{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:25:35Z","timestamp":1778153135165,"version":"3.51.4"},"reference-count":88,"publisher":"Institute of Biochemistry","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BIOMED KHIM"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.18097\/pbmcr1616","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T17:51:32Z","timestamp":1772646692000},"page":"42-61","source":"Crossref","is-referenced-by-count":1,"title":["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\u2019s disease"],"prefix":"10.18097","volume":"72","author":[{"given":"A.I.","family":"Bezrukova","sequence":"first","affiliation":[{"name":"Petersburg Nuclear Physics Institute named by B.P. Konstantinov of NRC \u201cKurchatov Institute\u201d, Gatchina, Leningrad region, Russia; First Pavlov State Medical University of St. Petersburg, Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.S.","family":"Basharova","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute named by B.P. Konstantinov of NRC \u201cKurchatov Institute\u201d, Gatchina, Leningrad region, Russia; First Pavlov State Medical University of St. Petersburg, Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.S.","family":"Galkina","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute named by B.P. Konstantinov of NRC \u201cKurchatov Institute\u201d, Gatchina, Leningrad region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.S.","family":"Epifanivskaya","sequence":"additional","affiliation":[{"name":"Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.V.","family":"Baydakova","sequence":"additional","affiliation":[{"name":"Medical Genetic Research Center, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.Yu.","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Medical Genetic Research Center, Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.N.","family":"Pchelina","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute named by B.P. Konstantinov of NRC \u201cKurchatov Institute\u201d, Gatchina, Leningrad region, Russia; First Pavlov State Medical University of St. Petersburg, Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.S.","family":"Usenko","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute named by B.P. Konstantinov of NRC \u201cKurchatov Institute\u201d, Gatchina, Leningrad region, Russia; First Pavlov State Medical University of St. Petersburg, Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7443","published-online":{"date-parts":[[2026]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Funayama M., Nishioka K., Li Y., Hattori N. (2023) Molecular genetics of Parkinson\u2019s disease: contributions and global trends. J. Hum. Genet., 68(3), 125\u2013130.","DOI":"10.1038\/s10038-022-01058-5"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Schneider S.A., Alcalay R.N. (2020) Precision medicine in Parkinson\u2019s disease: emerging treatments for genetic Parkinson\u2019s disease. J. Neurol., 267(3), 860\u2013869.","DOI":"10.1007\/s00415-020-09705-7"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Schneider S.A., Alcalay R.N. (2017) Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Mov. Disord., 32(11), 1504\u20131523.","DOI":"10.1002\/mds.27193"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Dorsey E.R., Bloem B.R. (2018) The Parkinson pandemic \u2014 a call to action. JAMA Neurol., 75(1), 9\u201310.","DOI":"10.1001\/jamaneurol.2017.3299"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Calabresi P., Mechelli A., Natale G., Volpicelli-Daley L., di Lazzaro G., Ghiglieri V. (2023) Alpha-synuclein in Parkinson\u2019s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell Death Dis., 14(3), 176.","DOI":"10.1038\/s41419-023-05672-9"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Lu J., Wu M., Yue Z. (2020) Autophagy and Parkinson\u2019s disease. Adv. Exp. Med. Biol., 1207, 21\u201351.","DOI":"10.1007\/978-981-15-4272-5_2"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Tansey M.G., Wallings R.L., Houser M.C., Herrick M.K., Keating C.E., Joers V. (2022) Inflammation and immune dysfunction in Parkinson disease. Nat. Rev. Immunol., 22(11), 657\u2013673.","DOI":"10.1038\/s41577-022-00684-6"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Pajares M., Rojo A.I., Manda G., Bosc\u00e1 L., Cuadrado A. (2020) Inflammation in Parkinson\u2019s disease: mechanisms and therapeutic implications. Cells, 9(7), 1687.","DOI":"10.3390\/cells9071687"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Bezrukova A.I., Basharova K.S., Emelyanov A.K., Rybakov A.V., Miliukhina I.V., Pchelina S.N., Usenko T.S. (2025) Autophagy process in Parkinson\u2019s disease depends on mutations in the GBA1 and LRRK2 genes. Biochem. Genet., DOI: 10.1007\/s10528-025-11125-z.","DOI":"10.1007\/s10528-025-11125-z"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Minchev D., Kazakova M., Sarafian V. (2022) Neuroinflammation and autophagy in Parkinson\u2019s disease \u2014 novel perspectives. Int. J. Mol. Sci., 23(23), 14997.","DOI":"10.3390\/ijms232314997"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Zhang W., Xiao D., Mao Q., Xia H. (2023) Role of neuroinflammation in neurodegeneration development. Signal Transduct. Target. Ther., 8, 267.","DOI":"10.1038\/s41392-023-01486-5"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Moors T., Paciotti S., Chiasserini D., Calabresi P., Parnetti L., Beccari T., van de Berg W.D.J. (2016) Lysosomal dysfunction and \u03b1-synuclein aggregation in Parkinson\u2019s disease: diagnostic links. Mov. Disord., 31(6), 791\u2013801.","DOI":"10.1002\/mds.26562"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Pupyshev A.B., Tenditnik M.V., Ovsyukova M.V., Akopyan A.A., Dubrovina N.I., Tikhonova M.A. (2021) Restoration of Parkinson\u2019s disease-like deficits by activating autophagy through mTOR-dependent and mTOR-independent mechanisms in pharmacological and transgenic models of Parkinson\u2019s disease in mice. Bull. Exp. Biol. Med., 171(4), 425\u2013430.","DOI":"10.47056\/0365-9615-2021-171-4-429-435"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Khan M.R., Yin X., Kang S.-U., Mitra J., Wang H., Ryu T., Brahmachari S., Karuppagounder S.S., Kimura Y., Jhaldiyal A., Kim H.H., Gu H., Chen R., Redding-Ochoa J., Troncoso J., Na C.H., Ha T., Dawson V.L., Dawson T.M. (2024) Enhanced mTORC1 signaling and protein synthesis in pathologic \u03b1-synuclein cellular and animal models of Parkinson\u2019s disease. Sci. Transl. Med., 15(724), eadd0499.","DOI":"10.1126\/scitranslmed.add0499"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Xu J., Ao Y.-L., Huang C., Song X., Zhang G., Cui W., Wang Y., Zhang X.-Q., Zhang Z. (2022) Harmol promotes \u03b1-synuclein degradation and improves motor impairment in Parkinson\u2019s models via regulating autophagy-lysosome pathway. NPJ Parkinsons Dis., 8, 100.","DOI":"10.1038\/s41531-022-00361-4"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Ge Y., Huang M., Yao Y.-M. (2018) Autophagy and proinflammatory cytokines: interactions and clinical implications. Cytokine Growth Factor Rev., 43, 38\u201346.","DOI":"10.1016\/j.cytogfr.2018.07.001"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Usenko T.S., Nikolaev M.A., Miliukhina I.V., Bezrukova A.I., Senkevich K.A., Gomzyakova N.A., Beltceva Y.A., Zalutskaya N.M., Gracheva E.V., Timofeeva A.A., Petrova O.A., Semenov A.V., Lubimova N.E., Totolyan A.A., Pchelina S.N. (2020) Plasma cytokine profile in synucleinophaties with dementia. J. Clin. Neurosci., 78, 323\u2013326.","DOI":"10.1016\/j.jocn.2020.04.058"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Miliukhina I.V., Usenko T.S., Senkevich K.A., Nikolaev M.A., Timofeeva A.A., Agapova E.A., Semenov A.V., Lubimova N.E., Totolyan A.A., Pchelina S.N. (2020) Plasma cytokines profile in patients with Parkinson\u2019s disease associated with mutations in GBA gene. Bull. Exp. Biol. Med., 168(4), 423\u2013426.","DOI":"10.1007\/s10517-020-04723-x"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Bu X.-L., Wang X., Xiang Y., Shen L.-L., Wang Q.-H., Liu Y.-H., Jiao S.-S., Wang Y.-R., Cao H.-Y., Yi X., Liu C.-H., Deng B., Yao X.-Q., Xu Z.-Q., Zhou H.-D., Wang Y.-J. (2015) The association between infectious burden and Parkinson\u2019s disease: a case-control study. Parkinsonism Relat. Disord., 21(8), 877\u2013881.","DOI":"10.1016\/j.parkreldis.2015.05.015"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Usenko T., Bezrukova A., Basharova K., Panteleeva A., Nikolaev M., Kopytova A., Miliukhina I., Emelyanov A., Zakharova E., Pchelina S. (2021) Comparative transcriptome analysis in monocyte-derived macrophages of asymptomatic GBA mutation carriers and patients with GBA-associated Parkinson\u2019s disease. Genes, 12(10), 1545.","DOI":"10.3390\/genes12101545"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Mubariz F., Saadin A., Lingenfelter N., Sarkar C., Banerjee A., Lipinski M.M., Awad O. (2023) Deregulation of mTORC1-TFEB axis in human iPSC model of GBA1-associated Parkinson\u2019s disease. Front. Neurosci., 17, 1152503.","DOI":"10.3389\/fnins.2023.1152503"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Bogetofte H., Ryan B.J., Jensen P., Schmidt S.I., Vergoossen D.L.E., Barnkob M.B., Kiani L.N., Chughtai U., Heon-Roberts R., Caiazza M.C., McGuinness W., M\u00e1rquez-G\u00f3mez R., Vowles J., Bunn F.S., Brandes J., Kilfeather P., Connor J.P., Fernandes H.J.R., Caffrey T.M., Meyer M., Cowley S.A., Larsen M.R., Wade-Martins R. (2023) Post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson\u2019s disease GBA-N370S dopamine neurons. Cell Rep., 42(3), 112180.","DOI":"10.1016\/j.celrep.2023.112180"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Chen S., Saeed A.F.U.H., Liu Q., Jiang Q., Xu H., Xiao G.G., Rao L., Duo Y. (2023) Macrophages in immunoregulation and therapeutics. Signal Transduct. Target. Ther., 8, 207.","DOI":"10.1038\/s41392-023-01452-1"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Xicoy H., Wieringa B., Martens G.J.M. (2017) The SH-SY5Y cell line in Parkinson\u2019s disease research: a systematic review. Mol. Neurodegener., 12, 10.","DOI":"10.1186\/s13024-017-0149-0"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Kopytova A.E., Rychkov G.N., Nikolaev M.A., Baydakova G.V., Cheblokov A.A., Senkevich K.A., Bogdanova D.A., Bolshakova O.I., Miliukhina I.V., Bezrukikh V.A., Salogub G.N., Sarantseva S.V., Usenko T.C., Zakharova E.Y., Emelyanov A.K., Pchelina S.N. (2021) Ambroxol increases glucocerebrosidase (GCase) activity and restores GCase translocation in primary patient-derived macrophages in Gaucher disease and parkinsonism. Parkinsonism Relat. Disord., 84, 112\u2013121.","DOI":"10.1016\/j.parkreldis.2021.02.003"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Usenko T.S., Basharova K.S., Bezrukova A.I., Nikolaev M.A., Miliukhina I.V., Baydakova G.V., Zakharova E.Y., Pchelina S.N. (2022) Selective inhibition of LRRK2 activity as an approach to the treatment of Parkinson's disease. Medical Genetics, 21(12), 26\u201329.","DOI":"10.25557\/2073-7998.2022.12.26-29"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Kopytova A.E., Rychkov G.N., Cheblokov A.A., Grigor\u2019eva E.V., Nikolaev M.A., Yarkova E.S., Sorogina D.A., Ibatullin F.M., Baydakova G.V., Izyumchenko A.D., Bogdanova D.A., Boitsov V.M., Rybakov A.V., Miliukhina I.V., Bezrukikh V.A., Salogub G.N., Zakharova E.Y., Pchelina S.N., Emelyanov A.K. (2023) Potential binding sites of pharmacological chaperone NCGC00241607 on mutant \u03b2-glucocerebrosidase and its efficacy on patient-derived cell cultures in Gaucher and Parkinsons disease. Int. J. Mol. Sci., 24(10), 9105.","DOI":"10.3390\/ijms24109105"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Mart\u00ednez M.-A., Rodr\u00edguez J.-L., Lopez-Torres B., Mart\u00ednez M., Mart\u00ednez-Larra\u00f1aga M.-R., Maximiliano J.-E., Anad\u00f3n A., Ares I. (2020) Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ. Int., 135, 105414.","DOI":"10.1016\/j.envint.2019.105414"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"Usenko T.S., Timofeeva A., Beletskaia M., Basharova K., Baydakova G., Bezrukova A., Grunina M., Emelyanov A., Miliukhina I., Zakharova E., Pchelina S. (2024) The effect of p.G2019S mutation in the LRRK2 gene on the activity of lysosomal hydrolases and the clinical features of Parkinson\u2019s disease associated with p.N370S mutation in the GBA1 gene. J. Integr. Neurosci., 23(1), 16.","DOI":"10.31083\/j.jin2301016"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Usenko T.S., Senkevich K.A., Basharova K.S., Bezrukova A.I., Baydakova G.V., Tyurin A.A., Beletskaya M.V., Kulabukhova D.G., Grunina M.N., Emelyanov A.K., Miliukhina I.V., Timofeeva A.A., Zakharova E.Y., Pchelina S.N. (2023) LRRK2 exonic variants are associated with lysosomal hydrolase activities and lysosphingolipid alterations in Parkinson\u2019s disease. Gene, 882, 147639.","DOI":"10.1016\/j.gene.2023.147639"},{"key":"ref31","unstructured":"R Core Team (2025) R: a language and environment for statistical computing. R foundation for statistical computing, Vienna, Austria. https:\/\/www.R-project.org\/."},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Bezrukova A.I., Basharova K.S., Baydakova G.V., Zakharova E.Y., Pchelina S.N., Usenko T.S. (2024) Dose-dependent alterations of lysosomal activity and alpha-synuclein in peripheral blood monocyte-derived macrophages and SH-SY5Y neuroblastoma cell line by upon inhibition of mTOR protein kinase \u2014 assessment of the prospects of Parkinson\u2019s disease therapy. Biochemistry (Moscow), 89(7), 1300\u20131312.","DOI":"10.31857\/S0320972524070085"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"Kulkarni A., Dong A., Kulkarni V.V., Chen J., Laxton O., Anand A., Maday S. (2020) Differential regulation of autophagy during metabolic stress in astrocytes and neurons. Autophagy 16(9), 1651\u20131667.","DOI":"10.1080\/15548627.2019.1703354"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Arotcarena M.-L., Teil M., Dehay B. (2019) Autophagy in synucleinopathy: the overwhelmed and defective machinery. Cells, 8(6), 565.","DOI":"10.3390\/cells8060565"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Lin K.-J., Lin K.-L., Chen S.-D., Liou C.-W., Chuang Y.-C., Lin H.-Y., Lin T.-K. (2019) The overcrowded crossroads: mitochondria, alpha-synuclein, and the endo-lysosomal system interaction in Parkinson\u2019s disease. Int. J. Mol. Sci., 20(21), 5312.","DOI":"10.3390\/ijms20215312"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Dolgacheva L.P., Fedotova E.I., Abramov A.Y., Berezhnov A.V. (2018) Alpha-synuclein and mitochondrial dysfunction in Parkinson\u2019s disease. Biochemistry (Moscow) Suppl. Ser.A Membr. Cell. Biol., 12, 10\u201319.","DOI":"10.7868\/S0233475517050012"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Sep\u00falveda D., Cisternas-Olmedo M., Arcos J., Nassif M., Vidal R.L. (2022) Contribution of autophagy-lysosomal pathway in the exosomal secretion of alpha-synuclein and its impact in the progression of Parkinson\u2019s disease. Front. Mol. Neurosci., 15, 805087.","DOI":"10.3389\/fnmol.2022.805087"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Brown R.A., Voit A., Srikanth M.P., Thayer J.A., Kingsbury T.J., Jacobson M.A., Lipinski M.M., Feldman R.A., Awad O. (2019) mTOR hyperactivity mediates lysosomal dysfunction in Gaucher\u2019s disease iPSC-neuronal cells. Dis. Model. Mech., 12(10), dmm038596.","DOI":"10.1242\/dmm.038596"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Zhuang X.-X., Wang S.-F., Tan Y., Song J.-X., Zhu Z., Wang Z.-Y., Wu M.-Y., Cai C.-Z., Huang Z.-J., Tan J.-Q., Su H.-X., Li M., Lu J.-H. (2020) Pharmacological enhancement of TFEB-mediated autophagy alleviated neuronal death in oxidative stress-induced Parkinson\u2019s disease models. Cell Death Dis., 11(2), 128.","DOI":"10.1038\/s41419-020-2322-6"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Jiang T.-F., Zhang Y.-J., Zhou H.-Y., Wang H.-M., Tian L.-P., Liu J., Ding J.-Q., Chen S.-D. (2013) Curcumin ameliorates the neurodegenerative pathology in A53T \u03b1-synuclein cell model of Parkinson\u2019s disease through the downregulation of mTOR\/p70S6K signaling and the recovery of macroautophagy. J. Neuroimmune Pharmacol., 8(1), 356\u2013369.","DOI":"10.1007\/s11481-012-9431-7"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Bov\u00e9 J., Mart\u00ednez-Vicente M., Vila M. (2011) Fighting neurodegeneration with rapamycin: mechanistic insights. Nat. Rev. Neurosci., 12(8), 437\u2013452.","DOI":"10.1038\/nrn3068"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Malagelada C., Jin Z.H., Jackson-Lewis V., Przedborski S., Greene L.A. (2010) Rapamycin protects against neuron death in in vitro and in vivo models of Parkinson\u2019s disease. J. Neurosci., 30(3), 1166\u20131175.","DOI":"10.1523\/JNEUROSCI.3944-09.2010"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Dehay B., Bov\u00e9 J., Rodr\u00edguez-Muela N., Perier C., Recasens A., Boya P., Vila M. (2010) Pathogenic lysosomal depletion in Parkinson\u2019s disease. J. Neurosci., 30(37), 12535\u201312544.","DOI":"10.1523\/JNEUROSCI.1920-10.2010"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Usenko T., Bezrukova A., Rudenok M.M., Basharova K., Shadrina M.I., Slominsky P.A., Zakharova E., Pchelina S. (2023) Whole transcriptome analysis of substantia nigra in mice with MPTP-induced parkinsonism bearing defective glucocerebrosidase activity. Int. J. Mol. Sci., 24(15), 12164.","DOI":"10.3390\/ijms241512164"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Hussain B., Xie Y., Jabeen U., Lu D., Yang B., Wu C., Shang G. (2022) Activation of STING based on its structural features. Front. Immunol., 13, 808607.","DOI":"10.3389\/fimmu.2022.808607"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Gui X., Yang H., Li T., Tan X., Shi P., Li M., Du F., Chen Z.J. (2019) Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature, 567(7747), 262\u2013266.","DOI":"10.1038\/s41586-019-1006-9"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Wang Y., Wang F., Zhang X. (2021) STING-associated vasculopathy with onset in infancy: a familial case series report and literature review. Ann. Transl. Med., 9(2), 176.","DOI":"10.21037\/atm-20-6198"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Hagiwara A.M., Moore R.E., Wallace D.J., Ishimori M., Jefferies C.A. (2021) Regulation of cGAS-STING pathway \u2014 implications for systemic lupus erythematosus. Rheumatol. Immunol. Res., 2(3), 173\u2013184.","DOI":"10.2478\/rir-2021-0023"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Hinkle J.T., Patel J., Panicker N., Karuppagounder S.S., Biswas D., Belingon B., Chen R., Brahmachari S., Pletnikova O., Troncoso J.C., Dawson V.L., Dawson T.M. (2022) STING mediates neurodegeneration and neuroinflammation in nigrostriatal \u03b1-synucleinopathy. Proc. Natl. Acad. Sci. USA, 119(15), e2118819119.","DOI":"10.1073\/pnas.2118819119"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Standaert D.G., Childers G.M. (2022) Alpha-synucleinmediated DNA damage, STING activation, and neuroinflammation in Parkinson\u2019s disease. Proc. Natl. Acad. Sci. USA, 119(17), e2204058119.","DOI":"10.1073\/pnas.2204058119"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"Huang Y., Liu B., Sinha S.C., Amin S., Gan L. (2023) Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders. Mol. Neurodegener., 18, 79.","DOI":"10.1186\/s13024-023-00672-x"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Wang R., Sun H., Cao Y., Zhang Z., Chen Y., Wang X., Liu L., Wu J., Xu H., Wu D., Mu C., Hao Z., Qin S., Ren H., Han J., Fang M., Wang G. (2024) Glucosylceramide accumulation in microglia triggers STING-dependent neuroinflammation and neurodegeneration in mice. Sci. Signal., 17(829), eadk8249.","DOI":"10.1126\/scisignal.adk8249"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Schmid M., Fischer P., Engl M., Widder J., Kerschbaum-Gruber S., Slade D. (2024) The interplay between autophagy and cGAS-STING signaling and its implications for cancer. Front. Immunol., 15, 1356369.","DOI":"10.3389\/fimmu.2024.1356369"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Zhang Z., Zhou H., Ouyang X., Dong Y., Sarapultsev A., Luo S., Hu D. (2022) Multifaceted functions of STING in human health and disease: from molecular mechanism to targeted strategy. Signal. Transduct. Target. Ther., 7, 394.","DOI":"10.1038\/s41392-022-01252-z"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Wang B., Wang Y., Qiu J., Gao S., Yu S., Sun D., Lou H. (2023) The STING inhibitor C-176 attenuates MPTP-induced neuroinflammation and neurodegeneration in mouse parkinsonian models. Int. Immunopharmacol., 124(Pt A), 110827.","DOI":"10.1016\/j.intimp.2023.110827"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Hu X., Zhang H., Zhang Q., Yao X., Ni W., Zhou K. (2022) Emerging role of STING signalling in CNS injury: inflammation, autophagy, necroptosis, ferroptosis and pyroptosis. J. Neuroinflammation, 19, 242.","DOI":"10.1186\/s12974-022-02602-y"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Cheng J., Liao Y., Dong Y., Hu H., Yang N., Kong X., Li S., Li X., Guo J., Qin L., Yu J., Ma C., Li J., Li M., Tang B., Yuan Z. (2020) Microglial autophagy defect causes Parkinson disease-like symptoms by accelerating inflammasome activation in mice. Autophagy, 16(12), 2193\u20132205.","DOI":"10.1080\/15548627.2020.1719723"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Jin M.M., Wang F., Qi D., Liu W.W., Gu C., Mao C.J., Yang Y.P., Zhao Z., Hu L.F., Liu C.F. (2018) A critical role of autophagy in regulating microglia polarization in neurodegeneration. Front. Aging Neurosci., 10, 378.","DOI":"10.3389\/fnagi.2018.00378"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Huang T., Sun C., Du F., Chen Z.J. (2025) STING-induced noncanonical autophagy regulates endolysosomal homeostasis. Proc. Natl. Acad. Sci. USA, 122(8), e2415422122.","DOI":"10.1073\/pnas.2415422122"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Dhapola R., Paidlewar M., Kumari S., Sharma P., Vellingiri B., Medhi B., HariKrishnaReddy D. (2025) cGAS-STING and neurodegenerative diseases: a molecular crosstalk and therapeutic perspective. Int. Immunopharmacol., 159, 114902.","DOI":"10.1016\/j.intimp.2025.114902"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"Bodur C., Kazyken D., Huang K., Ekim Ustunel B., Siroky K.A., Tooley A.S., Gonzalez I.E., Foley D.H., Acosta-Jaquez H.A., Barnes T.M., Steinl G.K., Cho K.-W., Lumeng C.N., Riddle S.M., Myers M.G. Jr, Fingar D.C. (2018) The IKK-related kinase TBK1 activates mTORC1 directly in response to growth factors and innate immune agonists. EMBO J., 37(1), 19\u201338.","DOI":"10.15252\/embj.201696164"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"Murayama G., Chiba A., Kuga T., Makiyama A., Yamaji K., Tamura N., Miyake S. (2020) Inhibition of mTOR suppresses IFN\u03b1 production and the STING pathway in monocytes from systemic lupus erythematosus patients. Rheumatology, 59(10), 2992\u20133002.","DOI":"10.1093\/rheumatology\/keaa060"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"Zheng Z.-H., Wang J.-J., Lin J.-G., Ye W.-L., Zou J.-M., Liang L.-Y., Yang P.-L., Qiu W.-L., Li Y.-Y., Yang S.-J., Zhao M., Zhou Q., Li C.-Z., Li M., Li Z.-M., Zhang D.-M., Liu P.-Q., Liu Z.-P. (2024) Cytosolic DNA initiates a vicious circle of aging-related endothelial inflammation and mitochondrial dysfunction via STING: the inhibitory effect of Cilostazol. Acta Pharmacol. Sin., 45, 1879\u20131897.","DOI":"10.1038\/s41401-024-01281-0"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"El-Marasy S.A., Abo El-Nasr N.M.E., ElMosbah D.E., Elbaset M. (2025) Cilostazol ameliorates cisplatin-induced nephrotoxicity via modulation of PI3K\/AKT\/mTOR signaling pathway and autophagy in rats. Toxicol. Mech. Methods, 35(9), 1496\u20131509.","DOI":"10.1080\/15376516.2025.2545577"},{"key":"ref65","doi-asserted-by":"publisher","unstructured":"Tang Z., Xing C., Araszkiewicz A., Yang K., Huai W., Jeltema D., Dobbs N., Zhang Y., Sun L.O., Yan N. (2025) STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation in lysosomal storage disorders. Mol. Cell., 85(8), 1624\u20131639.e5.","DOI":"10.1016\/j.molcel.2025.03.008"},{"key":"ref66","doi-asserted-by":"publisher","unstructured":"Borsche M., K\u00f6nig I.R., Delcambre S., Petrucci S., Balck A., Br\u00fcggemann N., Zimprich A., Wasner K., Pereira S.L., Avenali M., Deuschle C., Badanjak K., Ghelfi J., Gasser T., Kasten M., Rosenstiel P., Lohmann K., Brockmann K., Valente E.M., Youle R.J., Gr\u00fcnewald A., Klein C. (2020) Mitochondrial damage-associated inflammation highlights biomarkers in PRKN\/PINK1 parkinsonism. Brain, 143(10), 3041\u20133051.","DOI":"10.1093\/brain\/awaa246"},{"key":"ref67","doi-asserted-by":"publisher","unstructured":"Frosch M., Prinz M. (2024) Novel pathomechanistic insights into lysosomal storage disorders: how neuron-intrinsic cGAS-STING signaling drives disease progression. Signal Transduct. Target Ther., 9, 203.","DOI":"10.1038\/s41392-024-01901-5"},{"key":"ref68","doi-asserted-by":"publisher","unstructured":"Hancock-Cerutti W., Wu Z., Xu P., Yadavalli N., Leonzino M., Tharkeshwar A.K., Ferguson S.M., Shadel G.S., de Camilli P. (2022) ER-lysosome lipid transfer protein VPS13C\/PARK23 prevents aberrant mtDNA-dependent STING signaling. J. Cell Biol., 221(7), e202106046.","DOI":"10.1083\/jcb.202106046"},{"key":"ref69","doi-asserted-by":"publisher","unstructured":"Chu T.-T., Tu X., Yang K., Wu J., Repa J.J., Yan N. (2021) Tonic prime-boost of STING signalling mediates Niemann-Pick disease type C. Nature, 596(7873), 570\u2013575.","DOI":"10.1038\/s41586-021-03762-2"},{"key":"ref70","doi-asserted-by":"publisher","unstructured":"Martini-Stoica H., Xu Y., Ballabio A., Zheng H. (2016) The autophagy-lysosomal pathway in neurodegeneration: a TFEB perspective. Trends. Neurosci., 39(4), 221\u2013234.","DOI":"10.1016\/j.tins.2016.02.002"},{"key":"ref71","doi-asserted-by":"publisher","unstructured":"Vila I.K., Laguette N. (2023) The unexpected role of the STING protein in lipid metabolism. Comptes Rendus Biologies, 346, 29\u201333.","DOI":"10.5802\/crbiol.110"},{"key":"ref72","doi-asserted-by":"publisher","unstructured":"Abe T., Barber G.N. (2014) Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-\u03baB activation through TBK1. J. Virol., 88(10), 5328\u20135341.","DOI":"10.1128\/jvi.00037-14"},{"key":"ref73","doi-asserted-by":"publisher","unstructured":"Decout A., Katz J.D., Venkatraman S., Ablasser A. (2021) The cGAS-STING pathway as a therapeutic target in inflammatory diseases. Nat. Rev. Immunol., 21(9), 548\u2013569.","DOI":"10.1038\/s41577-021-00524-z"},{"key":"ref74","doi-asserted-by":"publisher","unstructured":"Mazzulli J.R., Xu Y.-H., Sun Y., Knight A.L., McLean P.J., Caldwell G.A., Sidransky E., Grabowski G.A., Krainc D. (2011) Gaucher disease glucocerebrosidase and \u03b1-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell, 146(1), 37\u201352.","DOI":"10.1016\/j.cell.2011.06.001"},{"key":"ref75","doi-asserted-by":"publisher","unstructured":"Kiechle M., Grozdanov V., Danzer K.M. (2020) The role of lipids in the initiation of \u03b1-synuclein misfolding. Front. Cell Dev. Biol., 8, 562241.","DOI":"10.3389\/fcell.2020.562241"},{"key":"ref76","doi-asserted-by":"publisher","unstructured":"Galvagnion C. (2017) The role of lipids interacting with \u03b1-synuclein in the pathogenesis of Parkinson\u2019s disease. J. Parkinsons Dis., 7(3), 433\u2013450.","DOI":"10.3233\/JPD-171103"},{"key":"ref77","doi-asserted-by":"publisher","unstructured":"Galvagnion C., Brown J.W.P., Ouberai M.M., Flagmeier P., Vendruscolo M., Buell A.K., Sparr E., Dobson C.M. (2016) Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of \u03b1-synuclein. Proc. Natl. Acad. Sci. USA, 113(26), 7065\u20137070.","DOI":"10.1073\/pnas.1601899113"},{"key":"ref78","doi-asserted-by":"publisher","unstructured":"Battis K., Xiang W., Winkler J. (2023) The bidirectional interplay of \u03b1-synuclein with lipids in the central nervous system and its implications for the pathogenesis of Parkinson\u2019s disease. Int. J. Mol. Sci., 24(17), 13270.","DOI":"10.3390\/ijms241713270"},{"key":"ref79","doi-asserted-by":"publisher","unstructured":"Qiao L., Hamamichi S., Caldwell K.A., Caldwell G.A., Yacoubian T.A., Wilson S., Xie Z.-L., Speake L.D., Parks R., Crabtree D., Liang Q., Crimmins S., Schneider L., Uchiyama Y., Iwatsubo T., Zhou Y., Peng L., Lu Y., Standaert D.G., Walls K.C., Shacka J.J., Roth K.A., Zhang J. (2008) Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity. Mol. Brain, 1, 17.","DOI":"10.1186\/1756-6606-1-17"},{"key":"ref80","doi-asserted-by":"publisher","unstructured":"Koike M., Shibata M., Ohsawa Y., Nakanishi H., Koga T., Kametaka S., Waguri S., Momoi T., Kominami E., Peters C., von Figura K., Saftig P., Uchiyama Y. (2003) Involvement of two different cell death pathways in retinal atrophy of cathepsin D-deficient mice. Mol. Cell. Neurosci., 22(2), 146\u2013161.","DOI":"10.1016\/S1044-7431(03)00035-6"},{"key":"ref81","doi-asserted-by":"publisher","unstructured":"Bae E.-J., Yang N.Y., Lee C., Kim S., Lee H.-J., Lee S.-J. (2015) Haploinsufficiency of cathepsin D leads to lysosomal dysfunction and promotes cell-to-cell transmission of \u03b1-synuclein aggregates. Cell Death Dis., 6(10), e1901.","DOI":"10.1038\/cddis.2015.283"},{"key":"ref82","doi-asserted-by":"publisher","unstructured":"Kim Y.C., Guan K.-L. (2015) MTOR: a pharmacologic target for autophagy regulation. J. Clin. Invest., 125(1), 25\u201332.","DOI":"10.1172\/JCI73939"},{"key":"ref83","doi-asserted-by":"publisher","unstructured":"Sarkar S. (2013) Regulation of autophagy by mTOR-dependent and mTOR-independent pathways: autophagy dysfunction in neurodegenerative diseases and therapeutic application of autophagy enhancers. Biochem. Soc. Trans., 41(5), 1103\u20131130.","DOI":"10.1042\/BST20130134"},{"key":"ref84","doi-asserted-by":"publisher","unstructured":"Kang R., Zeh H.J., Lotze M.T., Tang D. (2011) The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ., 18(4), 571\u2013580.","DOI":"10.1038\/cdd.2010.191"},{"key":"ref85","doi-asserted-by":"publisher","unstructured":"Zhu Z., Yang C., Iyaswamy A., Krishnamoorthi S., Sreenivasmurthy S.G., Liu J., Wang Z., Tong B.C.-K., Song J., Lu J., Cheung K.-H., Li M. (2019) Balancing mTOR signaling and autophagy in the treatment of Parkinson\u2019s disease. Int. J. Mol. Sci., 20(3), 728.","DOI":"10.3390\/ijms20030728"},{"key":"ref86","doi-asserted-by":"publisher","unstructured":"Falkenburger B.H., Saridaki T., Dinter E. (2016) Cellular models for Parkinson\u2019s disease. J. Neurochem., 139(Suppl 1), 121\u2013130.","DOI":"10.1111\/jnc.13618"},{"key":"ref87","doi-asserted-by":"publisher","unstructured":"Martirosyan A., Ansari R., Pestana F., Hebestreit K., Gasparyan H., Aleksanyan R., Hnatova S., Poovathingal S., Marneffe C., Thal D.R., Kottick A., Hanson-Smith V.J., Guelfi S., Plumbly W., Belgard T.G., Metzakopian E., Holt M.G. (2024) Unravelling cell type-specific responses to Parkinson\u2019s disease at single cell resolution. Mol. Neurodegener., 19, 7.","DOI":"10.1186\/s13024-023-00699-0"},{"key":"ref88","doi-asserted-by":"publisher","unstructured":"Booth H.D.E., Hirst W.D., Wade-Martins R. (2017) The role of astrocyte dysfunction in Parkinson\u2019s disease pathogenesis. Trends Neurosci., 40(6), 358\u2013370.","DOI":"10.1016\/j.tins.2017.04.001"}],"container-title":["Biomeditsinskaya Khimiya"],"original-title":[],"language":"ru","deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T17:51:40Z","timestamp":1772646700000},"score":1,"resource":{"primary":{"URL":"http:\/\/pbmc.ibmc.msk.ru\/en\/article-en\/PBMC-2026-72-1-42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":88,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026]]},"published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.18097\/pbmcr1616","relation":{},"ISSN":["2310-6905","2310-6972"],"issn-type":[{"value":"2310-6905","type":"electronic"},{"value":"2310-6972","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]}}}