which is the body’s most powerful antioxidant). These changes dramatically increase oxidative stress and free radical production and are accompanied by evidence of free radical mediated damage in the form of increased lipid peroxidation and damage to the DNA. Increased lipid peroxidation and damage to the DNA causes more and more inflammatory chemicals to be released, initiating a process that perpetuates neurodegeneration.
Based on available research, it is probable that the onset of oxidative stress is a common mechanism by which neuronal death occurs contributing to the progression of Parkinson’s disease. Therefore, therapeutic strategies aimed at limiting free radical production and oxidative stress and/or damage may slow the advancement of Parkinson’s disease.
Mitochondria are the organelles that generate energy within cells, that is why they are often referred to as the ‘powerhouses’ or ‘furnaces’ of the cell. Mitochondria are found in every cell of the human body except red blood cells, and convert the energy from food into energy (specifically, adenosine triphosphate, or ATP) that powers most cellular functions. When mitochondrial dysfunction occurs, energy/ATP is not generated properly resulting in the loss of cellular repair and cellular inefficiency, which research is linking to the pathogenesis of Parkinson’s disease.
Unfortunately, once mitochondrial dysfunction starts, very specific measures are needed to halt the detrimental changes it produces. This is because as mitochondria become dysfunctional they generate large quantities of free radicals, which contribute to oxidative stress that, in turn causes further mitochondrial dysfunction. Oxidative stress causes a loss of mitochondria over time, which means fewer mitochondria are available to meet the energy demands of the cell to repair damaged components. The cascade of mitochondrial dysfunction, oxidative stress and loss of mitochondria forma self-perpetuating process that leads to the dopaminergic cell death associated with Parkinson’s disease.
Numerous studies have identified mitochondrial dysfunction as an underlying cause of both genetic and sporadic Parkinson’s disease. In addition, many of the genes that are linked to familial Parkinson’s are related to mitochondrial function. Several factors, including exposure to environmental toxins and age-related mutations in mitochondrial DNA contribute to mitochondrial dysfunction.
Inflammation contributes to the progression of neurodegeneration in Parkinson’s disease. To understand how we have to first review a little brain immunology.
The brain contains immune cells called microglia. Microglia cells act as the first and main form of active immune defense in the central nervous system. Upon activation, microglia release inflammatory chemicals called cytokines that are designed to combat threats and destroy infectious agents before they damage the sensitive neural tissue. However, these inflammatory chemicals can spread to nearby healthy neurons and cause degeneration. Dopaminergic neurons in the substantia nigra express receptors for these inflammatory chemicals and can be damaged if exposed to them over time.
As dopaminergic cells succumb to either environmentally or genetically induced mitochondrial dysfunction, they release free radicals. These free radicals then activate nearby microglial cells, which excrete more inflammatory chemicals that bind to and damage dopaminergic neurons. This process may continue over years or even decades, slowly causing the loss of dopaminergic neurons that leads to the symptoms of Parkinson’s disease.
How They Tie Together
They human brain requires an enormous amount of blood to support all its metabolic and neurological activity. Fully one-fifth of the blood pumped by the heart goes to the brain. Thus, the neurons in the brain need a constant supply of oxygen and nutrients to function properly.
Unfortunately, neurons in the brain are highly susceptible to free radical damage over time. As stated in the section on oxidative stress this is known to be one of the underlying causes of dopaminergic cell death that leads to many of the symptoms of Parkinson’s disease.
A primary contributor to this oxidative stress is mitochondrial dysfunction. Mitochondrial dysfunction causes the intra-cellular furnaces known as mitochondria to mis-manage energy flow, which results in an excessive production of free radicals.
Oxidative damage leads to inflammation in the brain tissue, which causes additional oxidative stress. The resulting domino effect (oxidative stress -> inflammation ->additional oxidative stress -> more inflammation, etc.) is especially destructive to the vulnerable dopamine-producing cells in the substantia nigra.
Fighting Symptoms of Parkinson’s
While this cascade of events appears to be both progressive and irreversible, recent research and clinical findings have identified interventions that can effectively neutralize oxidative stress and calm the inflammatory processes involved in Parkinson’s disease. This multi-faceted, multi-factorial approach has generated a growing body of interest and research in the world of neuroscience and can be used to prevent and/or halt the progression of the disease.