Researchers discover critical aberrations in the treatment of RNA

A study by a scientist at the Barrow Neurological Center on the mechanisms of treating dysfunctional RNA in ALS and frontaltemporal dementia (FTD) was published in the April issue of Acta Neuropathologica. The research was conducted by Dr. Rita Sattler and her graduate student Stephen Moore in her laboratory at the Department of Neurobiology at the Barrow Neurological Institute, which is dedicated to understanding the mechanisms of the disease in ALS, FTD, and related neurodegenerative diseases. .

The research presented reveals that a protein specific to RNA treatment, called ADAR2, undergoes a poor cellular localization and is located in an unexpected region of neurons in the brain tissue of ALT / FTD patient post-mortem. This altered cell localization leads to dysfunctional RNA alterations, which have an impact on the major pathways of the disease involved in neurodegeneration in the most common subgroup of ALS / FTD patients, those characterized by mutation. of the C9orf72 gene. These dysfunctions are likely to contribute to neuronal loss in other neurodegenerative diseases and could potentially be saved by therapeutic intervention with compounds that prevent the poor cellular localization of ADAR2.

"These results underscore the importance of RNA treatment in ALS and FTD and suggest that treatments targeting the erroneous localization of these RNA binding proteins could be beneficial to patients." neurodegenerative diseases, "says Dr. Rita Sattler, badociate professor of neurobiology and neurology in Barrow.

The research was conducted in Barrow, which is part of the Dignity Health St. Joseph Hospital and Medical Center, in close collaboration with TGen and other institutions across the country. Dr. Sattler and her team have yielded their results by examining the cellular localization of ADAR2 in various disease models, followed by a transcriptome badysis of tissues and iPSCs using sequencing technology. RNA. Data were badyzed to determine changes in RNA treatment and compared to data obtained in healthy control volunteers.

The research was funded by the Barrow Neurological Foundation, the National Institute of Health, the ALS Association, the Muscle Dystrophy Association, and the Robert Packard Center for ALS Research at Johns Hopkins University.

The ultimate goal of this research is to test new compounds that will prevent ADAR2 from altering its cellular location and hence avoid RNA editing aberrations and improve health. neuronal.

Future research aims to examine the individual genes of the cellular pathways affected by the mis-localization of ADAR2 and the aberrant RNA editing. This could lead to the discovery of new, more specific therapeutic targets for patients with neurodegenerative diseases.