APDA-funded Brigham and Women’s Hospital explores the genetic variants associated with Parkinson’s disease and other neuropsychiatric conditions

In classic biochemistry, ribonucleic acid (RNA) was thought to be a simple middle man between our genome and our proteins. Recently, however, it has become clear that RNA exists in multiple forms and plays a myriad of roles, including regulating protein production, regulating genome activity, and sensing environment. In fact, only a very small portion of DNA gets transcribed into RNA that creates protein. A much large portion gets transcribed into RNA that has various other functions.

Dr. Xianjung Dong, an APDA-funded researcher, working in the laboratory of Dr. Clemens Scherzer, Director of APDA’s Center for Advanced Research at Brigham and Women’s Hospital and Harvard Medical School, conducted a massive analysis whose goal was to create a complete inventory of all RNAs in dopamine producing neurons in human brain. Dopamine neurons are important in many diseases including Parkinson’s disease (PD), schizophrenia and addiction. These neurons work sluggishly in PD, but are hyperactive in schizophrenia.

The project identified over 70,000 RNA “parts” in dopamine neurons. The team found that 64% of the genome actively produces RNA in the dopamine neurons, the vast majority of which does not code proteins, but might have roles in regulating how dopamine neurons work. This opens up a massive treasure trove of information about the dopamine neurons, not studied before, that could link to disease.

Interestingly, the team found that glitches in the genome associated with increased risk of PD, schizophrenia or addiction, were linked to these newly found regulatory RNAs — much more so than to protein-producing RNAs. These results were recently published in Nature Neuroscience.

The team has generously made the compendium of all the RNA transcribed in dopamine neurons publicly available at http://www.humanbraincode.org. The data can therefore be used by other investigators to further their work. “This is very useful for pharmaceutical companies, who need to check whether the targets for their new PD drugs are actually present in dopamine neurons of patients’ brains”, says Scherzer. “Now, they can simply type their favorite drug target into the webportal and it will tell them immediately, whether the drug is actually hitting a target in these key Parkinson’s cells or not”.

APDA is proud to support such ground-breaking work and salutes Dr. Scherzer and his team for their achievement.