Группа по изучению роли дисфункции лизосом в развитии нейродегенеративных заболеваний

Научные интересы сосредоточены на изучении молекулярных механизмов нейродегенеративных заболеваний, таких как болезнь Паркинсона, деменция с тельцами Леви и множественная системная атрофия. Основное внимание уделяется исследованиям, посвященным поиску биомаркеров и потенциальных терапевтических мишеней, в том числе и на основе анализа транскриптомных данных с помощью биоинформатических подходов. Еще одно направление исследований заключается в скрининге препаратов, нацеленных на выявленные мишени, на пациент-специфичных клетках и клеточных линиях для выявления потенциальных препаратов для терапии исследуемых заболеваний. Ещё одно направление исследований заключается в биоинформатическом анализе данных полноэкзомного секвенирования для поиска новых и известных вариантов, связанных с различными заболеваниями, в том числе болезни Паркинсона.

Список наиболее значимых публикаций

Статьи

1. Bezrukova AI, Basharova KS, Baydakova GV, Zakharova EY, N Pchelina S, Usenko TS. 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 — Assessment of the Prospects of Parkinson’s Disease Therapy. Biochemistry (Mosc). 2024 Jul;89(7):1300-1312. doi: 10.1134/S0006297924070113. PMID: 39218026.

2. Usenko TS, Timofeeva A, Beletskaia M, Basharova K, Baydakova G, Bezrukova A, Grunina M, Emelyanov A, Miliukhina I, Zakharova E, Pchelina S. The Effect of p.G2019S Mutation in the <i>LRRK2</i> Gene on the Activity of Lysosomal Hydrolases and the Clinical Features of Parkinson’s Disease Associated with p.N370S Mutation in the <i>GBA1</i> Gene. J Integr Neurosci. 2024 Jan 16;23(1):16. doi: 10.31083/j.jin2301016. PMID: 38287861.

3. Usenko T, Bezrukova A, Basharova K, Baydakova G, Shagimardanova E, Blatt N, Rizvanov A, Limankin O, Novitskiy M, Shnayder N, Izyumchenko A, Nikolaev M, Zabotina A, Lavrinova A, Kulabukhova D, Nasyrova R, Palchikova E, Zalutskaya N, Miliukhina I, Barbitoff Y, Glotov O, Glotov A, Taraskina A, Neznanov N, Zakharova E, Pchelina S. Altered Sphingolipid Hydrolase Activities and Alpha- Synuclein Level in Late-Onset Schizophrenia. Metabolites. 2023 Dec 31;14(1):30. doi: 10.3390/metabo14010030. PMID: 38248833; PMCID: PMC10819534.

4. Usenko T, Bezrukova A, Rudenok MM, Basharova K, Shadrina MI, Slominsky PA, Zakharova E, Pchelina S. Whole Transcriptome Analysis of Substantia Nigra in Mice with MPTP-Induced Parkinsonism Bearing Defective Glucocerebrosidase Activity. Int J Mol Sci. 2023 Jul 29;24(15):12164. doi: 10.3390/ijms241512164. PMID: 37569538; PMCID: PMC10418497.

5. Usenko TS, Senkevich KA, Basharova KS, Bezrukova AI, Baydakova GV, Tyurin AA, Beletskaya MV, Kulabukhova DG, Grunina MN, Emelyanov AK, Miliukhina IV, Timofeeva AA, Zakharova EY, Pchelina SN. LRRK2 exonic variants are associated with lysosomal hydrolase activities and lysosphingolipid alterations in Parkinson’s disease. Gene. 2023 Oct 5;882:147639. doi: 10.1016/j.gene.2023.147639. Epub 2023 Jul 18. PMID: 37473971.

6. Usenko T, Miroshnikova V, Bezrukova A, Basharova K, Landa S, Korobova Z, Liubimova N, Vlasov I, Nikolaev M, Izyumchenko A, Gavrilova E, Shlyk I, Chernitskaya E, Kovalchuk Y, Slominsky P, Totolian A, Polushin Y, Pchelina S. Fraction of plasma exomeres and low-density lipoprotein cholesterol as a predictor of fatal outcome of COVID-19. PLoS One. 2023 Feb 9;18(2):e0278083. doi: 10.1371/journal.pone.0278083. PMID: 36758022; PMCID: PMC9910704.

7. Kopytova AE, Usenko TS, Baydakova GV, Nikolaev MA, Senkevich KA, Izyumchenko
AD, Tyurin AA, Miliukhina IV, Emelyanov AK, Zakharova EY, Pchelina SN. Could
Blood Hexosylsphingosine Be a Marker for Parkinson’s Disease Linked with GBA1
Mutations? Mov Disord. 2022 Aug;37(8):1779-1781. doi: 10.1002/mds.29132. Epub
2022 Jul 6. PMID: 35792565.

8. Usenko TS, Senkevich KA, Bezrukova AI, Baydakova GV, Basharova KS, Zhuravlev AS, Gracheva EV, Kudrevatykh AV, Miliukhina IV, Krasakov IV, Khublarova LA, Fursova IV, Zakharov DV, Timofeeva AA, Irishina YA, Palchikova EI, Zalutskaya NM, Emelyanov AK, Zakharova EY, Pchelina SN. Impaired Sphingolipid Hydrolase Activities in Dementia with Lewy Bodies and Multiple System Atrophy. Mol Neurobiol. 2022 Apr;59(4):2277-2287. doi: 10.1007/s12035-021-02688-0. Epub 2022 Jan 23. PMID: 35066761.

9. Vlasov I, Panteleeva A, Usenko T, Nikolaev M, Izumchenko A, Gavrilova E, Shlyk I, Miroshnikova V, Shadrina M, Polushin Y, Pchelina S, Slonimsky P. Transcriptomic Profiles Reveal Downregulation of Low-Density Lipoprotein Particle Receptor Pathway Activity in Patients Surviving Severe COVID-19. Cells. 2021 Dec 10;10(12):3495. doi: 10.3390/cells10123495. PMID: 34944005; PMCID: PMC8700658.

10. Usenko T, Bezrukova A, Basharova K, Panteleeva A, Nikolaev M, Kopytova A, Miliukhina I, Emelyanov A, Zakharova E, Pchelina S. Comparative Transcriptome Analysis in Monocyte-Derived Macrophages of Asymptomatic <i>GBA</i> Mutation Carriers and Patients with GBA-Associated Parkinson’s Disease. Genes (Basel). 2021 Sep 29;12(10):1545. doi: 10.3390/genes12101545. PMID: 34680941; PMCID: PMC8535749.

11. Emelyanov A, Usenko T, Nikolaev M, Senkevich K, Kulabukhova D, Lavrinova A, Andoskin P, Miliukhina I, Pchelina S. Increased α-Synuclein Level in CD45+ Blood Cells in Asymptomatic Carriers of GBA Mutations. Mov Disord. 2021 Aug;36(8):1997-1998. doi: 10.1002/mds.28688. PMID: 34409693.

12. Kopytova AE, Rychkov GN, Nikolaev MA, Baydakova GV, Cheblokov AA, Senkevich KA, Bogdanova DA, Bolshakova OI, Miliukhina IV, Bezrukikh VA, Salogub GN, Sarantseva SV, Usenko TC, Zakharova EY, Emelyanov AK, Pchelina SN. Ambroxol increases glucocerebrosidase (GCase) activity and restores GCase translocation in primary patient-derived macrophages in Gaucher disease and Parkinsonism. Parkinsonism Relat Disord. 2021 Mar;84:112-121. doi: 10.1016/j.parkreldis.2021.02.003. Epub 2021 Feb 10. PMID: 33609962.

13. Senkevich KA, Kopytova AE, Usenko TS, Emelyanov AK, Pchelina SN. Parkinson’s Disease Associated with GBA Gene Mutations: Molecular Aspects and Potential Treatment Approaches. Acta Naturae. 2021 Apr-Jun;13(2):70-78. doi: 10.32607/actanaturae.11031. PMID: 34377557; PMCID: PMC8327146.

14. Usenko TS, Nikolaev MA, Miliukhina IV, Bezrukova AI, Senkevich KA, Gomzyakova NA, Beltceva YA, Zalutskaya NM, Gracheva EV, Timofeeva AA, Petrova OA, Semenov AV, Lubimova NE, Totolyan AA, Pchelina SN. Plasma cytokine profile in synucleinophaties with dementia. J Clin Neurosci. 2020 Aug;78:323-326. doi: 10.1016/j.jocn.2020.04.058. Epub 2020 Apr 23. PMID: 32336641.

15. Miliukhina IV, Usenko TS, Senkevich KA, Nikolaev MA, Timofeeva AA, Agapova
EA, Semenov AV, Lubimova NE, Totolyan AA, Pchelina SN. Plasma Cytokines Profile
in Patients with Parkinson’s Disease Associated with Mutations in GBA Gene. Bull Exp Biol Med. 2020 Feb;168(4):423-426. doi: 10.1007/s10517-020-04723-x. Epub 2020 Mar 7. PMID: 32146630.

16. Emelyanov AK, Usenko TS, Tesson C, Senkevich KA, Nikolaev MA, Miliukhina IV, Kopytova AE, Timofeeva AA, Yakimovsky AF, Lesage S, Brice A, Pchelina SN. Mutation analysis of Parkinson’s disease genes in a Russian data set. Neurobiol Aging. 2018 Nov;71:267.e7-267.e10. doi: 10.1016/j.neurobiolaging.2018.06.027. Epub 2018 Jul 9. PMID: 30146349.

17. Elsayed LE, Drouet V, Usenko T, Mohammed IN, Hamed AA, Elseed MA, Salih MA, Koko ME, Mohamed AY, Siddig RA, Elbashir MI, Ibrahim ME, Durr A, Stevanin G, Lesage S, Ahmed AE, Brice A. A Novel Nonsense Mutation in DNAJC6 Expands the Phenotype of Autosomal-Recessive Juvenile-Onset Parkinson’s Disease. Ann Neurol. 2016 Feb;79(2):335-7. doi: 10.1002/ana.24591. Epub 2016 Jan 19. PMID: 26703368.

18. Lesage S, Drouet V, Majounie E, Deramecourt V, Jacoupy M, Nicolas A, Cormier-Dequaire F, Hassoun SM, Pujol C, Ciura S, Erpapazoglou Z, Usenko T, Maurage CA, Sahbatou M, Liebau S, Ding J, Bilgic B, Emre M, Erginel-Unaltuna N, Guven G, Tison F, Tranchant C, Vidailhet M, Corvol JC, Krack P, Leutenegger AL, Nalls MA, Hernandez DG, Heutink P, Gibbs JR, Hardy J, Wood NW, Gasser T, Durr A, Deleuze JF, Tazir M, Destée A, Lohmann E, Kabashi E, Singleton A, Corti O, Brice A; French Parkinson’s Disease Genetics Study (PDG); International Parkinson’s Disease Genomics Consortium (IPDGC). Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy. Am J Hum Genet. 2016 Mar 3;98(3):500-513. doi: 10.1016/j.ajhg.2016.01.014. PMID: 26942284; PMCID: PMC4800038.