A recent study could change our understanding of the ways in which mitochondria, or the powerhouses of the cells, influence Parkinson's disease. The latest results fly in the face of current theories.

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Mitochondria (shown here) turn nutrients into energy that the cell can use.

Parkinson's disease is one of the most common neurodegenerative conditions in the United States, and it affects an estimated 1 million people there, plus 10 million worldwide.

The disease causes a gradual impairment of motor skills, with symptoms including tremor and rigidity. Parkinson's can also lead to dementia, depression, and anxiety.

The primary changes in the Parkinson's disease-affected brain occur in a small region called the substantia nigra. These dopamine-producing neurons die off, and the region is infiltrated by so-called Lewy bodies, which are abnormal aggregates of protein.

Despite years of research, the mechanisms that underly Parkinson's disease are unknown. However, recent research implies that mitochondrial dysfunction might be involved.

Parkinson's and mitochondria

In the early 1980s, researchers found that when an enzyme called mitochondrial complex 1 (MC1) was inhibited, neurons in the substantia nigra broke down, causing Parkinson's-like symptoms.

Mitochondria are responsible for turning the nutrients we consume into ATP, which is the energy currency of the cell. MC1 is one of many enzymes involved in this complex process.

In the late 1980s, scientists found that MC1 levels were reduced in the brain regions most affected by Parkinson's disease. This finding has been reproduced and is now well-established: many have theorized that, because MC1 levels drop in the substantia nigra of people with Parkinson's, it might be responsible for neuronal death.

However, to date, the meaning of reduced MC1 has remained a mystery. Are MC1 levels the reason why the neurons are dying, is it a protective mechanism sparked by neuronal cell death, or is it simply a symptom of dying neurons?

Many studies that chose to look at the levels of MC1 in the substantia nigra did not compare them with other parts of the brain. So, recently, scientists from the University of Bergen (UiB) in Norway set out to investigate levels of this enzyme in other parts of the Parkinson's-affected brain.

MC1 throughout the brain

The researchers — led by Charalampos Tzoulis, from the Department of Clinical Medicine at UiB — thought that if MC1 reduction is the primary reason for neuronal breakdown in Parkinson's disease, it should only be reduced in those areas affected by it, remaining at normal levels in the rest of the brain.

To find out whether or not this was the case, they took brain tissue from 18 people with Parkinson's and matched them with 11 healthy control individuals. Their findings are published this week in the journal Acta Neuropathologica.

They discovered that MC1 was, in fact, reduced throughout the entire brain, and it did not correlate with the death of neurons. Parts of the brain that were relatively untouched, such as the cerebellum, still had much lower levels of MC1.

"This new study shows that complex 1 deficiency is, in fact, a global phenomenon in the brain of persons with Parkinson's disease, and is found indiscriminately in both affected and healthy brain regions."

Charalampos Tzoulis

"Intriguingly," he adds, "brain cells (neurons) with decreased complex 1 levels are significantly less likely to contain Lewy bodies, the abnormal protein-aggregates that characterize Parkinson's disease."

The conclusion is that reduced levels of MC1 are not necessarily harmful to the brain or involved in cell death — if anything, reduced levels may be protective.

As Tzoulis explains, "It is possible that complex 1 deficiency is part of a compensatory regulation attempting to protect the brain in Parkinson's disease, for instance via decreased production of oxidative free radical species."

These preliminary findings will need to be confirmed, and if they are, it could open up new avenues of research. If MC1 reduction is, in fact, a protective mechanism, perhaps it could be exploited to design the Parkinson's drugs of the future.