Lisinopril activates BI1 to reprogram lipid metabolism and restore autophagy in ALS
-induced apoptosis in NSC34 cells. Concurrently, it regulated TGF-β1/mTOR-dependent autophagy, maintained NMJ integrity, and reshaped triglyceride/sphingolipid/glycerophospholipid metabolism to attenuate spinal cord pathology in ALS mice, promoting energy metabolism shift toward glucose oxidation. Additionally, lisinopril inhibited the TGF-β1/Smad2/3 pathway to alleviate muscle fibrosis, downregulate Acp5/FN expression, and reduce type I collagen deposition. In conclusion, this study provides evidence that pharmacological activation of BI1 by lisinopril suppresses TGF-β1, modulates lipid metabolism, and ameliorates ALS pathology, demonstrating promising therapeutic repurposing potential.
Authors
- Fuqiang Zhang (ORCID: https://orcid.org/0000-0002-2627-5876)
- Yiyang Sun (ORCID: https://orcid.org/0009-0007-0417-8534)
- Zhichao Ren
- Yuxiang Wang (ORCID: https://orcid.org/0000-0001-5471-8315)
- LINLIN ZENG
- Hanlan Yin
- Xueqi Fu
- Yan Zhang
- Wenfu Yan
Institutions
- Union Hospital (HK)
- Jilin University (CN)
- Ministry of Education (KN)
- Union Hospital (CN)
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry
Publication Details
- Journal
- Communications Biology
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1038/s42003-026-09930-2
- Primary Topic
- Amyotrophic Lateral Sclerosis Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- People's Government of Jilin Province
- Department of Science and Technology of Jilin Province
- National Key Research and Development Program of China