Researchers at Brigham and Women’s Hospital have made significant progress in understanding neurological diseases by studying circular RNAs (circRNAs) in brain cells. In a recent study, the team identified over 11,000 distinct RNA circles associated with brain cells involved in Parkinson’s disease and Alzheimer’s disease.
Circular RNAs were previously considered insignificant, but the findings indicate that they play a crucial role in programming human brain cells and synapses. The researchers discovered that circular RNAs are abundantly produced by brain cells, including those linked to neurodegenerative disorders.
To conduct the study, the researchers utilized laser-captured neurons from postmortem human brain samples. They used ultra-deep, total RNA sequencing to examine the genetic code of circular RNAs in two cell types: neurons and non-neuronal cells. Their analysis revealed that 61% of the synaptic circRNAs were associated with brain disorders.
The team identified numerous cell-type specific circular RNAs in dopamine and pyramidal neurons, which are essential for motor control, mood, motivation, memory, and language. Surprisingly, the circular RNAs defined neuron identity more effectively than the linear RNAs produced from the same gene locations.
The study also highlighted the connections between circular RNAs and specific diseases. A significant number of genes associated with Parkinson’s and Alzheimer’s disease were found to produce circular RNAs. For instance, a circRNA derived from the Parkinson’s gene DNAJC6 exhibited reduced expression in vulnerable dopamine neurons even before the onset of symptoms.
The researchers believe that naturally occurring circRNAs could serve as biomarkers for identifying specific brain cells involved in the early stages of neurological diseases. circular RNAs are highly stable and can be utilized as reporters and for delivering therapies. The team also suggests that circRNAs can be synthesized synthetically and used as RNA medicines in the future.
While the study provides the most extensive analysis of circRNAs in human brain cells to date, there are still limitations. The researchers acknowledge the need for further research to comprehend how circRNAs function and the genetic regulators that govern their behavior.
Overall, these findings offer valuable insights into the molecular mechanisms underlying neurodegenerative disorders. Circular RNAs have the potential to revolutionize RNA diagnostics and serve as therapeutic targets for neurological conditions.
Source: Brigham and Women’s Hospital