New Insights into Parkinson's Disease: The Role of Inflammatory RNA Editing Enzyme ADAR1

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the abnormal accumulation of α-synuclein proteins within brain cells, leading to neuronal damage and motor dysfunction. Recent research conducted by researchers at KAIST has unveiled a novel mechanism involving RNA editing that contributes to neuroinflammation, a critical factor in the progression of PD.

Published in Science Advances, the study highlights the significance of the RNA-editing enzyme ADAR1 in modulating immune responses in glial cells, particularly astrocytes, which play a protective yet potentially damaging role in the brain's immune environment. The research team, led by Professor Minee L. Choi, collaborated with UCL and the Francis Crick Institute to investigate how inflammatory processes are regulated at the genetic level within brain immune cells.

Using a co-culture model derived from stem cells obtained from Parkinson's patients, the team treated these models with α-synuclein aggregates, known to trigger PD. They observed that early forms of α-synuclein, called oligomers, activate the Toll-like receptor pathway and interferon response pathway in astrocytes. During this activation, ADAR1 was upregulated, producing an isoform with altered structure and function.

A key finding was that the RNA editing activity of ADAR1, which normally serves to regulate immune responses during viral infections by converting adenosine to inosine (A-to-I editing), becomes abnormally focused on genes that promote inflammation. This aberrant activity was confirmed in postmortem brain tissues from PD patients, indicating its pathological relevance.

The dysregulation of RNA editing leads to persistent inflammatory responses in astrocytes, ultimately causing neuronal toxicity and disease progression. This discovery introduces RNA editing regulation within astrocytes as a crucial mechanism in PD pathogenesis and presents ADAR1 as a promising target for therapeutic intervention.

Furthermore, the study utilized patient-specific iPSC-based models, reflecting actual pathological features of PD, enhancing the translational potential of these findings. Professor Choi emphasized that targeting inflammation via RNA editing pathways could represent a radically different therapeutic approach compared to current treatments.

This research paves the way for new RNA-based diagnostic and therapeutic strategies for neuroinflammatory conditions like Parkinson's disease, emphasizing the importance of understanding molecular regulation at the genetic level. For more details, refer to the full study in Science Advances: [DOI: 10.1126/sciadv.adp8504].

source: https://medicalxpress.com/news/2025-05-parkinson-disease-discovery-inflammatory-rna.html