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Relative Levels of DNM2, EPN2, and EXOC4 Gene Expression in Peripheral Blood of Parkinson’s Disease Patients

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Abstract

Parkinson’s disease (PD) is a widespread neurological disorder, which is associated with degeneration of dopaminergic neurons in the substantia nigra. The hallmark of this disease is its long latency period, which makes the search for prognostic biomarkers an essential task. To study the changes in gene expression in the peripheral blood of patients at early stages of PD, who received no treatment, is an approach that can be employed for PD biomarker detection. Data have recently been obtained indicating that impaired membrane transport may play an important role in PD pathogenesis. For this reason, in the present work, changes in the relative mRNA levels for the DNM2, EPN2, and EXOC4 genes in the peripheral blood of treated and untreated Parkinson’s disease patients have been analyzed. Two groups of patients with Parkinson’s disease and two comparison groups, a neurological control and healthy volunteers, were included in the present study. mRNA levels were studied using reverse transcription and real-time PCR (TaqMan technology). The study revealed no significant changes in the expression levels of the studied genes in the group of untreated PD patients. However, in the group of PD patients, who received treatment, statistically significant changes in the DNM2 gene expression at mRNA level have been observed. The results of the present work suggest that the DNM2, EPN2, and EXOC4 genes are not involved in the pathogenesis of Parkinson’s disease at the mRNA level in the patients with early PD and, therefore, cannot be used as prognostic biomarkers for this disease. The changes in the expression of the DNM2 gene in the treated PD patients suggest that this gene is involved in processes associated with dopamine agonist therapy.

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REFERENCES

  1. Poewe, W., Seppi, K., Tanner, C.M., Halliday, G.M., Brundin, P., Volkmann, J., et al., Parkinson disease, Nat. Rev. Dis. Primers, 2017, vol. 3, p. 17013. https://doi.org/10.1038/nrdp.2017.13

    Article  PubMed  Google Scholar 

  2. Zeng, X.S., Geng, W.S., Jia, J.J., Chen, L., and Zhang, P.P., Cellular and molecular basis of neurodegeneration in Parkinson disease, Front. Aging Neurosci., 2018, vol. 10, p. 109. https://doi.org/10.3389/fnagi.2018.00109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Borrageiro, G., Haylett, W., and Seedat, S., A review of genome-wide transcriptomics studies in Parkinson’s disease, Eur. J. Neurosci., 2018, vol. 47, no. 1, pp. 1–16. https://doi.org/10.1111/ejn.13760

    Article  PubMed  Google Scholar 

  4. Simunovic, F., Yi, M., Wang, Y., Macey, L., Brown, L.T., Krichevsky, A.M., et al., Gene expression profiling of substantia nigra dopamine neurons: Further insights into Parkinson’s disease pathology, Brain: J. Neurol., 2009, vol. 132, no. 7, pp. 1795–1809. https://doi.org/10.1093/brain/awn323

    Article  Google Scholar 

  5. Bossers, K., Meerhoff, G., Balesar, R., van Dongen, J.W., Kruse, C.G., Swaab, D.F., et al., Analysis of gene expression in Parkinson’s disease: possible involvement of neurotrophic support and axon guidance in dopaminergic cell death, Brain Pathol. (Zurich, Switz.), 2009, vol. 19, no. 1, pp. 91–107. https://doi.org/10.1111/j.1750-3639.2008.00171.x

  6. Scherzer, C.R., Eklund, A.C., Morse, L.J., Liao, Z., Locascio, J.J., Fefer, D., et al., Molecular markers of early Parkinson’s disease based on gene expression in blood, Proc. Natl. Acad. Sci. U. S. A., 2007, vol. 104, no. 3, pp. 955–960. https://doi.org/10.1073/pnas.0610204104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Caronti, B., Tanda, G., Colosimo, C., Ruggieri, S., Calderaro, C., Palladini, G., et al., Reduced dopamine in peripheral blood lymphocytes in Parkinson’s disease, Neuroreport, 1999, vol. 10, no. 14, pp. 2907–2910. https://doi.org/10.1097/00001756-199909290-00006

    Article  CAS  PubMed  Google Scholar 

  8. Barbanti, P., Fabbrini, G., Ricci, A., Cerbo, R., Bronzetti, E., Caronti, B., et al., Increased expression of dopamine receptors on lymphocytes in Parkinson’s disease, Mov. Disord., 1999, vol. 14, no. 5, pp. 764–771. https://doi.org/10.1002/1531-8257(199909)14:5%3C764::aidmds1008%3E3.0.co;2-w

    Article  CAS  PubMed  Google Scholar 

  9. Alieva, A.K., Filatova, E.V., Kolacheva, A.A., Rudenok, M.M., Slominsky, P.A., Ugrumov, M.V., et al., Transcriptome profile changes in mice with MFTP-induced early stages of Parkinson’s disease, Mol. Neurobiol., 2017, vol. 54, no. 9, pp. 6775–6784. https://doi.org/10.1007/s12035-016-0190-y

    Article  CAS  PubMed  Google Scholar 

  10. Kalia, L.V. and Lang, A.E., Parkinson’s disease, Lancet, 2015, vol. 386, no. 9996, pp. 896–912. https://doi.org/10.1016/S0140-6736(14)61393-3

    Article  CAS  PubMed  Google Scholar 

  11. Hasegawa, T., Sugeno, N., Kikuchi, A., Baba, T., and Aoki, M., Membrane trafficking illuminates a path to Parkinson’s disease, Tohoku J. Exp. Med., 2017, vol. 242, no. 1, pp. 63–76. https://doi.org/10.1620/tjem.242.63

    Article  CAS  PubMed  Google Scholar 

  12. Sheehan, P. and Yue, Z., Deregulation of autophagy and vesicle trafficking in Parkinson’s disease, Neurosci. Lett., 2019, vol. 697, pp. 59–65. https://doi.org/10.1016/j.neulet.2018.04.013

    Article  CAS  PubMed  Google Scholar 

  13. Alieva, A., Shadrina, M.I., Filatova, E.V., Karabanov, A.V., Illarioshkin, S.N., Limborska, S.A., et al., Involvement of endocytosis and alternative splicing in the formation of the pathological process in the early stages of Parkinson’s disease, BioMed Res. Int., 2014, vol. 2014, p. 718732. https://doi.org/10.1155/2014/718732

    Article  PubMed  PubMed Central  Google Scholar 

  14. Starovatykh, Yu.S., Rudenok, M.M., Karabanov, A.V., Illarioshkin, S.N., Slominsky, P.A., Shadrina, M.I., and Alieva, A.Kh., Analysis of the expression of genes CLN3, GABBR1 and WFS1 in patients with Parkinson’s disease, Mol. Genet., Microbiol. Virol., 2020, vol. 35, no. 2, p. 85. https://doi.org/10.3103/S089141682002010X

    Article  Google Scholar 

  15. Rudenok, M.M., Alieva, A.Kh., Nikolaev, M.A., Kolacheva, A.A., Ugryumov, M.V., Pchelina, S.N., et al., Possible involvement of genes related to lysosomal storage disorders in the pathogenesis of Parkinson’s disease, Mol. Biol., 2019, vol. 53, no. 1, pp. 24–31. https://doi.org/10.1134/S002689331901014X

    Article  CAS  Google Scholar 

  16. Rosenthal, J.A., Chen, H., Slepnev, V.I., Pellegrini, L., Salcini, A.E., Di Fiore, P.P., et al., The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module, J. Biol. Chem., 1999, vol. 274, no. 48, pp. 33959–33965. https://doi.org/10.1074/jbc.274.48.33959

    Article  CAS  PubMed  Google Scholar 

  17. Munson, M. and Novick, P., The exocyst defrocked, a framework of rods revealed, Nat. Struct. Mol. Biol., 2006, vol. 13, no. 7, pp. 577–581. https://doi.org/10.1038/nsmb1097

    Article  CAS  PubMed  Google Scholar 

  18. Lalli, G. and Hall, A., Ral GTPases regulate neurite branching through GAP-43 and the exocyst complex, J. Cell Biol., 2005, vol. 171, no. 5, pp. 857–869. https://doi.org/10.1083/jcb.200507061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sans, N., Prybylowski, K., Petralia, R.S., Chang, K., Wang, Y.X., Racca, C., et al., NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex, Nat. Cell Biol., 2003, vol. 5, no. 6, pp. 520–530. https://doi.org/10.1038/ncb990

    Article  CAS  PubMed  Google Scholar 

  20. Kennedy, M.J. and Ehlers, M.D., Mechanisms and function of dendritic exocytosis, Neuron, 2011, vol. 69, no. 5, pp. 856–875. https://doi.org/10.1016/j.neuron.2011.02.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mellone, M., Zianni, E., Stanic, J., Campanelli, F., Marino, G., Ghiglieri, V., et al., NMDA receptor GluN2D subunit participates to levodopa-induced dyskinesia pathophysiology, Neurobiol. Dis., 2019, no. 121, pp. 338–349. https://doi.org/10.1016/j.nbd.2018.09.021

  22. Kobylecki, C., Cenci, M.A., Crossman, A.R., and Ravenscroft, P., Calcium-permeable AMPA receptors are involved in the induction and expression of l-DOPA-induced dyskinesia in Parkinson’s disease, J. Neurochem., 2010, vol. 114, no. 2, pp. 499–511. https://doi.org/10.1111/j.1471-4159.2010.06776.x

    Article  CAS  PubMed  Google Scholar 

  23. Rascol, O., Fox, S., Gasparini, F., Kenney, C., Di Paolo, T., and Gomez-Mancilla, B., Use of metabotropic glutamate 5-receptor antagonists for treatment of levodopa-induced dyskinesias, Parkinsonism Relat. Disord., 2014, vol. 20, no. 9, pp. 947–956. https://doi.org/10.1016/j.parkreldis.2014.05.003

    Article  PubMed  Google Scholar 

  24. Szénási, G., Vegh, M., Szabo, G., Kertesz, S., Kapus, G., Albert, M., et al., 2,3-Benzodiazepine-type AMPA receptor antagonists and their neuroprotective effects, Neurochem. Int., 2008, vol. 52, nos. 1–2, pp. 166–183. https://doi.org/10.1016/j.neuint.2007.07.002

    Article  CAS  PubMed  Google Scholar 

  25. Grassart, A., Cheng, A.T., Hong, S.H., Zhang, F., Zenzer, N., Feng, Y., et al., Actin and dynamin2 dynamics and interplay during clathrin-mediated endocytosis, J. Cell Biol., 2014, vol. 205, no. 5, pp. 721–735. https://doi.org/10.1083/jcb.201403041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Koutsopoulos, O.S., Koch, C., Tosch, V., Böhm, J., North, K.N., and Laporte, J., Mild functional differences of dynamin 2 mutations associated to centronuclear myopathy and Charcot–Marie–Tooth peripheral neuropathy, PLoS One, 2011, vol. 6, no. 11, p. e27498. https://doi.org/10.1371/journal.pone.0027498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Stafa, K., Tsika, E., Moser, R., Musso, A., Glauser, L., Jones, A., et al., Functional interaction of Parkinson’s disease-associated LRRK2 with members of the dynamin GTPase superfamily, Hum. Mol. Genet., 2014, vol. 23, no. 8, pp. 2055–2077. https://doi.org/10.1093/hmg/ddt600

    Article  CAS  PubMed  Google Scholar 

  28. Ferguson, S.S., Zhang, J., Barak, L.S., and Caron, M.G., Molecular mechanisms of G protein-coupled receptor desensitization and resensitization, Life Sci., 1998, vol. 62, nos. 17–18, pp. 1561–1565. https://doi.org/10.1016/S0024-3205(98)00107-6

    Article  CAS  PubMed  Google Scholar 

  29. Sander, C.Y., Hooker, J.M., Catana, C., Rosen, B.R., and Mandeville, J.B., Imaging agonist-induced D2/D3 receptor desensitization and internalization in vivo with PET/fMRI, Neuropsychopharmacology, 2016, vol. 41, no. 5, pp. 1427–1436. https://doi.org/10.1038/npp.2015.296

    Article  CAS  PubMed  Google Scholar 

  30. Kabbani, N., Jeromin, A., and Levenson, R., Dynamin-2 associates with the dopamine receptor signalplex and regulates internalization of activated D2 receptors, Cell. Signalling, 2004, vol. 16, no. 4, pp. 497–503. https://doi.org/10.1016/j.cellsig.2003.09.011

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the Russian Science Foundation, grant no. 20-15-00262. Equipment of the Center for Collective Use “Institute of Molecular Genetics” of the Kurchatov Institute National Research Center was used.

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Authors and Affiliations

  1. Institute of Molecular Genetics, Kurchatov Institute National Research Center, 123182, Moscow, Russia

    E. I. Semenova, M. M. Rudenok, A. Kh. Alieva, P. A. Slominsky & M. I. Shadrina

  2. Neurology Research Center, 125367, Moscow, Russia

    A. V. Karabanov & S. N. Illarioshkin

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  1. E. I. Semenova
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  6. P. A. Slominsky
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Correspondence to E. I. Semenova.

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Conflict of interests. The authors declare that they have no conflict of interest.

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants involved in the study.

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Translated by E. Martynova

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Semenova, E.I., Rudenok, M.M., Alieva, A.K. et al. Relative Levels of DNM2, EPN2, and EXOC4 Gene Expression in Peripheral Blood of Parkinson’s Disease Patients. Mol. Genet. Microbiol. Virol. 36, 139–143 (2021). https://doi.org/10.3103/S0891416821030071

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