Researchers have discovered that a molecule already known to be important for other cell functions may also serve as a target against Lewy bodies, which are the toxic protein deposits that build up in the brain in Parkinson’s disease.

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Understanding why brain cells die is key for treating Parkinson’s.

The molecule, called cardiolipin, is an essential membrane component of mitochondria, which are the tiny powerhouses inside cells that give them energy and help drive their metabolism.

Lewy bodies are one hallmark of Parkinson’s disease. They contain toxic clusters of alpha-synuclein and other proteins that have not folded properly.

In a paper now published in the journal Nature Communications, researchers from the University of Guelph in Canada describe how they discovered “a novel mechanism” in which cardiolipin folds alpha-synuclein.

They also found that cardiolipin “can pull” alpha-synuclein out of the toxic clusters and refold it, “thus effectively buffering,” or delaying, the progress of the protein’s toxicity.

“Identifying the crucial role cardiolipin plays,” notes senior study author Scott D. Ryan, who is a professor from the university’s Department of Molecular and Cellular Biology, “in keeping [alpha-synuclein] functional means cardiolipin may represent a new target for development of therapies against Parkinson’s disease.”

Parkinson’s disease is a brain-wasting disorder that gets worse over time. The condition’s most common symptoms include tremors, muscle rigidity, impaired balance and coordination, and slowness of movement.

It also has symptoms not related to movement, which include — but are not limited to — anxiety, depression, sleep disturbance, constipation, and fatigue.

There are more than 10 million people living with Parkinson’s worldwide, including around 1 million in the United States and 100,000 in Canada.

The disease mostly strikes after the age of 50, although in 10 percent of cases, it can arise earlier.

The main difference between Parkinson’s disease and other movement disorders is that the former is caused by the death of dopamine-producing cells in the substantia nigra region of the brain.

Dopamine is a messenger molecule, or neurotransmitter, that helps to control movement. Many treatments for Parkinson’s aim to raise brain levels of dopamine.

Although incorrectly folded alpha-synuclein is a feature of Lewy bodies — whose presence precedes the death of dopamine cells in Parkinson’s disease — the specific mechanism is somewhat unclear.

However, what we do know is that it in its normal form, alpha-synuclein seems to be important for healthy functioning in cells.

For instance, there is evidence to suggest that alpha-synuclein is important for neurotransmitter storage and recycling, and it may also have a role in the control of enzymes that raise levels of dopamine.

In order to find out how brain cells deal with incorrectly folded alpha-synuclein, Prof. Ryan and his colleagues carried out experiments using human stem cells.

“We thought,” says Prof. Ryan, “if we can better understand how cells normally fold alpha-synuclein, we may be able to exploit that process to dissolve these aggregates and slow the spread of the disease.”

The researchers compared normal stem cells with those from people with Parkinson’s disease who carried a mutated version of the alpha-synuclein gene.

Through these experiments, the team discovered that alpha-synuclein attaches to mitochondria inside brain cells, and that the cardiolipin in the mitochondria refolds the protein into non-toxic forms, thus delaying the process of alpha-synuclein toxicity.

The scientists also found that the “buffering capacity is reduced” in cells that had the mutated forms of alpha-synuclein that lead to familial Parkinson’s disease.

Thus, the researchers suggest that the ability of cardiolipin to slow or halt the progress of alpha-synuclein toxicity is eventually overwhelmed and leads to the death of cells in people with Parkinson’s disease.

They believe that their results could lead to a new drug that slows the progression of the disease by targeting cardiolipin’s role in the folding of alpha-synuclein.

“The hope is,” says Prof. Ryan, “that we will be able to rescue locomotor deficits in an animal model. It’s a big step towards treating the cause of this disease.”

Based on this finding, we now have a better understanding of why nerve cells die in Parkinson’s disease and how we might be able to intervene.”

Prof. Scott D. Ryan