Parkinson’s patients might find hope in study that unravels effects of vitamin K2 on fruit flies

NIU researchers part of team publishing in Science

Rangaswamy “Nathan” Meganathan

Rangaswamy “Nathan” Meganathan

A team of researchers that included two Northern Illinois University scientists has used vitamin K2 to successfully undo the effect of one of the genetic defects that leads to Parkinson’s disease.

The research study, conducted on fruit flies, is published in the latest edition of the prestigious journal Science on its Science Express website (see abstract).

The team included NIU Department of Biological Sciences professor and noted vitamin K expert Rangaswamy “Nathan” Meganathan, as well as his former student, Janaka N. Edirisinghe, who completed his Ph.D. in December. The two collaborated with 10 other scientists from two Belgian institutions, the VIB Center for Biology of Disease and the Center for Human Genetics and Leuven Research Institute for Neurodegenerative Diseases at the University of Leuven.

Study leader Patrik Verstreken, a neuroscientist associated with the Belgian centers, said the discovery gives hope to Parkinson’s patients.

“It appears from our research that administering vitamin K2 could possibly help patients with Parkinson’s. However, more work needs to be done to understand this better,” Verstreken said.

Janaka Edirisinghe

Janaka N. Edirisinghe

Vitamin K2plays a role in the energy production of defective mitochondria, the researchers said. If cells were likened to small factories, then mitochondria would be the power plants responsible for supplying the energy for their operations. They generate this energy by transporting electrons.

In Parkinson’s patients, the activity of mitochondria and the transport of electrons have been disrupted, resulting in the mitochondria no longer producing sufficient energy for the cell. This has major consequences as the cells in certain parts of the brain will start dying off, disrupting communication between neurons. The results are the typical symptoms of Parkinson’s: lack of movement (akinesia), tremors and muscle stiffness.

The exact cause of this neurodegenerative disease is not known. In recent years, however, scientists have been able to describe several genetic defects (mutations) found in Parkinson’s patients, including the so-called PINK1 and Parkin mutations, which both lead to reduced mitochondrial activity. By studying these mutations, scientists hope to unravel the mechanisms underlying the disease process.

Fruit flies (Drosophila) are frequently used in lab experiments because of their short life spans and breeding cycles, among other things. Within two weeks of her emergence, each female is able to produce hundreds of offspring. By genetically modifying fruitflies, scientists can study the function of certain genes and proteins.

Verstreken and his team used fruit flies with a genetic defect in PINK1 or Parkin that is similar to the one associated with Parkinson’s. They found that the flies with a PINK1 or Parkin mutation lost their ability to fly.

Upon closer examination, they discovered that the mitochondria in these flies were defective, just as in Parkinson’s patients. It was also discovered that a gene known as  UBIAD1/Heix, when mutated, enhanced the lethality of PINK1. Because of the defects in the mitochondria, the flies generated less intracellular energy – energy the insects needed to fly.

When the mutant flies were fed vitamin K2, or when UBIAD1/Heix gene was reintroduced, the energy production in their mitochondria was restored and the insects’ ability to fly improved. The researchers were also able to determine that the energy production was restored because the vitamin K2 had improved electron transport in the mitochondria. This in turn led to improved energy production.

The NIU scientists contributed to the project by analyzing samples and providing bacterial mutants that were utilized in these experiments.

“This study provides us with a better understanding of Parkinson’s, and our hope it that our findings will ultimately be helpful to those suffering from the disease,” Meganathan said.

Meganathan, a Distinguished Research Professor at NIU and world expert on vitamin K, has been shedding new light on scientists’ understanding of the vitamin’s biosynthesis for much of his long career.

“We have learned, especially in recent years, that vitamin K deficiencies appear to be linked to a number of inherited diseases in humans, such as certain types of bladder cancer and eye diseases,” Meganathan said.

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