What is Parkinson’s disease?
Parkinson’s disease is a progressive, neurodegenerative movement disorder. It worsens over time, and it is caused by the degeneration of nerve cells in the brain. The most prominent symptoms of Parkinson’s disease affect movement, although many other symptoms may also occur, some of which can be even more disabling than the movement symptoms.
Estimated seven to 10 million people worldwide, and as many as one million individuals in the United States live with PD. Approximately 60,000 Americans are diagnosed annually; incidence increases with age. (source: Parkinson’s Disease Foundation).
What is the role of mitochondrial dysfunction in Parkinson’s disease?
Scientists have accrued a large body of evidence confirming that mitochondria play an important role in the development of Parkinson’s disease. The most prominent symptoms of Parkinson’s disease are muscle trembling and weakness, which then progress to muscle immobility. These symptoms are the result of a decline of dopamine in the brain, which occurs as a result of loss of neurons that produce this vital neurotransmitter.
Mutations to mitochondria directly affect a cell’s ability to make dopamine. Damaged mitochondria can negatively influence neurons – including those that produce dopamine – in many ways. For example, they can cause overproduction of free radicals that can damage the cells; they can affect calcium regulation within the cells and the intracellular spaces, which directly affects neuronal health; they can create problems with axonal transport (the way nerve cells communicate with each other); and they can cause cell death. All of these aspects can contribute to malfunction or death of dopamine-producing neurons.
Mutations to mitochondria can occur through exposure to environmental toxins, such as medications or pesticides, or they can occur as a result of genetics – both inherited and acquired mutations. To further complicate the interplay between mitochondria and Parkinson’s disease, pathways of disease can affect mitochondria directly, such as through direct genetic mutations, or indirectly, by affecting a substance upstream from the mitochondria that interferes with its normal functioning.
The economic impact of Parkinson’s disease is significant. The National Institute of Neurological Disorders and Stroke (NINDS) estimates that Parkinson’s disease carries an annual cost of over $5.6 billion to our society, including both direct medical expenses and indirect costs such as lost income, disability payments and medical costs.
Parkinson’s disease (PD) is a common and disabling neurodegenerative disease marked by progressive motor dysfunction, which results from selective degeneration of the nigrostriatal pathway. Complex I defects may result in oxidative stress and increase the susceptibility of neurons to excitotoxic death. In this way, environmental exposures and mitochondrial dysfunction may interact and result in neurodegeneration.
Recent findings implicate mitochondrial dysfunction, oxidative damage, abnormal protein accumulation and protein phosphorylation as key molecular mechanisms compromising dopamine neuronal function and survival as the underlying cause of pathogenesis in both sporadic and familial PD.
Mitochondrial dysfunction may not be the only cause of Parkinson’s disease, but interventions focused on improving mitochondrial function are showing positive progress. Several studies have been performed using agents that influence mitochondrial function, including the use of dopamine agonists (similar to dopamine) and Coenzyme Q10 to replace or boost the function of the patient’s mitochondria. Researchers also are exploring different avenues of treatment for individuals with Parkinson’s disease in which mitochondrial dysfunction has been noted. Current treatment relies on the replacement of dopamine. However, this does not reverse the loss of neurons or further progression of the disease. Researchers are targeting mitochondrial function as a way to alter this key component of the disease.