A groundbreaking discovery by South Korean researchers has unveiled the critical role of RNA editing in regulating neuroinflammation, a key pathological feature of Parkinson’s disease.
On Sunday, the Korea Advanced Institute of Science and Technology (KAIST) announced that a research team led by Professor Choi Minee from the Department of Brain and Cognitive Sciences, in collaboration with the UCL National Hospital for Neurology and Neurosurgery and the Francis Crick Institute in the UK, has demonstrated that the RNA editing enzyme ADAR1 plays an important role in regulating the immune responses and plays a key role in the pathological progression of Parkinson’s disease in astrocytes that cause inflammatory reactions to protect the brain.
Professor Choi’s team developed a cellular model using stem cells derived from Parkinson’s patients, comprising astrocytes and neurons that help nerve cells in the brain and observed the inflammatory responses in brain immune cells after introducing α-synuclein aggregates known to cause Parkinson’s disease.
The study revealed that α-synuclein oligomers, an early pathological form of the protein, activate toll-like receptors in astrocytes, which act as cellular danger sensors. These oligomers also trigger the interferon signaling pathway, a key component of the immune response against pathogens.
During this process, the researchers observed the expression of the RNA editing enzyme ADAR1, which transforms into isoforms that alter protein properties, including their function and structure.
Notably, the team identified that ADAR1’s RNA editing activities, which typically regulate immune responses during viral infections, were specifically modifying genetic instructions through A-to-I RNA editing, changing adenosine (A) to inosine (I).
This finding indicates an abnormal concentration of RNA editing activity on inflammation-triggering genes rather than under normal conditions. The phenomenon was consistently observed in both differentiated neurons from patient-derived stem cells and post-mortem brain tissues of Parkinson’s patients.
The research demonstrates that dysregulation of RNA editing induces chronic inflammatory responses in astrocytes, potentially leading to neuronal toxicity and disease progression.
This study’s significance lies in its novel revelation of RNA editing regulation within astrocytes as a key mechanism in neuroinflammatory responses. It also suggests ADAR1 as a promising new target gene for Parkinson’s disease treatment, garnering attention from the scientific community.
The findings, with Professor Choi as the lead author, were published in the prestigious journal Science Advances on April 11. The paper is titled Astrocytic RNA Editing Regulates the Host Immune Response to Alpha-Synuclein.