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An Infection Hypothesis of Parkinson’s Disease

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Parkinson’s disease (PD) is a multifactorial progressive neurodegenerative disease characterized by predominant degeneration of dopaminergic neurons in the substantia nigra. Neuroinflammation is one of the key components of the pathogenesis of PD, though the mechanisms initiating the inflammatory process and the triggers launching the irreversible neuroinflammatory process in patients with PD thus far remain unstudied. The present review addresses the role of infection-related factors in the etiology of PD. We evaluate the question of whether PD is the result of prior viral or bacterial infections due to the action of endotoxins on brain cells initiating the development of the inflammatory process in the CNS. Some cellular and animal models of PD of the infection type are presented and the molecular mechanisms of the development of neuroinflammation and neurodegeneration in these models are laid out. The final part of the review contains an analysis of reports, including those from the authors of this review, on the creation of valid models of the clinical and preclinical stages of PD in animals based on the proteasome inhibitor lactacystin, a metabolite of the soil bacterium Streptomyces sp.

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References

  1. E. I. Gusev, A. B. Gekht, G. R. Popov, et al., Parkinson’s Disease. Clinical Aspects, Diagnosis, and Treatment of Neurodegenerative Diseases: Basic and Applied Aspects, M. V. Ugryumov (ed.), Nauka, Moscow (2010), pp. 52–86.

  2. I. V. Ekimova, D. V. Plaksina, K. V. Lapshina, et al., “Pathological and compensatory processes in a new model of the preclinical stage of Parkinson’s disease in rats,” Acta Naturae, Spec. Iss., No. 1, 50 (2016).

  3. I. V. Ekimova, V. V. Simonova, M. A. Guzeev, et al., “Changes in sleep characteristics in a model of the preclinical stage of Parkinson’s disease in rats based on weakening of the activity of the ubiquitin-proteasome system of the brain,” Zh. Evolyuts. Biokhim. Fiziol., 52, No. 6, 413–422 (2016).

    Google Scholar 

  4. S. N. Illarioshkin, “The course of Parkinson’s disease and approaches to the early diagnosis,” in: Parkinson’s Disease and Motor Disorders. Guidelines for Doctors: Proc. 2nd Nat. Congress on Parkinson’s Disease and Motor Disorders, S. N. Illarioshkin and O. S. Levin (eds.), Moscow (2011), pp. 41–47.

  5. I. V. Milyukhina, M. N. Karpenko, A. A. Timofeeva, et al., “The role of inflammation and the pathogenesis of Parkinson’s disease,” Nevrol. Zh., 18, No. 3, 51–55 (2013).

    Google Scholar 

  6. Yu. F. Pastukhov, “Changes in the characteristics of paradoxical sleep – an early sign of Parkinson’s disease,” Zh. Vyssh. Nerv. Deyat., 63, No. 1, 75–85 (2013).

    CAS  Google Scholar 

  7. Yu. F. Pastukhov, I. V. Ekimova, and A. V. Chesnokova, “Molecular mechanisms of the pathogenesis of Parkinson’s disease and the potentials of preventive therapy,” in: Neurodegenerative Diseases – from Genome to the Whole Body. Part I. Motor Function and its Regulation in Health and Pathology, M. V. Ugryumov (ed.), Nauchnyi Mir, Moscow (2014), pp. 316–355.

  8. Yu. F. Pastukhov, V. V. Simonova, M. A. Guzeev, and I. V. Ekimova, “Molecular mechanisms of sleep impairment at the initial stage of neurodegeneration induced by proteasomal dysfunction,” Acta Naturae, Spec. Iss., No. 1, 52 (2016).

  9. Yu. F. Pastukhov, V. V. Simonova, M. V. Chernyshev, et al., “Signs of sleep impairment and behavior signaling the initial stage of neurodegenerative in a model of Parkinson’s disease,” Zh. Evolyuts. Biokhim. Fiziol., 53, No. 5, 380–384 (2017).

    Google Scholar 

  10. Yu. F. Pastukhov and A. Yu. Chesnokova, “α-Synuclein in the pathogenesis of Parkinson’s disease and other neurodegenerative diseases,” in: Neurodegenerative Diseases: Basic and Applied Aspects, M. V. Ugryumov (ed.), Nauka, Moscow (2010).

  11. Yu. F. Pastukhov, A. Yu. Chesnokova, A. A. Yakimchuk, et al., “Changes in sleep in degeneration of the substantia nigra induced by the proteasome inhibitor lactacystin,” Ros. Fiziol. Zh., 96, No. 12, 1190–1202 (2010).

    CAS  Google Scholar 

  12. D. V. Plaksina, I. V. Ekimova, M. N. Karpenko, and Yu. F. Pastukhov, “Assessment of the functional state of the nigrostrial system of the brain in an experimental model of the preclinical stage of Parkinson’s disease in rats,” Zh. Evolyuts. Biokhim. Fiziol., 53, No. 5, 370–374 (2017).

    Google Scholar 

  13. M. V. Ugryumov, “Translated, personalized, and prophylactic medicine as the basis for the battle with neurodegenerative diseases,” in: Neurodegenerative Diseases – from Genome to the Whole Body, Nauchnyi Mir, Moscow (2014), pp. 316–355.

  14. H. H. Balfour, S. K. Dunmire, and K. A. Hogquist, “Infectious mononucleosis,” Clin. Transl. Immunology, 4, No. 2, 33 (2015).

    Google Scholar 

  15. L. L. Barnes, A. W. Capuano, A. E. Aiello, et al., “Cytomegalovirus infection and risk of Alzheimer disease in older black and white individuals,” J. Infect. Dis., 211, No. 2, 230–237 (2015).

    CAS  PubMed  Google Scholar 

  16. E. Bentea, L. Verbruggen, and A. Massie, “The proteasome inhibition model of Parkinson’s disease,” J. Parkinsons Dis., 7, No. 1, 31–63 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. H. Braak, E. Ghebremedhin, U. Rub, et al., “Stages in the development of Parkinson’s disease related pathology,” Cell Tissue Res., 318, No. 1, 121–134 (2004).

    PubMed  Google Scholar 

  18. X. L. Bu, X. Wang, Y. Xiang, et al., “The association between infectious burden and Parkinson’s disease: a case-control study,” Parkinsonism Relat. Disord., 21, No. 8, 877–881 (2015).

    PubMed  Google Scholar 

  19. A. Cagnin, M. Kassiou, S. R. Meikle, and R. B. Banati, “Positron emission tomography imaging of neuroinflammation,” Neurotherapeutics, 4, No. 3, 443–452 (2007).

    CAS  PubMed  Google Scholar 

  20. G. Çamci and S. Oğuz, “Association between Parkinson’s disease and Helicobacter pylori,” J. Clin. Neurology, 12, No. 2, 147–150 (2016).

    Google Scholar 

  21. P. M. Carvey, Q. Chang, J. W. Lipton, and Z. Ling, “Prenatal exposure to the bacteriotoxin lipopolysaccharide leads to long-term losses of dopamine neurons in offspring: a potential, new model of Parkinson’s disease,” Front. Biosci., 8, 826–837 (2003).

    Google Scholar 

  22. A. Castano, A. J. Herrera, J. Cano, and A. Machado, “Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system,” J. Neurochem., 70, No. 4, 1584–1592 (1998).

    CAS  PubMed  Google Scholar 

  23. G. Chapman, B. L. Beaman, D. A. Loeffler, et al., “In situ hybridization for detection of nocardial 16S rRNA: reactivity within intracellular inclusions in experimentally infected cynomolgus monkeys – and in Lewy body-containing human brain specimens,” Exp. Neurol., 184, No. 2, 715–725 (2003).

    CAS  PubMed  Google Scholar 

  24. A. Charlett, R. J. Dobbs, S. M. Dobbs, et al., “Parkinsonism: siblings share Helicobacter pylori seropositivity and facets of syndrome,” Acta Neurol. Scand., 99, No. 1, 26–35 (1999).

    CAS  PubMed  Google Scholar 

  25. A. Ciechanover and Y. T. Kwon, “Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies,” Exp. Mol. Med., 47, No. 3, е147 (2015).

    Google Scholar 

  26. T. Cross, “Aquatic actinomycetes: A critical survey of the occurrence, growth and role of actinomycetes in aquatic habitats,” J. Appl. Bacteriol., 50, No. 3, 397–423 (1981).

    CAS  PubMed  Google Scholar 

  27. G. Deretzi, J. Kountouras, S. A. Polyzos, et al., “Gastrointestinal immune system and brain dialogue implicated in neuroinflammatory and neurodegenerative diseases,” Curr. Mol. Med., 11, No. 8, 696–707 (2011).

    CAS  PubMed  Google Scholar 

  28. D. T. Dexter and P. Jenner, “Parkinson disease: From pathology to molecular disease mechanisms,” Free Radic. Biol. Med., 62, 132–144 (2013).

    CAS  PubMed  Google Scholar 

  29. S. M. Dobbs, R. J. Dobbs, C. Weller, and A. Charlett, “Link between Helicobacter pylori infection and idiopathic parkinsonism,” Med. Hypotheses, 55, No. 2, 93–98 (2000).

    CAS  PubMed  Google Scholar 

  30. C. T. M. Dow, “M. paratuberculosis and Parkinson’s disease – is this a trigger,” Med. Hypotheses, 83, No. 6, 709–712 (2014).

    PubMed  Google Scholar 

  31. D. Ebrahimi-Fakhari, L. Wahlster, and P. J. McLean, “Protein degradation pathways in Parkinson’s disease: curse or blessing,” Acta Neuropathol., 124, No. 2, 153–172 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. F. Fang, K. Wirdefeldt, A. Jacks, et al., “CNS infections, sepsis and risk of Parkinson’s disease,” Int. J. Epidemiol., 41, No. 4, 1042–1049 (2012).

    PubMed  PubMed Central  Google Scholar 

  33. G. Fenteany and S. L. Schreiber, “Lactacystin, proteasome function, and cell fate,” J. Biol. Chem., 273, No. 15, 8545–8548 (1998).

    CAS  PubMed  Google Scholar 

  34. F. Fornai, P. Lenzi, M. Gesi, et al., “Fine structure and biochemical mechanisms underlying nigrostriatal inclusions and cell death after proteasome inhibition,” J. Neurosci., 23, 8955–8966 (2003).

    CAS  PubMed  Google Scholar 

  35. D. M. Forton, J. M. Allsop, I. J. Cox, et al., “A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection,” AIDS, 19, 53–63 (2005).

    Google Scholar 

  36. H. M. Gao, J. Jiang, B. Wilson, et al., “Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease,” J. Neurochem., 81, No. 6, 1285–1297 (2002).

    CAS  PubMed  Google Scholar 

  37. D. A. Gayle, Z. Ling, C. Tong, et al., “Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-α, interleukin-1β, and nitric oxide,” Dev. Brain Res., 133, No. 1, 27–35 (2002).

    CAS  Google Scholar 

  38. C. H. Hawkes, K. Del Tredici, and H. Braak, “Parkinson’s disease: a dual-hit hypothesis,” Neuropathol. Appl. Neurobiol., 33, No. 6, 599–614 (2007).

    CAS  PubMed  Google Scholar 

  39. N. M. Joseph, B. N. Harish, S. Sistla, et al., “Streptomyces bacteremia in a patient with actinomycotic mycetoma,” J. Infect. Dev. Ctries., 4, No. 4, 249–252 (2010).

    PubMed  Google Scholar 

  40. H. S. Jung, M. M. Ehlers, H. Lombaard, et al., “Etiology of bacterial vaginosis and polymicrobial biofilm formation,” Crit. Rev. Microbiol., 30, 1–17 (2017).

    Google Scholar 

  41. N. Kadoguchi, H. Kimoto, R. Yano, et al., “Failure of acute administration with proteasome inhibitor to provide a model of Parkinson’s disease in mice,” Metab. Brain. Dis., 23, 147–154 (2008).

    CAS  PubMed  Google Scholar 

  42. S. Kohbata, and K. Shimokawa, “Circulating antibody to Nocardia in the serum of patients with Parkinson’s disease,” Adv. Neurology, 60, 355–357 (1992).

    Google Scholar 

  43. J. Konieczny, A. Czarnecka, T. Lenda, et al., “Chronic L-DOPA treatment attenuates behavioral and biochemical deficits induced by unilateral lactacystin administration into the rat substantia nigra,” Behav. Brain Res., 261, 79–88 (2014).

    CAS  PubMed  Google Scholar 

  44. S. J. Kwon, T. B. Ahn, M. Y. Yoon, and B. S. Jeon, “BV-2 stimulation by lactacystin results in a strong inflammatory reaction and apoptotic neuronal death in SH-SY5Y cells,” Brain Res., 1205, 116–121 (2008).

    CAS  PubMed  Google Scholar 

  45. E. Lahner, B. Annibale, and G. Delle Fave, “Systematic review: Helicobacter pylori infection and impaired drug absorption,” Aliment. Pharmacol. Ther., 29, No. 4, 379–386 (2009).

    CAS  PubMed  Google Scholar 

  46. E. Lahner, C. Virili, M. G. Santaguida, et al., “Helicobacter pylori infection and drugs malabsorption,” World J. Gastroenterol., 20, No. 30, 10331–10337 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. T. Laskus, M. Radkowski, D. M. Adair, et al., “Emerging evidence of hepatitis C virus neuroinvasion,” AIDS, 19, 140–144 (2005).

    Google Scholar 

  48. H. J. Lee, S. M. Baek, D. H. Ho, et al., “Dopamine promotes formation and secretion of non-fibrillar alpha-synuclein oligomers,” Exp. Mol. Med., 43, 4, 216–222 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Z. Ling, D. A. Gayle, S. Y. Ma, et al., “In utero bacterial endotoxin exposure causes loss of tyrosine hydroxylase neurons in the postnatal rat midbrain,” Mov. Disord., 17, No. 1, 116–124 (2002).

    PubMed  Google Scholar 

  50. D. A. Loeffler, D. M. Camp, S. Qu, et al., “Characterization of dopamine-depleting activity of Nocardia asteroides strain GUH-2 culture filtrate on PC12 cells,” Microb. Pathog., 37, No. 2, 73–85 (2004).

    CAS  PubMed  Google Scholar 

  51. A. B. Manning-Bog, S. H. Reaney, V. P. Chou, et al., “Lack of nigrostriatal pathology in a rat model of proteasome inhibition,” Ann. Neurol., 60, No. 2, 256–260 (2006).

    PubMed  Google Scholar 

  52. C. N. Martyn and C. Osmond, “Parkinson’s disease and the environment in early life,” J. Neurol. Sci, 132, No. 2, 201–206 (1995).

    CAS  PubMed  Google Scholar 

  53. O. Marques and T. F. Outeiro, “Alpha-synuclein: from secretion to dysfunction and death,” Cell Death Dis., 3, e350 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. B. N. Mathur, M. D. Neely, M. Dyllick-Brenzinger, et al., “Systemic administration of a proteasome inhibitor does not cause nigrostriatal dopamine degeneration,” Brain Res., 1168, 83–89 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. R. M. McManus and M. T. Heneka, “Role of neuroinflammation in neurodegeneration: new insights,” Alzheimers Res. Ther., 9, No. 1, 14 (2017).

    PubMed  PubMed Central  Google Scholar 

  56. K. S. McNaught, L. M. Bjorklund, R. Belizaire, et al., “Proteasome inhibition causes nigral degeneration with inclusion bodies in rats,” Neuroreport, 13, No. 11, 1437–1441 (2002).

    CAS  PubMed  Google Scholar 

  57. K. S. McNaught, R. Belizaire, O. Isacson, et al., “Altered proteasomal function in sporadic Parkinson’s disease,” Exp. Neurol., 179, No. 1, 38–46 (2003).

    CAS  PubMed  Google Scholar 

  58. K. S. McNaught, D. P. Perl, A. L. Brownell, and C. W. Olanow, “Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson’s disease,” Ann. Neurol., 56, No. 1, 149–162 (2004).

    CAS  PubMed  Google Scholar 

  59. J. J. Neher, U. Neniskyte, T. Hornik, and G. C. Brown, “Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo,” Glia, 62, No. 9, 1463–1475 (2014).

    PubMed  PubMed Central  Google Scholar 

  60. C. Niu, J. Me, Q. Pan, and X. Fu, “Nigral degeneration with inclusion body formation and behavioral changes in rats after proteasomal inhibition,” Stereotact. Funct. Neurosurg., 87, No. 2, 69–81 (2009).

    PubMed  PubMed Central  Google Scholar 

  61. C. Noelker, L. Morel, T. Lescot, et al., “Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease,” Sci. Rep., 3, 1393 (2013).

    PubMed  PubMed Central  Google Scholar 

  62. A. Ogata, K. Tashiro, S. Nukuzuma, et al., “A rat model of Parkinson’s disease induced by Japanese encephalitis virus,” J. Neurovirol., 3, No. 2, 141–147 (1997).

    CAS  PubMed  Google Scholar 

  63. E. Okun, K. J. Griffioen, and M. P. Mattson, “Toll-like receptor signaling in neural plasticity and disease,” Trends Neurosci., 34, No. 5, 269–281 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Y. Ouchi, T. Kanno, H. Okada, et al., “Presynaptic and postsynaptic dopaminergic binding densities in the nigrostriatal and mesocortical systems in early Parkinson’s disease: A double-tracer positron emission tomography study,” Ann. Neurol., 46, No. 5, 723–731 (1999).

    CAS  PubMed  Google Scholar 

  65. Y. Ouchi, E. Yoshikawa, Y. Sekine, et al., “Microglial activation and dopamine terminal loss in early Parkinson’s disease,” Ann. Neurol., 57, No. 2, 168–175 (2005).

    CAS  PubMed  Google Scholar 

  66. D. V. Plaksina, M. V. Chernyshev, M. N. Karpenko, et al., “Experimental modeling of a preclinical Parkinson’s disease stage in rats by intranasal lactacystin administration,” Neurodegen. Dis. (Suppl), 17, No. 1, 1655 (2017).

    Google Scholar 

  67. A. Priyadarshi, S. A. Khuder, E. A. Schaub, and S. S. Priyadarshi, “Environmental risk factors and Parkinson’s disease: a metaanalysis,” Environ. Res., 86, No. 2, 122–127 (2001).

    CAS  PubMed  Google Scholar 

  68. S. Sadasivan, B. Sharp, S. Schultz-Cherry, and R. J. Smeyne, “Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis,” Parkinson’s Dis., 3, No. 1, 18 (2017).

    Google Scholar 

  69. M. H. Savolainen, K. Albert, M. Airavaara, and T. T. Myohanen, “Nigral injection of a proteasomal inhibitor, lactacystin, induces widespread glial cell activation and shows various phenotypes of Parkinson’s disease in young and adult mouse,” Exp. Brain Res., 1–14 (2017).

  70. A. H. Schapira, M. W. Cleeter, J. R. Muddle, et al., “Proteasomal inhibition causes loss of nigral tyrosine hydroxylase neurons,” Ann. Neurol., 60, No. 2, 253–255 (2006).

    CAS  PubMed  Google Scholar 

  71. S. A. Staras, S. C. Dollard, K. W. Radford, et al., “Seroprevalence of cytomegalovirus infection in the United States, 1988–1994,” Clin. Infect. Dis., 43, No. 9, 1143–1151 (2006).

    PubMed  Google Scholar 

  72. A. H. Tan, S. Mahadeva, C. Marras, et al., “Helicobacter pylori infection is associated with worse severity of Parkinson’s disease,” Parkinsonism Relat. Disord., 21, No. 3, 221–225 (2015).

    PubMed  Google Scholar 

  73. H. Tomoda and S. Omura, “Lactacystin, a proteasome inhibitor: discovery and its application in cell biology,” Yakugaku Zasshi, 120, No. 10, 935–949 (2000).

    CAS  PubMed  Google Scholar 

  74. S. Toovey, S. S. Jick, and C. R. Meier, “Parkinson’s disease or Parkinson symptoms following seasonal influenza,” Influenza Other Respir. Viruses, 5, No. 5, 328–333 (2011).

    PubMed  PubMed Central  Google Scholar 

  75. H. H. Tsai, H. H. Liou, C. H. Muo, et al., “Hepatitis C virus infection as a risk factor for Parkinson disease A nationwide cohort study,” Neurology, 86, No. 9, 840–846 (2016).

    PubMed  Google Scholar 

  76. J. Y. Wang, J. Y. Wang, J. Y. Wang, et al., “Ethanol modulates induction of nitric oxide synthase in glial cells by endotoxin,” Life Sci., 63, No. 17, 1571–1583 (1998).

    CAS  PubMed  Google Scholar 

  77. J. M. Woulfe, M. T. Gray, D. A. Gray, et al., “Hypothesis: a role for EBV-induced molecular mimicry in Parkinson’s disease,” Parkinsonism Relat. Disord., 20, No. 7, 685–694 (2014).

    PubMed  Google Scholar 

  78. W. Y. Wu, K. H. Kang, S. S. Chen, et al., “Hepatitis C virus infection: a risk factor for Parkinson’s disease,” J. Viral. Hepat., 22, No. 10, 784–791 (2015).

    CAS  PubMed  Google Scholar 

  79. B. Y. Zeng, S. Bukhatwa, A. Hikima, et al., “Reproducible nigral cell loss after systemic proteasomal inhibitor administration to rats,” Ann. Neurol., 60, No. 2, 248–252 (2006).

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    M. N. Karpenko & I. V. Ekimova

  2. Institute of Experimental Medicine, St. Petersburg, Russia

    M. N. Karpenko, Z. M. Muruzheva & N. S. Pestereva

  3. Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia

    M. N. Karpenko & N. S. Pestereva

  4. St. Petersburg National Research University for Information Technologies, Mechanics, and Optics, St. Petersburg, Russia

    M. N. Karpenko

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  1. M. N. Karpenko
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  2. Z. M. Muruzheva
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  3. N. S. Pestereva
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  4. I. V. Ekimova
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Correspondence to M. N. Karpenko.

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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 103, No. 8, pp. 841–853, August, 2017.

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Karpenko, M.N., Muruzheva, Z.M., Pestereva, N.S. et al. An Infection Hypothesis of Parkinson’s Disease. Neurosci Behav Physi 49, 555–561 (2019). https://doi.org/10.1007/s11055-019-00769-1

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