1371-TOP1-Mediated Genomic Damage in ALS

Paper Talk · Aug 2, 2026 · 14m

This study utilizes single-cell whole-genome sequencing to reveal that neurons in ALS, FTD, and Alzheimer’s disease exhibit significantly elevated levels of somatic mutations compared to healthy brains. Researchers identified a specific mutational signature primarily composed of 2-bp deletions, which serves as a unifying marker of genomic instability across these diverse neurodegenerative conditions. This damage is driven by the aberrant activity of topoisomerase 1 (TOP1), an enzyme that becomes trapped on DNA and causes strand breaks, especially under conditions of oxidative stress…