Parkinson’s disease (PD) is a neurodegenerative disorder in which the α-synuclein protein abnormally fads in brain cells, causing neural damage. Thanks to an international collaboration, Kaist researchers have revealed that RNA edition plays a crucial role in the regulation of neuroinflammation, a key pathology of Parkinson’s disease.
KAIST (represented by President Kwang-Hyung Lee) announced on April 27 that a research team led by Professor Minee L. Choi of the Brain Sciences and Cognitive Sciences Department, discovered that the ENzyme editing RNA ada the brain, and has shown that this mechanism is critically involved in the progress of Parkinson’s disease.
Professor Choi’s research team has created a co-culture model made up of astrocytes and neurons derived from stem cells from patients with Parkinson’s disease, in order to study the inflammatory responses of brain immune cells. They then dealt with the model with α-synuclein aggregates, which are known to cause Parkinson’s disease and analyzed how the inflammatory responses of immune cells have changed.
Consequently, it has been found that the first pathological forms of α-synuclein, called oligomers, activated the path of toll-type receptors, which acts as a danger sensor in astrocytes, as well as the response to interferon, a network of immune signaling which fights viruses and pathogens. During this process, the ADAR1 RNA edition enzyme was expressed and transformed into isoform with a modified structure and function.
In particular, the ADAR1 RNA publishing activity, which normally works to regulate immune responses during viral infections by converting adenosine (a) into inosin (i) by a process called edition of RNA A to I, has proven to be abnormally focused on genes which cause inflammation rather than operating under normal conditions. This phenomenon was observed not only in the models of patients derived from the patient, but also in post-mortem brain tissues of patients with Parkinson’s disease.
This directly proves that the deregulation of RNA publishing induces chronic inflammatory responses in astrocytes, ultimately leading to neuronal toxicity and pathological progression.
This study is significant in that it has newly identified the regulation of RNA publishing within astrocytes as a key mechanism behind neuroinflammatory responses. In particular, this suggests that ADAR1 could serve as a new genetic target for the treatment of Parkinson’s disease.
-It should also be noted that the study reflected the actual pathological characteristics of patients using precision precision models based on multi -sided stem cells induced by the patient for brain diseases.
This study demonstrates that the inflammation regulator caused by the aggregation of proteins operates on the new RNA editing layer, offering a completely different therapeutic strategy of the existing approaches to the treatment of Parkinson’s disease. “She also stressed that RNA publishing technology could become an important point of revolution in the development of therapy for neuroinflammation. »»
Professor Minee L. Choi
This study was published in Science Advances on April 11, with Professor Choi listed as a co-author.
Paper title: edition of the Astrocyte RNA regulates the host’s immune response to alpha-synuclein, science Advances vol.11, number 15. (DOI: 10.1126 / SCIADV.ADP8504)
Main authors: Karishma d’A SA (UCL, Co-Prime Author), Minee L. Choi (Kaist, Co-Prime Author), Mina Ryten (UCL, corresponding author), Sonia Gandhi (Francis Crick Institute, University of Cambridge, corresponding author)
This research was supported by the brain research program and the excellent program of young researchers from the National Research Foundation of Korea, as well as the Cognitive Improvement Program Daekyo de Kaist.
