Tilorone mitigates the propagation of α-synucleinopathy in a midbrain-like organoid model
Tilorone inhibits the uptake of sPFF in both mouse primary neurons and human midbrain-like organoids. Tilorone also reduces the phosphorylation of endogenous α-syn induced by pathogenic α-syn fibrils and mitigates α-syn fibril-induced apoptosis in midbrain-like organoids. Proteomic profiling of fibril-treated organoids reveals substantial alterations in lipid homeostasis by α-syn fibrils, which are reversed by Tilorone treatment. Given its safety profile in clinics, Tilorone may be further developed as a therapeutic intervention to alleviate the propagation of synucleinopathy in PD patients.
Authors
- Yue Xu (ORCID: https://orcid.org/0000-0002-5160-6251)
- Wei Zheng (ORCID: https://orcid.org/0000-0003-1034-0757)
- Meng Liu (ORCID: https://orcid.org/0000-0003-3114-9003)
- Yihong Ye (ORCID: https://orcid.org/0000-0002-9512-7922)
- B. Malique Jones (ORCID: https://orcid.org/0000-0002-6614-9962)
- Wenwei Huang (ORCID: https://orcid.org/0000-0002-7756-6577)
- Qi Zhang (ORCID: https://orcid.org/0000-0002-2639-9158)
- Bing Li (ORCID: https://orcid.org/0000-0001-6909-4752)
- Juhyung Lee (ORCID: https://orcid.org/0000-0002-3638-1496)
Institutions
- National Institutes of Health (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- National Cancer Institute (US)
- National Center for Advancing Translational Sciences (US)
Publication Details
- Journal
- Journal of Translational Medicine
- Published
- 2024-09-02
- DOI
- https://doi.org/10.1186/s12967-024-05551-7
- Citations
- 4
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.48
Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Center for Advancing Translational Sciences