APDA supports groundbreaking research into Circular RNA and its role in brain health and disease

In a recently published study, a team of researchers at Brigham and Women’s Hospital, spearheaded by Drs. Xianjun Dong and Clemens Scherzer, studied an under-explored type of RNA, called circular RNA (circRNA) and its relationship to brain disease.

APDA is proud to have supported this work of Dr. Dong as a recipient of an APDA Research award. APDA is also honored to fund the APDA Center for Advanced Research at Brigham and Women’s Hospital, with Dr. Scherzer as the Director. Dr. Scherzer is a member of APDA’s Scientific Advisory Board.

In the nucleus of the cell, DNA can be transcribed into various types of RNA, which then are able to leave the nucleus and play a variety of roles within the cell. Most of our understanding of RNA focuses on linear RNA which is translated into proteins. CircRNA, a type of RNA that is also produced from DNA and exists in a highly stable circular format, has typically been thought of as unimportant and not critical to cell function. However, there are indications that circRNA is worthy of a closer look. Thousands of circRNAs are prominently enriched in brain tissue, especially around the synapse, the space between one neuron and the next. Importantly, synaptic dysfunction, or the inability for one neuron to communicate with its neighbors is emerging as an early sign of PD, preceding the onset of neuronal death. Drs. Dong, Scherzer and colleagues therefore sought to understand the role of circRNA and whether certain circRNAs are associated with development of neurologic disease such as Parkinson’s disease.

To that end, they sequenced all the circRNAs in two specific types of neurons, dopamine neurons and pyramidal neurons, as well as non-neurons, from 190 human brain samples. They found more than 11,000 different types of circRNA. Interestingly, particular circRNAs were over-represented in specific types of cells, thereby defining that cell type’s identity. Researchers then analyzed the specific DNA sequences that were transcribed into circRNA and found that these included a high number of genes associated with Alzheimer’s disease and Parkinson’s disease. DNA sequences associated with synaptic function were also commonly used as templates for circRNA.

Because the circRNAs are much more stable than linear RNA and because they appear to be tied to genes associated with disease, there is potential for them to be used as biomarkers of disease. There is also much that is not yet understood about this intriguing set of molecules. This paper opens up a whole field of research into further understanding circRNA in health and disease.

We are very proud to have supported this seminal work and look forward to further discoveries from this team. “This work is a direct result of my 2019 APDA Research award. Thanks again for the ongoing support from APDA!!” says Dr. Dong. Dr. Scherzer added “Great thanks for all the APDA’s support for this work!” 

You can learn more about APDA-funded research here.