Parkinson's: 'Genetic switch' may play key role in preserving brain cells

Written by Catharine Paddock PhD

Published: Friday 17 February 2017

The discovery of a "genetic switch" that helps to maintain the health of brain cells could lead to new treatments that could delay or even prevent the symptoms of Parkinson's disease.

The researchers used fruit flies carrying mutant forms of PINK1 and PARKIN genes to search for other genes involved in Parkinson's disease.

Image credit: Miguel Martins, University of Leicester

So conclude researchers at the University of Leicester in the United Kingdom, who led a new study published in the journal Cell Death and Differentiation.

Worldwide, more than 10 million people are living with Parkinson's disease, a progressive brainwasting disorder that affects movement.

Parkinson's disease gives rise to symptoms that include: muscle rigidity; impaired gait, balance, and posture; tremors in the limbs, hands, face, and jaw; and problems with speech.

The disease primarily impacts a part of the brain called the substantia nigra, where it gradually destroys vital brain cells, or neurons, that produce dopamine - a chemical messenger that is essential for controlling movement.

The loss of dopamine-producing cells can happen for a number of reasons, but in some hereditary cases of Parkinson's disease, it can result from unhealthy mitochondria - tiny compartments inside cells that provide them with energy to function and stay alive.

Genetic switch controls mitochondrial health

Some hereditary forms of Parkinson's disease are caused by mutations in the genes PINK1 and PARKIN, which play an important role in maintaining the quality and integrity of mitochondria.?

For their study, the team used fruit flies because they offer a good model for investigating the genetic and molecular processes of human diseases. The insects carry around 75 percentof the genes that cause human disease.

For example, fruit flies with mutations in PINK1 and PARKIN also show hallmarks of Parkinson's disease - they have weak muscles, struggle to fly, move slowly, and lose dopamine cells in their brains. They also accumulate defective mitochondria.

The researchers used fruit flies carrying mutant forms of PINK1 and PARKIN genes in order to search for other genes involved in Parkinson's disease.

Using an approach called bioinformatics, they discovered that a gene called ATF4 is vital for mitochondrial health; it acts as a switch for increasing or decreasing the activity of PINK1 and PARKIN.

Study leader Dr. Miguel Martins, of the MRC Toxicology Unit at Leicester, explains that when ATF4 expression was reduced in the fruit flies, it also reduced expression of PINK1 and PARKIN, leading to "dramatic locomotor defects, decreased lifespan, and dysfunctional mitochondria in the brain."

The team also found that overexpression of these mitochondrial genes in fruit fly models of Parkinson's disease re-established mitochondrial function and averted loss of brain cells.

By finding the gene networks that orchestrate the mitochondrial processes that keep brain cells healthy, the team believes that they have identified a number of new targets for the treatment of Parkinson's disease.

"Studying the roles of these genes in human neurons could lead to tailored interventions that could one day prevent or delay the neuronal loss seen in Parkinson's."

Dr. Miguel Martins

http://www.medicalnewstoday.com/articles/315909.php