Allyl-substituted ALT001 promotes alternative mitophagy and improves therapeutic outcomes in Alzheimer’s disease models
for inducing mitophagy, while maintaining low cytotoxicity, and it exerted this effect via the alternative mitophagy pathway. Similarly, ALT001-4a induced mitophagy in the hippocampus of mice at a fourfold lower dose than ALT001. Importantly, ALT001-4a successfully restored mitochondrial and cognitive function in both a cellular AD model and a 5xFAD AD model. These findings suggest that the structural modification of ALT001 can generate derivatives with superior potency and potential for treating Alzheimer's disease and that further optimization could enable the development of ALT001-4a as a viable therapeutic agent for AD.
Authors
- Young Yeon Kim
- Se Myeong Choi (ORCID: https://orcid.org/0000-0003-0431-9185)
- Jeanho Yun (ORCID: https://orcid.org/0000-0001-7700-5123)
- Jong Hyun Cho (ORCID: https://orcid.org/0000-0002-0995-6952)
- Han‐Joo Maeng (ORCID: https://orcid.org/0000-0003-1441-7301)
- Dong Jin Shin (ORCID: https://orcid.org/0000-0003-4346-4000)
- Eunhee Yoo
- Alen Benhur Pravin Nathan
- Jihoon Jo
- Jee-Hyun Um
Institutions
- Chonnam National University (KR)
- Gachon University (KR)
- Altair Engineering (United States) (US)
- Chonnam National University Hospital (KR)
- Dong-A University (KR)
Publication Details
- Journal
- Scientific Reports
- Published
- 2026-04-17
- DOI
- https://doi.org/10.1038/s41598-026-48974-6
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Research Foundation
- Korea Basic Science Institute
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea