Parkinsons Disease Causes

The exact cause of Parkinson’s disease is unknown. Neither is it clear what causes the degeneration or death of dopamine-neurons in patients suffering from Parkinson’s disease.

Dopamine levels in a normal and a Parkinson's affected  neuron.

The Dopamine Connection

Dopamine is a chemical that is deficient in the brains of people suffering from Parkinson’s disease. PD results when the brain cells that produce dopamine die or degenerate.

When around fifty to sixty percent of the dopamine-producing neurons in the mid-brain have died, patients may exhibit some symptoms of PD. Symptoms of Parkinson’s disease become more pronounced in patients who have lost up to eighty percent of their brains’ dopamine-producing cells.

What Are Neurotransmitters?

Dopamine is one of three main neurotransmitters called “catecholamines”. Neurotransmitters are chemical “messengers” that transmit impulses across the synapses (gaps) between neurons in the brain and onward to the muscles.

Dopamine-neurons (also called dopaminergic neurons) form a network of small clusters, found in several regions of the brain. The main concentration of dopaminergic neurons responsible for controlling muscle movement, emotional, motivational behavioral mechanisms is located in the upper brain stem (mid-brain), in an area called the substantia nigra.

Rotenone and Environmental Causes of Parkinson’s Disease

Findings from several studies suggest that exposure to toxic agro-chemicals, such as the fish chemical and common pesticide rotenone may cause the onset of Parkinson’s disease. Research, for example, involving rats has shown that long-term exposure to pesticides causes brain cell death and the development of symptoms characteristic of Parkinson’s disease. Various studies in recent years have all pointed to a link between chronic exposure to toxic chemicals and pesticides and an increased risk of developing Parkinson’s disease.

One of these studies, published in the scientific journal, Nature Neuroscience (December 2000), found that rats regularly exposed to rotenone developed distinct symptoms of PD, including tremors and loss of muscle control. Significantly, the rats exposed to rotenone also developed Lewy bodies (spherical lumps found in dying brain cells), which are commonly associated with Parkinson’s disease.

Such results, although encouraging, have yet to establish rotenone as a specific cause of Parkinson’s disease in humans.

Findings from the rotenone study led by Professor Greenamyre of Emroy University, Atlanta, Georgia, reported in Nature Neuroscience (December 2000) “indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of Parkinson’s disease.”

Lewy Bodies: The Link with Parkinson’s Disease

The main characteristics of Parkinson’s disease are dopaminergic cell degeneration and the presence of neuronal, intercellular, sphere-shaped structures in the brain cells called Lewy bodies. Lewy bodies are made up of microscopic, dense deposits of abnormal protein, formed as products of the mutated alpha-synuclein gene.

Further research is required into the possible link between Lewy bodies and their role in the development of Parkinson’s disease. Scientists have yet to establish whether Lewy bodies are the primary cause of dopaminergic neuronal death or are merely instrumental in the progressive cell degeneration associated with Parkinson’s disease and/or the aging process, in general. One line of thought suggests that Lewy bodies may, in fact, act as a defense mechanism against the production of abnormal proteins in the brain and the loss of dopamine cells. Studies involving the function and make-up of Lewy bodies are ongoing.

Interestingly, Lewy bodies have been identified at autopsy in a significant percentage of older people who have not been diagnosed with Parkinson’s disease. This discovery has prompted scientific speculation that the development of Lewy bodies might indeed be a natural part of the aging process. One study for example, found Lewy bodies in around thirteen percent of subjects over the age of seventy, increasing to sixteen percent in the eighty plus age group.

Genetic Causes of Parkinson’s Disease

Recent research has identified a hereditary link where close relatives of Parkinson’s disease patients are twice as likely to develop Parkinson’s disease as people with no family history of PD. The extent to which other environmental factors may also play a part in genetic predisposition to Parkinson’s disease remains unclear.

Key Genes and the Onset of Parkinson’s Disease

A number of studies have identified a link between certain genes and a predisposition to early-onset Parkinson’s disease, including alpha-synuclein (SNCA), parkin and ubiquitin CH-L1. The most common genetic form of PD results from mutations in the parkin gene. A number of different parkin mutations exist, some of which result in an early-onset and aggressive form of Parkinson’s.

Research into the genes that may be associated with late-onset Parkinson’s disease is less advanced, but potential suspects include N-acetyl-transferase 2, a gene involved in the processing of toxins in the body, and the complex 1 gene, a mitochondrial chromosome.

Parkinson’s Disease and Mitochondria

Mitochondria, present in most types of cells, are specialized entities with their own unique DNA and genetic structure. The function of mitochondria is to produce and transfer energy. Research has shown that variants of the mitrochondrial genes may cause the onset of Parkinson’s disease.

Other Potential Causes of Parkinson’s Disease

Other factors that may trigger the onset of Parkinson’s disease include:

  • viral infection
  • high concentrations of damaging free-radicals in the body
  • excess iron and manganese in the diet, which tends to accelerate the oxidation process and degeneration of the brain cells involved in Parkinson’s disease
  • diseases of the brain including brain tumors, hydrocephalus, encephalitis, meningitis and stroke
  • trauma and swelling in the brain caused by hard blows to the head
  • use of antipsychotic drugs and IV drug abuse of MPTP which inhibits the function of mitochondria within the nerve cells of the brain
  • carbon monoxide poisoning.

Resources

American Academy of Neurology. (2003). Parkinson’s disease linked to high iron intake.

Atkins, L. (2000). Can you catch Parkinson’s? The Guardian.

Carson-De Witt, R. (2003). Parkinson’s disease.

National Library of Medicine. (2004). Parkinson’s disease. MedlinePlus Medical Encyclopedia.

National Institute of Neurological Disorders and Stroke (2005). Parkinson’s disease: Hope through research [NIH Publication No. 94-139].

ScienceDaily. (2003). Major new finding on genetics of Parkinson’s disease zeroes in on activity of alpha synuclein.

Verrengia, J.D. (2000). Rotenone pesticide exposure linked to Parkinson’s. Associated Press.