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
1. Petersburg Nuclear Physics Institute named by B.P. Konstantinov of NRC “Kurchatov Institute”, Gatchina, Leningrad region, Russia; First Pavlov State Medical University of St. Petersburg, Saint Petersburg, Russia 2. Petersburg Nuclear Physics Institute named by B.P. Konstantinov of NRC “Kurchatov Institute”, Gatchina, Leningrad region, Russia 3. Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Saint Petersburg, Russia 4. Medical Genetic Research Center, Moscow, Russia
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.
Bezrukova A.I., Basharova K.S., Galkina E.S., Epifanivskaya O.S., Baydakova G.V., Zakharova E.Yu., Pchelina S.N., Usenko T.S. (2026) 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. Biomeditsinskaya Khimiya, 72(1), 42-61.
Bezrukova A.I. et al. 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 // Biomeditsinskaya Khimiya. - 2026. - V. 72. -N 1. - P. 42-61.
Bezrukova A.I. et al., "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." Biomeditsinskaya Khimiya 72.1 (2026): 42-61.
Bezrukova, A. I., Basharova, K. S., Galkina, E. S., Epifanivskaya, O. S., Baydakova, G. V., Zakharova, E. Yu., Pchelina, S. N., Usenko, T. S. (2026). 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. Biomeditsinskaya Khimiya, 72(1), 42-61.
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