A molecular pathway that causes the death of key nerve cells whose loss triggers off Parkinson's disease had been identified by scientists.
The researchers in Lu's lab conducted their experiments in Drosophila, the fruit fly, to show that the mutation results in impaired activity of recently discovered molecules called microRNAs, which fine-tune protein production in cells.
AdvertisementThis 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."
The researchers looked at the mRNAs containing the genetic recipes for the two overproduced proteins, and predicted that they would be bound by two specific microRNAs: let-7 and miR-184.
The researchers showed that toning down the levels of these two proteins,in itself, prevented dopaminergic nerve cell death in the flies.
"The flies no longer got symptoms of Parkinson's," said Lu.
"This alone has immediate therapeutic implications. Many pharmaceutical companies are already making compounds that act on these two proteins, which in previous studies have been shown to be associated with cancer. It may be possible to take these compounds off the shelf or quickly adapt them for use in non-cancer indications such as Parkinson's."
The study will be published July 29 in Nature.