Metformin improves RAN protein pathology, alternative splicing, and behavioral phenotypes in SCA8 mice - PubMed
4 hours ago
- #Metformin
- #RAN translation
- #SCA8
- Metformin improves RAN protein pathology, alternative splicing, and behavioral phenotypes in SCA8 mice.
- SCA8 is a neurological disease caused by CAG•CTG expansions, with no effective treatments currently available.
- RAN translation occurs across CAG and CUG expansion transcripts, making SCA8 treatments relevant to other diseases like Huntington's and myotonic dystrophy.
- Metformin-treated SCA8 mice showed improved ambulatory performance in rotarod, DigiGait, and open-field tests.
- Molecular improvements included reduced RAN protein levels and better splicing, without altering RNA levels.
- Metformin also decreased neuroinflammation, reducing astrogliosis and activated microglia.
- Findings support clinical trials for metformin in SCA8 and other CAG•CTG repeat expansion disorders.