» Articles » PMID: 39789319

RNA Dysregulation in Neurodegenerative Diseases

Overview
Journal EMBO J
Date 2025 Jan 9
PMID 39789319
Authors
Affiliations
Soon will be listed here.
Abstract

Dysregulation of RNA processing has in recent years emerged as a significant contributor to neurodegeneration. The diverse mechanisms and molecular functions underlying RNA processing underscore the essential role of RNA regulation in maintaining neuronal health and function. RNA molecules are bound by RNA-binding proteins (RBPs), and interactions between RNAs and RBPs are commonly affected in neurodegeneration. In this review, we highlight recent progress in understanding dysregulated RNA-processing pathways and the causes of RBP dysfunction across various neurodegenerative diseases. We discuss both established and emerging mechanisms of RNA-mediated neuropathogenesis in this rapidly evolving field. Furthermore, we explore the development of potential RNA-targeting therapeutic approaches for the treatment of neurodegenerative diseases.

References
1.
Agra Almeida Quadros A, Li Z, Wang X, Ndayambaje I, Aryal S, Ramesh N . Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer's disease. Acta Neuropathol. 2024; 147(1):9. PMC: 10766724. DOI: 10.1007/s00401-023-02655-0. View

2.
Barmada S, Ju S, Arjun A, Batarse A, Archbold H, Peisach D . Amelioration of toxicity in neuronal models of amyotrophic lateral sclerosis by hUPF1. Proc Natl Acad Sci U S A. 2015; 112(25):7821-6. PMC: 4485101. DOI: 10.1073/pnas.1509744112. View

3.
Yin S, Lopez-Gonzalez R, Kunz R, Gangopadhyay J, Borufka C, Gygi S . Evidence that C9ORF72 Dipeptide Repeat Proteins Associate with U2 snRNP to Cause Mis-splicing in ALS/FTD Patients. Cell Rep. 2017; 19(11):2244-2256. PMC: 5653973. DOI: 10.1016/j.celrep.2017.05.056. View

4.
Onofrj M, Ghilardi M . MPTP induced parkinsonian syndrome: long term follow-up and neurophysiological study. Ital J Neurol Sci. 1990; 11(5):445-58. DOI: 10.1007/BF02336564. View

5.
Lourenco M, Clarke J, Frozza R, Bomfim T, Forny-Germano L, Batista A . TNF-α mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer's β-amyloid oligomers in mice and monkeys. Cell Metab. 2013; 18(6):831-43. DOI: 10.1016/j.cmet.2013.11.002. View