Schematic diagram of the inflammatory RNA modifying mannequin in Parkinson’s illness. Credit score: Science Advances (2025). DOI: 10.1126/sciadv.adp8504
Parkinson’s illness (PD) is a neurodegenerative dysfunction by which the α-synuclein protein abnormally aggregates inside mind cells, inflicting neuronal injury. By way of worldwide collaboration, researchers at KAIST have revealed that RNA modifying performs a vital function in regulating neuroinflammation, a key pathology of Parkinson’s illness.
The paper is printed within the journal Science Advances.
The analysis crew, led by Professor Minee L. Choi from the Division of Mind and Cognitive Sciences, in collaboration with College School London (UCL) and the Francis Crick Institute, found that the RNA-editing enzyme ADAR1 performs an essential function in controlling immune responses in astrocytes, glial cells that set off protecting reactions within the mind, and demonstrated that this mechanism is critically concerned within the development of Parkinson’s illness.
Professor Choi’s analysis crew created a co-culture mannequin composed of astrocytes and neurons derived from stem cells originating from Parkinson’s illness sufferers, with a purpose to research the inflammatory responses of mind immune cells. They then handled the mannequin with α-synuclein aggregates, that are recognized to trigger Parkinson’s illness, and analyzed how the immune cells’ inflammatory responses modified.
They discovered that early pathological types of α-synuclein, often known as oligomers, activated the Toll-like receptor pathway, which acts as a hazard sensor in astrocytes, in addition to the interferon response pathway, an immune signaling community that combats viruses and pathogens. Throughout this course of, the RNA modifying enzyme ADAR1 was expressed and remodeled into an isoform with an altered protein construction and performance.
Experimental design and inflammatory response induction in astrocytes following therapy with α-synuclein oligomers (abnormally folded protein fragments). Credit score: Science Advances (2025). DOI: 10.1126/sciadv.adp8504
Notably, the RNA modifying exercise of ADAR1, which usually features to control immune responses throughout viral infections by changing adenosine (A) to inosine (I) by way of a course of often known as A-to-I RNA modifying, was discovered to be abnormally targeted on genes that trigger irritation quite than working underneath regular situations. This phenomenon was noticed not solely within the patient-derived neuron fashions but additionally in postmortem mind tissues from precise Parkinson’s illness sufferers.
This straight proves that the dysregulation of RNA modifying induces continual inflammatory responses in astrocytes, in the end resulting in neuronal toxicity and pathological development.
This research is important in that it newly recognized the regulation of RNA modifying inside astrocytes as a key mechanism behind neuroinflammatory responses. Particularly, it means that ADAR1 might function a novel genetic goal for the therapy of Parkinson’s illness.
When handled with α-synuclein oligomers, the causative agent of Parkinson’s illness, A-to-I RNA modifying is induced to alter genetic data by ADAR in patient-derived stem cell-differentiated glial cells, confirming that α-synuclein is more likely to be related to the development of Parkinson’s illness by way of RNA modifying. Credit score: Science Advances (2025). DOI: 10.1126/sciadv.adp8504
It’s also noteworthy that the research mirrored precise pathological traits of sufferers by using patient-specific induced pluripotent stem cell-based precision fashions for mind illnesses.
Professor Minee L. Choi said, “This study demonstrates that the regulator of inflammation caused by protein aggregation operates at the new layer of RNA editing, offering a completely different therapeutic strategy from existing approaches to Parkinson’s disease treatment.”
She additional emphasised, “RNA editing technology could become an important turning point in the development of therapeutics for neuroinflammation.”
Extra data:
Karishma D’Sa et al, Astrocytic RNA modifying regulates the host immune response to alpha-synuclein, Science Advances (2025). DOI: 10.1126/sciadv.adp8504
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The Korea Superior Institute of Science and Know-how (KAIST)
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Enhancing Parkinson’s illness—discovery of an inflammatory RNA modifying enzyme (2025, Could 2)
retrieved 3 Could 2025
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