Simultaneous inhibition of mTOR and STING as an approach to reduce alpha-synuclein and lysosphingolipid levels in peripheral blood monocytederived macrophages and the SH-SY5Y cell line: implications for therapy of Parkinson’s disease
Abstract
The combined effects of two inhibitors, Torin 1, acting on mTOR, a key regulator of autophagy, and H-151, inhibiting STING, a key regulator of inflammation, on the autophagolysosomal system, have been studied in a primary culture of peripheral blood macrophages from healthy donors and the SH-SY5Y neuroblastoma cell line. Combined use of these drugs resulted in a decrease in the levels of lysosphingolipids, triggering alpha-synuclein oligomerization, as well as a decrease in the levels of monomeric and neurotoxic phosphorylated (Ser129) alpha-synuclein and an increase in tyrosine hydroxylase. These results open new prospects for the use of combination therapy with these proposed drugs in the treatment of both diseases associated with lysosomal dysfunction and neurodegenerative pathologies.
Fields of Study & Subjects
interferon and immune responses
Autophagy in Disease and Therapy
Inflammasome and immune disorders
Publication details
- Journal / source
- Biomeditsinskaya Khimiya
- Publisher
- Institute of Biochemistry
- Volume
- 72
- Issue
- 1
- Pages
- 42–61
- Publication date
- 1 January 2026
- Language
- RU