Discovery and Preclinical Validation of a Clinically Optimized Mitochondrial Complex I Modulator for Alzheimer’s Disease
safety margin. Importantly, C273 activated these mechanisms and reduced Aβ and p-Tau levels in induced pluripotent stem cell-derived cerebral organoids from patients with sporadic AD. Collectively, these results establish controlled mtCI modulation as a therapeutic strategy and position C273 as a promising disease-modifying candidate for AD.
Authors
- Alexander Galkin (ORCID: https://orcid.org/0000-0001-8469-2283)
- Eugenia Trushina (ORCID: https://orcid.org/0000-0002-6291-2860)
- Takahisa Kanekiyo (ORCID: https://orcid.org/0000-0001-6751-9374)
- Toshihiko Nambara (ORCID: https://orcid.org/0009-0001-3107-0680)
- Mark Ostroot (ORCID: https://orcid.org/0009-0009-1253-2120)
- Sergey Trushin (ORCID: https://orcid.org/0000-0003-0470-6345)
- Thi Kim Oanh Nguyen (ORCID: https://orcid.org/0000-0002-6068-6222)
- Wenyan Lu (ORCID: https://orcid.org/0009-0007-9803-5162)
- Graham Johnson
Institutions
- Mayo Clinic (US)
- Cornell University (US)
- MIND Research Institute (US)
- Nvidia (United States) (US)
- Mayo Clinic in Florida (US)
- Weill Cornell Medicine (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-14
- DOI
- https://doi.org/10.64898/2026.04.10.717554
- Primary Topic
- Metabolism, Diabetes, and Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00