Researchers at King’s College London have identified a gene, HIFalpha, that plays a role in the regulation of nerve signals from damaged mitochondria that, in turn, affect nerve cell function, and which holds out the possibility of eventually finding a way to turn that gene off and restore function. The study, entitled “Mitochondrial retrograde signaling regulates neuronal function,” was published in The Proceedings of the National Academy of Sciences (PNAS).
Researchers used Drosophila melanogaster (fruit fly), a popular model organism for genetic studies with parallels in human disease genetics, to study the impact of mitochondrial defects on neuronal function. Mitochondria are responsible for cellular energy production, and previous studies have connected their function to the pathogenesis of a number of neurodegenerative diseases, including Parkinson’s. The neuronal processes underlying the development of these conditions, however, has not been well understood.
In this study, scientists discovered that mitochondrial defects lead to impairment of nerve cell function in fruit flies, essentially stopping the cells from working as they should. They also identified HIFalpha as the genetic regulator of the signals sent by the damaged mitochondria. Upon findings of nerve cell dysfunction, the researchers essentially turned off the HIFalpha gene expression, and nerve function in the fruit flies was restored. They found that deactivation of the HIFalpha gene before symptoms developed prevented nerve cell loss of function.
“Like their human counterparts, flies with Parkinson’s disease progressively lose motor function, which includes a negative impact on their ability to climb. Remarkably, we found that switching off a particular gene dramatically improved their motor function and climbing ability,” said Dr. Joseph Bateman, with the Institute of Psychiatry, Psychology & Neuroscience at King’s College London. “The biggest surprise from our work is that damaged mitochondria produce a signal that actively prevents nerve cells from working properly.”
In addition to understanding the elusive genetic mechanisms of pathogenesis at play, these new findings could mean a completely new avenue of therapy to treat and prevent Parkinson’s disease. This is especially important because current Parkinson’s disease therapies treat early symptoms of the disorder but progressively lose effect as the condition progresses, and do not address Parkinson’s underlying causes.
Read More Recent News
Burlington, Massachusetts-based, medical market research firm Decision Resources Group (DRG) reports, citing analyses of U.S. longitudinal patient-level claims data, that the Parkinson’s disease (PD) drug treatment algorithm remains highly stable, with levodopa (either alone or in combination with carbidopa) as its foundation.