The breaking point where repeat expansion triggers neuronal collapse in Huntington’s disease
Somatic CAG expansion drives neuronal loss in Huntington's disease (HD), but how expansion results in pathogenesis has remained unclear. Handsaker et al.<sup>1</sup> use single-cell RNA and repeat length sequencing to reveal a phased model of expansion and toxicity, highlighting a critical tipping point beyond 150 CAG repeats where neuronal identity collapses and cells die.
Authors
- Sarah J. Tabrizi (ORCID: https://orcid.org/0000-0003-2716-2045)
- Michael Flower (ORCID: https://orcid.org/0000-0001-5568-6239)
Institutions
- UK Dementia Research Institute (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- University College London (GB)
Publication Details
- Journal
- Cell Genomics
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1016/j.xgen.2025.100816
- Citations
- 2
- Primary Topic
- Genetic Neurodegenerative Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- CHDI Foundation
- Wellcome Trust
- Alzheimer's Society
- UK Dementia Research Institute
- Medical Research Council