The researchers recently discovered that dopamine cells in the brain area affected by Parkinson's disease are unable to protect against aging-related damage to the DNA of their mitochondria.
Study leader Dr. Charalampos Tzoulis - a neurologist at the University of Bergen and Haukeland University Hospital, both in Norway - and colleagues hope that the discovery will lead to new treatments for Parkinson's disease. They report the findings in the journal Nature Communications.
Parkinson's is a progressive, brainwasting disease that affects movement and can manifest as a range of symptoms, including: muscle rigidity; speech problems; tremors in the hands, limbs, jaw, and face; and impaired posture, gait, and balance.
Despite decades of research, the exact causes of Parkinson's disease remain a mystery. Experts generally agree that a combination of genetic and environmental factors - both of which vary from person to person - are involved.
An important known risk factor is age. The estimated risk of developing Parkinson's disease is 2-4 percent for people aged 60 and over, compared with 1-2 percent in the general population.
The disease mainly affects dopamine-producing neurons or nerve cells in a brain structure known as the substantia nigra. As the disease progresses, these cells malfunction and die, depleting levels of dopamine, a chemical messenger that plays an important role in controlling movement.
Many scientists believe that a better understanding of the mechanisms behind the destruction of dopamine cells could lead to treatments that stop or even reverse Parkinson's disease.
Aging-related mitochondrial DNA damage
For their study, Dr. Tzoulis and colleagues focused on the mitochondria of dopamine-producing cells. Mitochondria are tiny compartments inside cells that act as powerhouses; they digest nutrients and produce energy-rich molecules for the cell.
- Worldwide, more than 10 million people are affected by Parkinson's disease
- Around 60,000 cases are diagnosed every year in the United States
- Thousands more go undetected.
Mitochondria have their own DNA, separate from the DNA in the cell nucleus, that contains code for building the powerhouses. Dr. Tzoulis explains:
"It is known that the DNA of mitochondria is damaged during aging, causing failure in the power generators, lack of energy, and disease."
The researchers conducted a detailed investigation of mitochondrial DNA in the brains of healthy older people and individuals with Parkinson's disease.
They found that the dopamine-producing cells in the substantia nigra of the healthy brains were able to protect against aging-induced damage to their mitochondrial DNA by producing more healthy DNA.
This replenishment process was much weaker in the diseased brains, resulting in a gradual loss of healthy DNA in the mitochondria of their dopamine cells.
Dr. Tzoulis says he believes that the discovery reveals an important mechanism that normally defends the brain against aging-induced damage. This mechanism appears to malfunction in people who develop Parkinson's disease, leaving their brains more susceptible to the effects of aging. He concludes:
"There is generally very little knowledge about the mechanisms causing Parkinson's disease. Now, we are a step closer to understanding these mechanisms and we may have a target to strike at for therapy."