Molecular mechanism triggering Parkinson’s disease identified

Scientists at the Stanford University School of Medicine have identified a molecular pathway responsible for the death of key nerve cells whose loss causes Parkinson’s disease. This discovery not only may explain how a genetic mutation linked to Parkinson’s causes the cells’ death, but could also open the door to new therapeutic approaches for the malady.

In a study to be published July_29 in Nature, investigators used an animal model, the common fruit fly, to show that the mutation results in impaired activity of recently discovered molecules called microRNAs, which fine-tune protein production in cells. This impairment, in turn, leads to the premature death of nerve cells specifically involved in the secretion of the brain chemical dopamine. The degeneration of these so-called dopaminergic nerve cells in the brain is a hallmark of Parkinson’s.

“MicroRNA, whose role in the body has only recently begun to be figured out, has been implicated in cancer, cardiac dysfunction and faulty immune response,” said Bingwei Lu, PhD, associate professor of pathology and the study’s senior author. “But this is the first time it has been identified as a key player in a neurodegenerative disease.”

Parkinson’s is a movement disorder characterized outwardly by tremor, difficulty in initiating movement, and postural imbalance and, in the brain, by a massive loss of the dopaminergic nerve cells in areas that fine-tune motor activity. It affects an estimated 1 million people in the United States. The incidence of Parkinson’s, rare in younger people, increases dramatically with age, although nobody is sure why. Nor is it known why the most common mutation implicated in Parkinson’s – LRRK2 G2019S, found in about one-third of all Parkinson’s cases occurring among North African Arabs and North American Ashkenazi Jews – increases the likelihood of contracting the disease.

The new findings show that the LRRK2 mutation trips up the normal activity of microRNAs, resulting in the overproduction of at least two proteins that can cause certain cells, like brain cells, to die.

Source: Stanford University Medical Center, USA



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