DNA damage may help explain a genetic form of ALS and frontotemporal dementia
A review of experimental studies links a specific genetic repeat expansion to disrupted DNA repair, but it does not establish a treatment benefit in people.
Based on the published abstract. The full paper may contain additional methods, results and limitations.
The 30-second takeaway
The review connects C9orf72 repeat expansions and their associated proteins with damage to DNA and its repair systems. This offers a possible explanation for disease processes in this genetic form of ALS and frontotemporal dementia. Improvements in lifespan and movement were reported in mouse models after targeting DNA damage responses; human treatment benefits remain unestablished.
The abstract summarizes experimental models and postmortem tissue, without study-level methods or effect estimates. Mouse lifespan and motor findings cannot establish whether targeting these pathways improves symptoms or survival in people.
What the review examined
Researchers asked how DNA damage fits into disease linked to the C9orf72 expansion. The included evidence covered laboratory cell systems, neurons and tissue collected after death, rather than a clinical treatment trial.
Where the damage may arise
The authors identified disrupted damage signaling, less efficient DNA repair, unusual RNA–DNA structures and mitochondrial dysfunction with oxidative stress. They also described DNA damage feeding further repeat expansion and activating another cellular signaling pathway.
The original publication
C9orf72-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review.
Almalki S, Salama M, Taylor MJ et al.
Front Mol Neurosci · 2025
- PubMed ID
- 41341655
- Record checked
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