Mapping the Future of Oxidative RNA Damage in Neurodegeneration: Rethinking the Status Quo with New Tools

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2024 Nov 4

PMID 39495912

Authors

Hailey B Wheeler

Assael A Madrigal

Isaac A Chaim

Affiliations

Soon will be listed here.

Abstract

Over two decades ago, increased levels of RNA oxidation were reported in postmortem patients with ALS, Alzheimer's, Parkinson's, and other neurodegenerative diseases. Interestingly, not all cell types and transcripts were equally oxidized. Furthermore, it was shown that RNA oxidation is an early phenomenon, altogether indicating that oxidative RNA damage could be a driver, and not a consequence, of disease. Despite all these exciting observations, the field appears to have stagnated since then. We argue that this is a consequence of the shortcomings of technologies to model these diseases, limiting our understanding of which transcripts are being oxidized, which RNA-binding proteins are interacting with these RNAs, what their implications are in RNA processing, and as a result, what their potential role is in disease onset and progression. Here, we discuss the limits of previous technologies and propose ways by which advancements in iPSC-derived disease modeling, proteomics, and sequencing technologies can be combined and leveraged to answer new and decades-old questions.

Citing Articles

RNA dynamics in oxidative stress: From obscurity to mechanistic understanding in health and disease.

Contreras L, Belfort M Proc Natl Acad Sci U S A. 2024; 121(46):e2420445121.

PMID: 39495921 PMC: 11573495. DOI: 10.1073/pnas.2420445121.

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