R-loops in neurodegeneration DOI Creative Commons
Chiara Beghè,

Helena Harpham,

Yasmine Barberic

et al.

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102345 - 102345

Published: April 8, 2025

Neurodegenerative diseases are associated with the progressive loss of neurons. R-loops non-canonical nucleic acid structures formed during transcription and composed an RNA/DNA hybrid a displaced single-stranded DNA. Whilst important regulators cellular processes, they also pathologies multiple disorders, including repeat expansion, motor neuron, inflammatory ageing diseases. In this review, we discuss how contribute to pathological mechanisms that underpin neurodegeneration. We highlight role in several hallmarks neurodegenerative RNA DNA defects, damage, protein aggregation, inflammation, mitochondrial dysfunction, neuronal cell death. potential as therapeutic targets for disorders.

Language: Английский

R-loop homeostasis in genome dynamics, gene expression and development DOI
Paula Aguilera, Andrés Aguilera

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102325 - 102325

Published: March 4, 2025

Language: Английский

Citations

1
Oxidative stress and the multifaceted roles of ATM in maintaining cellular redox homeostasis DOI Creative Commons
Ji‐Hoon Lee

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103269 - 103269

Published: July 16, 2024

The ataxia telangiectasia mutated (ATM) protein kinase is best known as a master regulator of the DNA damage response. However, accumulating evidence has unveiled an equally vital function for ATM in sensing oxidative stress and orchestrating cellular antioxidant defenses to maintain redox homeostasis. can be activated through non-canonical pathway involving intermolecular disulfide crosslinking dimers, distinct from its canonical activation by double-strand breaks. Structural studies have elucidated conformational changes that allow switch into active redox-sensing state upon oxidation. Notably, loss results elevated reactive oxygen species (ROS) levels, altered profiles, mitochondrial dysfunction across multiple cell types tissues. This arising deficiency been implicated central driver neurodegenerative phenotypes ataxia-telangiectasia (A-T) patients, potentially mechanisms damage, PARP hyperactivation, widespread aggregation. Moreover, defective oxidation disrupts transcriptional programs RNA metabolism, with detrimental impacts on neuronal Significantly, therapy ameliorate organismal abnormalities various ATM-deficient models. review synthesizes recent advances illuminating multifaceted roles preserving balance mitigating insults, providing unifying paradigm understanding complex pathogenesis A-T disease.

Language: Английский

Citations

9
A-T neurodegeneration and DNA damage-induced transcriptional stress DOI
Tanya T. Paull, Phillip R. Woolley

DNA repair, Journal Year: 2024, Volume and Issue: 135, P. 103647 - 103647

Published: Feb. 15, 2024

Language: Английский

Citations

7
R-loops in neurodegeneration DOI Creative Commons
Chiara Beghè,

Helena Harpham,

Yasmine Barberic

et al.

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102345 - 102345

Published: April 8, 2025

Neurodegenerative diseases are associated with the progressive loss of neurons. R-loops non-canonical nucleic acid structures formed during transcription and composed an RNA/DNA hybrid a displaced single-stranded DNA. Whilst important regulators cellular processes, they also pathologies multiple disorders, including repeat expansion, motor neuron, inflammatory ageing diseases. In this review, we discuss how contribute to pathological mechanisms that underpin neurodegeneration. We highlight role in several hallmarks neurodegenerative RNA DNA defects, damage, protein aggregation, inflammation, mitochondrial dysfunction, neuronal cell death. potential as therapeutic targets for disorders.

Language: Английский

Citations

0