Circular Logic of RNAs in Parkinson Disease
Published:12 Oct.2023 Source:Brigham and Women Hospital
A new study by investigators from the Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, identified over 11 000 distinct RNA circles that characterized brain cells implicated in Parkinson's disease and Alzheimer's disease.
They laser-captured neurons from 190 frozen postmortem human brain samples. They found that 61% of all synaptic circRNAs they characterized were associated with brain disorders. Notably, they found 4,834 cell-type specific circular RNAs in dopamine and pyramidal neurons, two highly functioning brain cells. Degeneration of these dopamine and pyramidal neurons plays a key role in the development of neurological disorders. When researchers investigated this connection further, they found that a surprising number of Parkinson's and Alzheimer's genes produced circular RNA.The team identified that genes associated with different diseases produced circRNAs in particular cell types.
Current findings provide the most comprehensive analysis of circRNAs in human brain cells to-date and suggest they can be leveraged for RNA diagnostics and medicines used to treat neurological conditions. Limitations of the current study include an incomplete understanding of how this complex RNA machinery specifies neuron and synapse identity. Future research can investigate how these circRNAs arise and function and survey additional genetic regulators that govern their behavior.