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Cited by 125Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

Infection and Risk of Parkinson’s Disease

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Smeyne, Richard J., Noyce, Alastair J., Byrne, Matthew, Savica, Rodolfo, Marras, Connie·2021·Journal of Parkinson's Disease
DOI 10.3233/jpd-202279PMC PMC7990414
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Abstract

Parkinson’s disease (PD) is thought to be caused by a combination of genetic and environmental factors. Bacterial or viral infection has been proposed as a potential risk factor, and there is supporting although not entirely consistent epidemiologic and basic science evidence to support its role. Encephalitis caused by influenza has included parkinsonian features. Epidemiological evidence is most compelling for an association between PD and hepatitis C virus. Infection with Helicobacter pylori may be associated not only with PD risk but also response to levodopa. Rapidly evolving knowledge regarding the role of the microbiome also suggests a role of resident bacteria in PD risk. Biological plausibility for the role for infectious agents is supported by the known neurotropic effects of specific viruses, particular vulnerability of the substantia nigra and even the promotion of aggregation of alpha-synuclein. A common feature of implicated viruses appears to be production of high levels of cytokines and chemokines that can cross the blood-brain barrier leading to microglial activation and inflammation and ultimately neuronal cell death. Based on multiple avenues of evidence it appears likely that specific bacterial and particularly viral infections may increase vulnerability to PD. The implications of this for PD prevention requires attention and may be most relevant once preventive treatments for at-risk populations are developed.

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  • Peripheral inflammatory molecules induced by acute systemic viral or bacterial infections can affect brain function through neural and humoral pathways.

    “Multiple clinical and experimental studies have demonstrated that peripheral inflammatory molecules induced by acute systemic viral or bacterial infections can affect brain function through neural and humoral pathways.94,98,99”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [98]

    The Molecular Mechanisms section (page unavailable) says viral and bacterial infections induce circulating inflammatory molecules that can cross the blood–brain barrier and activate microglia, supporting a blood-borne pathway affecting the brain. The passages found do not describe a neural pathway for those molecules, so they do not support that part of the claim. (LLM, conf=0.85)

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  1. [1]Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D, Tan M, Kia DA, Noyce AJ, Xue A, Bras J, Young E, von Coelln R, Simón-Sánchez J, Schulte C, Sharma M, Krohn L, Pihlstrøm L, Siitonen A, Iwaki H, Leonard H, Faghri F, Gibbs JR, Hernandez DG, Scholz SW, Botia JA, Martinez M, Corvol JC, Lesage S, Jankovic J, Shulman LM, Sutherland M, Tienari P, Majamaa K, Toft M, Andreassen OA, Bangale T, Brice A, Yang J, Gan-Or Z, Gasser T, Heutink P, Shulman JM, Wood NW, Hinds DA, Hardy JA, Morris HR, Gratten J, Visscher PM, Graham RR, Singleton AB (2019) Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: A meta-analysis of genome-wide association studies. Lancet Neurol 18, 1091– 1102. 31701892 PMC8422160
  2. [2]Chen H, Ritz B (2018) The search for environmental causes of Parkinson’s disease: Moving forward. J Parkinsons Dis 8, S9– s17. 30584168 PMC6311360
  3. [3]Marras C, Canning CG, Goldman SM (2019) Environment, lifestyle, and Parkinson’s disease: Implications for prevention in the next decade. Mov Disord 34, 801– 811. 31091353
  4. [4]Henry J, Smeyne RJ, Jang H, Miller B, Okun MS (2010) Parkinsonism and neurological manifestations of influenza throughout the 20th and 21st centuries. Parkinsonism Relat Disord 16, 566– 571. 20650672 PMC4684089
  5. [5]Casals J, Elizan TS, Yahr MD (1998) Postencephalitic parkinsonism–a review. J Neural Transm (Vienna) 105, 645– 676. 9826109
  6. [6]Rebai I, Ben Rhouma H, Kraoua I, Klaa H, Rouissi A, Ben Youssef-Turki I, Gouider-Khouja N (2015) Postencephalitic parkinsonism and selective involvement of substantia nigra in childhood. Brain Dev 37, 153– 157. 24745788
  7. [8]Pont-Sunyer C, Hotter A, Gaig C, Seppi K, Compta Y, Katzenschlager R, Mas N, Hofeneder D, Brücke T, Bayés A, Wenzel K, Infante J, Zach H, Pirker W, Posada IJ, Álvarez R, Ispierto L, De Fábregues O, Callén A, Palasí A, Aguilar M, Martí MJ, Valldeoriola F, Salamero M, Poewe W, Tolosa E (2015) The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Mov Disord 30, 229– 237. 25449044
  8. [9]Pradhan S, Andreasson K (2013) Commentary: Progressive inflammation as a contributing factor to early development of Parkinson’s disease. Exp Neurol 241, 148– 155. 23261765
  9. [10]Tsui JK, Calne DB, Wang Y, Schulzer M, Marion SA (1999) Occupational risk factors in Parkinson’s disease. Can J Public Health 90, 334– 337. 10570579 PMC6979620
  10. [11]Patrick KL, Bell SL, Weindel CG, Watson RO (2019) Exploring the “Multiple-Hit Hypothesis” of neurodegenerative disease: Bacterial infection comes up to bat. Front Cell Infect Microbiol 9, 138. 31192157 PMC6546885
  11. [12]Mattson MP (2004) Infectious agents and age-related neurodegenerative disorders. Ageing Res Rev 3, 105– 120. 15163105 PMC7172323
  12. [13]Umemura A, Oeda T, Tomita S, Hayashi R, Kohsaka M, Park K, Sugiyama H, Sawada H (2014) Delirium and high fever are associated with subacute motor deterioration in Parkinson disease: A nested case-control study. PLoS One 9, e94944. 24887491 PMC4041721
  13. [15]McCall S, Henry JM, Reid AH, Taubenberger JK (2001) Influenza RNA not detected in archival brain tissues from acute encephalitis lethargica cases or in postencephalitic Parkinson cases. J Neuropathol Exp Neurol 60, 696– 704. 11444798
  14. [16]Kapila CC, Kaul S, Kapur SC, Kalayanam TS, Banerjee D (1958) Neurological and hepatic disorders associated with influenza. Br Med J 2, 1311– 1314. 13596594 PMC2027345
  15. [18]Sadasivan S, Zanin M, O’Brien K, Schultz-Cherry S, Smeyne RJ (2015) Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus. PLoS One 10, e0124047. 25861024 PMC4393251
  16. [19]Ferrara JL, Abhyankar S, Gilliland DG (1993) Cytokine storm of graft-versus-host disease: A critical effector role for interleukin-1. Transplant Proc 25, 1216– 1217. 8442093
  17. [20]Harry GJ, Kraft AD (2008) Neuroinflammation and microglia: Considerations and approaches for neurotoxicity assessment. Expert Opin Drug Metab Toxicol 4, 1265– 1277. 18798697 PMC2658618
  18. [21]Sulzer D (2007) Multiple hit hypotheses for dopamine neuron loss in Parkinson’s disease. Trends Neurosci 30, 244– 250. 17418429
  19. [22]Jang H, Boltz DA, Webster RG, Smeyne RJ (2009) Viral parkinsonism. Biochim Biophys Acta 1792, 714– 721. 18760350 PMC4642437
  20. [23]Wang H, Liu X, Tan C, Zhou W, Jiang J, Peng W, Zhou X, Mo L, Chen L (2020) Bacterial, viral, and fungal infection-related risk of Parkinson’s disease: Meta-analysis of cohort and case–control studies. Brain Behav 10, e01549. 32017453 PMC7066372
  21. [24]Polidoro RB, Hagan RS, de Santis Santiago R, Schmidt NW (2020) Overview: Systemic inflammatory response derived from lung injury caused by SARS-CoV-2 infection explains severe outcomes in COVID-19. Front Immunol 11, 1626. 32714336 PMC7344249
  22. [26]Forton DM, Allsop JM, Main J, Foster GR, Thomas HC, Taylor-Robinson SD (2001) Evidence for a cerebral effect of the hepatitis C virus. Lancet 358, 38– 39. 11454379
  23. [27]Wilkinson J, Radkowski M, Laskus T (2009) Hepatitis C virus neuroinvasion: Identification of infected cells. J Virol 83, 1312– 1319. 19019968 PMC2620915
  24. [28]Wu WY-Y, Kang K-H, Chen SL-S, Chiu SY-H, Yen AM-F, Fann JC-Y, Su C-W, Liu H-C, Lee C-Z, Fu W-M, Chen H-H, Liou H-H (2015) Hepatitis C virus infection: A risk factor for Parkinson’s disease. J Viral Hepatitis 22, 784– 791. 25608223
  25. [29]Tsai HH, Liou HH, Muo CH, Lee CZ, Yen RF, Kao CH (2016) Hepatitis C virus infection as a risk factor for Parkinson disease: A nationwide cohort study. Neurology 86, 840– 846. 26701382
  26. [30]Pakpoor J, Noyce A, Goldacre R, Selkihova M, Mullin S, Schrag A, Lees A, Goldacre M (2017) Viral hepatitis and Parkinson disease: A national record-linkage study. Neurology 88, 1630– 1633. 28356465
  27. [31]Wijarnpreecha K, Chesdachai S, Jaruvongvanich V, Ungprasert P (2018) Hepatitis C virus infection and risk of Parkinson’s disease: A systematic review and meta-analysis. Eur J Gastroenterol Hepatol 30, 9– 13. 29049127
  28. [32]Goldstein L, Fogel-Grinvald H, Steiner I (2019) Hepatitis B and C virus infection as a risk factor for Parkinson’s disease in Israel-A nationwide cohort study. J Neurol Sci 398, 138– 141. 30710864
  29. [33]Lin W-Y, Lin M-S, Weng Y-H, Yeh T-H, Lin Y-S, Fong P-Y, Wu Y-R, Lu C-S, Chen R-S, Huang Y-Z (2019) Association of antiviral therapy with risk of Parkinson disease in patients with chronic hepatitis C virus infection. JAMA Neurol 76, 1019– 1027. PMC6551582 31168563
  30. [34]Su T-H, Yang H-C, Tseng T-C, Chou S-W, Lin C-H, Liu C-H, Liu C-J, Chen C-L, Kao J-H (2019) Antiviral therapy in patients with chronic hepatitis C is associated with a reduced risk of parkinsonism. Mov Disord 34, 1882– 1890. 31505068
  31. [35]Working Group of the American Academy of Neurology AIDS Task Force (1991) Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Neurology 41, 778– 778. 2046917
  32. [36]Mirsattari SM, Power C, Nath A (1998) Parkinsonism with HIV infection. Mov Disord 13, 684– 689. 9686775
  33. [37]Tisch S, Brew BJ (2010) HIV, HAART, and Parkinson’s disease: Co-incidence or pathogenetic link? Mov Disord 25, 2257– 2258. 20803513
  34. [38]Tse W, Cersosimo MG, Gracies JM, Morgello S, Olanow CW, Koller W (2004) Movement disorders and AIDS: A review. Parkinsonism Relat Disord 10, 323– 334. 15261874
  35. [39]Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: Differences in rates, nature, and predictors. J Neurovirol 17, 3– 16. 21174240 PMC3032197
  36. [40]Siangphoe U, Archer KJ, Nguyen C, Lee KR (2020) Associations of antiretroviral therapy and comorbidities with neurocognitive outcomes in HIV-1-infected patients. AIDS 34, 893– 902. 32028325
  37. [41]Dehner LF, Spitz M, Pereira JS (2016) Parkinsonism in HIV infected patients during antiretroviral therapy - data from a Brazilian tertiary hospital. Braz J Infect Dis 20, 499– 501. 27449286 PMC9425509
  38. [42]Liu B, Gao HM, Hong JS (2003) Parkinson’s disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: Role of neuroinflammation. Environ Health Perspect 111, 1065– 1073. 12826478 PMC1241555
  39. [43]Pische G, Koob M, Wirth T, Quenardelle V, Lagha-Boukbiza O, Renaud M, Anheim M, Tranchant C (2017) Subacute parkinsonism as a complication of Lyme disease. J Neurol 264, 1015– 1019. 28349210
  40. [44]Blum K, Modestino EJ, Febo M, Steinberg B, McLaughlin T, Fried L, Baron D, Siwicki D, Badgaiyan RD (2017) Lyme and dopaminergic function: Hypothesizing reduced reward deficiency symptomatology by regulating dopamine transmission. J Syst Integr Neurosci 3, doi: 10.15761/JSIN.1000163 PMC5521197 28736624 · DOI
  41. [45]Cassarino DS, Quezado MM, Ghatak NR, Duray PH (2003) Lyme-associated parkinsonism: A neuropathologic case study and review of the literature. Arch Pathol Lab Med 127, 1204– 1206. 12946221
  42. [46]Forrester JD, Kugeler KJ, Perea AE, Pastula DM, Mead PS (2015) No geographic correlation between lyme disease and death due to 4 neurodegenerative disorders, United States, 2001-2010. Emerg Infect Dis 21, 2036– 2039. 26488307 PMC4622257
  43. [47]Haahr R, Tetens MM, Dessau RB, Krogfelt KA, Bodilsen J, Andersen NS, Moller JK, Roed C, Christiansen CB, Ellermann-Eriksen S, Bangsborg JM, Hansen K, Benfield TL, Ostergaard Andersen C, Obel N, Lebech AM, Omland LH (2019) Risk of neurological disorders in patients with European Lyme neuroborreliosis. A nationwide population-based cohort study. Clin Infect Dis 71, 1511– 1516. 31598647
  44. [48]McGee DJ, Lu XH, Disbrow EA (2018) Stomaching the possibility of a pathogenic role for Helicobacter pylori in Parkinson’s disease. J Parkinsons Dis 8, 367– 374. 29966206 PMC6130334
  45. [49]Schwab RS (1961) Symptomatology and medical treatment of Parkinson’s disease. Int J Neurol 2, 61– 75. 13909634
  46. [51]Shen X, Yang H, Wu Y, Zhang D, Jiang H (2017) Meta-analysis: Association of Helicobacter pylori infection with Parkinson’s diseases. Helicobacter 22, e12398. 28598012
  47. [52]Huang HK, Wang JH, Lei WY, Chen CL, Chang CY, Liou LS (2018) Helicobacter pylori infection is associated with an increased risk of Parkinson’s disease: A population-based retrospective cohort study. Parkinsonism Relat Disord 47, 26– 31. 29174171
  48. [53]Tan AH, Mahadeva S, Marras C, Thalha AM, Kiew CK, Yeat CM, Ng SW, Ang SP, Chow SK, Loke MF, Vadivelu JS, Ibrahim N, Yong HS, Tan CT, Fox SH, Lang AE, Lim SY (2015) Helicobacter pylori infection is associated with worse severity of Parkinson’s disease. Parkinsonism Relat Disord 21, 221– 225. 25560322
  49. [54]Rahne KE, Tagesson C, Nyholm D (2013) Motor fluctuations and Helicobacter pylori in Parkinson’s disease. J Neurol 260, 2974– 2980. 24002418
  50. [55]Kohbata S, Beaman BL (1991) L-dopa-responsive movement disorder caused by Nocardia asteroides localized in the brains of mice. Infect Immun 59, 181– 191. 1670928 PMC257724
  51. [56]Tam S, Barry DP, Beaman L, Beaman BL (2002) Neuroinvasive Nocardia asteroides GUH-2 induces apoptosis in the substantia nigra in vivo and dopaminergic cells in vitro. Exp Neurol 177, 453– 460. 12429191
  52. [57]Kohbata S, Shimokawa K (1993) Circulating antibody to Nocardia in the serum of patients with Parkinson’s disease. Adv Neurol 60, 355– 357. 8420152
  53. [58]Elkind MS, Ramakrishnan P, Moon YP, Boden-Albala B, Liu KM, Spitalnik SL, Rundek T, Sacco RL, Paik MC (2010) Infectious burden and risk of stroke: The northern Manhattan study. Arch Neurol 67, 33– 38. 19901154 PMC2830860
  54. [59]Bu XL, Yao XQ, Jiao SS, Zeng F, Liu YH, Xiang Y, Liang CR, Wang QH, Wang X, Cao HY, Yi X, Deng B, Liu CH, Xu J, Zhang LL, Gao CY, Xu ZQ, Zhang M, Wang L, Tan XL, Xu X, Zhou HD, Wang YJ (2015) A study on the association between infectious burden and Alzheimer’s disease. Eur J Neurol 22, 1519– 1525. 24910016
  55. [60]Hasan S, Mielke MM, Ahlskog JE, Bower J, Turcano P, Savica R (2020) Infections or sepsis preceding clinically diagnosed α-synucleinopathies: A case-control study. Mov Disord 35, 1684– 1689. 32479692 PMC7818650
  56. [61]Bhattacharyya D, Mohite GM, Krishnamoorthy J, Gayen N, Mehra S, Navalkar A, Kotler SA, Ratha BN, Ghosh A, Kumar R, Garai K, Mandal AK, Maji SK, Bhunia A (2019) Lipopolysaccharide from Gut Microbiota Modulates alpha-Synuclein Aggregation and Alters Its Biological Function. ACS Chem Neurosci 10, 2229– 2236. 30855940
  57. [64]Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T, Mujagic Z, Vila AV, Falony G, Vieira-Silva S, Wang J, Imhann F, Brandsma E, Jankipersadsing SA, Joossens M, Cenit MC, Deelen P, Swertz MA, LifeLines cohort study, Weersma RK, Feskens EJ, Netea MG, Gevers D, Jonkers D, Franke L, Aulchenko YS, Huttenhower C, Raes J, Hofker MH, Xavier RJ, Wijmenga C, Fu J (2016) Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565– 569. 27126040 PMC5240844
  58. [65]Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK (2016) Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167, 1469– 1480 e1412. 27912057 PMC5718049
  59. [67]Hasegawa S, Goto S, Tsuji H, Okuno T, Asahara T, Nomoto K, Shibata A, Fujisawa Y, Minato T, Okamoto A, Ohno K, Hirayama M (2015) Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson’s disease. PLoS One 10, e0142164. 26539989 PMC4634857
  60. [68]Killinger BA, Madaj Z, Sikora JW, Rey N, Haas AJ, Vepa Y, Lindqvist D, Chen H, Thomas PM, Brundin P, Brundin L, Labrie V (2018) The vermiform appendix impacts the risk of developing Parkinson’s disease. Sci Transl Med 10, eaar5280. 30381408 PMC6319259
  61. [69]Marras C, Lang AE, Austin PC, Lau C, Urbach DR (2016) Appendectomy in mid and later life and risk of Parkinson’s disease: A population-based study. Mov Disord 31, 1243– 1247. 27241338
  62. [70]Svensson E, Horváth-Puhó E, Stokholm MG, Sørensen HT, Henderson VW, Borghammer P (2016) Appendectomy and risk of Parkinson’s disease: A nationwide cohort study with more than 10 years of follow-up. Mov Disord 31, 1918– 1922. 27621223
  63. [71]Schultz DR, Barthal JS, Garrett G (1977) Western equine encephalitis with rapid onset of parkinsonism. Neurology 27, 1095– 1096. 563006
  64. [72]Bantle CM, Phillips AT, Smeyne RJ, Rocha SM, Olson KE, Tjalkens RB (2019) Infection with mosquito-borne alphavirus induces selective loss of dopaminergic neurons, neuroinflammation and widespread protein aggregation. NPJ Parkinsons Dis 5, 20. 31531390 PMC6744428
  65. [73]Jang H, Boltz D, McClaren J, Pani AK, Smeyne M, Korff A, Webster R, Smeyne RJ (2012) Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice. J Neurosci 32, 1545– 1559. 22302798 PMC3307392
  66. [74]Jang H, Boltz D, Sturm-Ramirez K, Shepherd KR, Jiao Y, Webster R, Smeyne RJ (2009) Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration. Proc Natl Acad Sci U S A 106, 14063– 14068. 19667183 PMC2729020
  67. [75]Phillips AT, Stauft CB, Aboellail TA, Toth AM, Jarvis DL, Powers AM, Olson KE (2013) Bioluminescent imaging and histopathologic characterization of WEEV neuroinvasion in outbred CD-1 mice. PLoS One 8, e53462. 23301074 PMC3534643
  68. [76]Marreiros R, Müller-Schiffmann A, Trossbach SV, Prikulis I, Hänsch S, Weidtkamp-Peters S, Moreira AR, Sahu S, Soloviev I, Selvarajah S, Lingappa VR, Korth C (2020) Disruption of cellular proteostasis by H1N1 influenza A virus causes α-synuclein aggregation. Proc Natl Acad Sci U S A 117, 6741– 6751. 32152117 PMC7104400
  69. [79]Banks WA, Kastin AJ, Broadwell RD (1995) Passage of cytokines across the blood-brain barrier. Neuroimmunomodulation 2, 241– 248. 8963753
  70. [80]Basler CF (2017) Molecular pathogenesis of viral hemorrhagic fever. Semin Immunopathol 39, 551– 561. 28555386 PMC6436832
  71. [81]Steinberg BE, Goldenberg NM, Lee WL (2012) Do viral infections mimic bacterial sepsis? The role of microvascular permeability: A review of mechanisms and methods. Antiviral Res 93, 2– 15. 22068147
  72. [83]Benveniste EN, Benos DJ (1995) TNF-alpha- and IFN-gamma-mediated signal transduction pathways: Effects on glial cell gene expression and function. FASEB J 9, 1577– 1584. 8529837
  73. [84]Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S (2009) Infiltration of CD4+lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 119, 182– 192. 19104149 PMC2613467
  74. [85]McGeer PL, Itagaki S, Akiyama H, McGeer EG (1988) Rate of cell death in parkinsonism indicates active neuropathological process. Ann Neurol 24, 574– 576. 3239957
  75. [86]Ip CW, Beck SK, Volkmann J (2015) Lymphocytes reduce nigrostriatal deficits in the 6-hydroxydopamine mouse model of Parkinson’s disease. J Neural Transm (Vienna) 122, 1633– 1643. 26290125
  76. [87]Dutta D, Kundu M, Mondal S, Roy A, Ruehl S, Hall DA, Pahan K (2019) RANTES-induced invasion of Th17 cells into substantia nigra potentiates dopaminergic cell loss in MPTP mouse model of Parkinson’s disease. Neurobiol Dis 132, 104575. 31445159 PMC6834904
  77. [88]Subbarayan MS, Hudson C, Moss LD, Nash KR, Bickford PC (2020) T cell infiltration and upregulation of MHCII in microglia leads to accelerated neuronal loss in an α-synuclein rat model of Parkinson’s disease. J Neuroinflammation 17, 242. 32799878 PMC7429710
  78. [89]Jimenez-Ferrer I, Swanberg M (2018) Immunogenetics of Parkinson’s disease. In Parkinson’s Disease: Pathogenesis and Clinical Aspects, Stoker TB, Greenland JC, eds. Codon Publications, Brisbane. 30702835
  79. [90]Harms AS, Cao S, Rowse AL, Thome AD, Li X, Mangieri LR, Cron RQ, Shacka JJ, Raman C, Standaert DG (2013) MHCII is required for alpha-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. J Neurosci 33, 9592– 9600. 23739956 PMC3903980
  80. [91]Sulzer D, Alcalay RN, Garretti F, Cote L, Kanter E, Agin-Liebes J, Liong C, McMurtrey C, Hildebrand WH, Mao X, Dawson VL, Dawson TM, Oseroff C, Pham J, Sidney J, Dillon MB, Carpenter C, Weiskopf D, Phillips E, Mallal S, Peters B, Frazier A, Lindestam Arlehamn CS, Sette A (2017) T cells from patients with Parkinson’s disease recognize alpha-synuclein peptides. Nature 546, 656– 661. 28636593 PMC5626019
  81. [92]Kim WG, Mohney RP, Wilson B, Jeohn GH, Liu B, Hong JS (2000) Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: Role of microglia. J Neurosci 20, 6309– 6316. 10934283 PMC6772569
  82. [93]Smeyne M, Jiao Y, Shepherd KR, Smeyne RJ (2005) Glia cell number modulates sensitivity to MPTP in mice. Glia 52, 144– 152. 15920722
  83. [94]Barcia C, Ros CM, Annese V, Gómez A, Ros-Bernal F, Aguado-Yera D, Martínez-Pagán ME, de Pablos V, Fernandez-Villalba E, Herrero MT (2011) IFN-γ signaling, with the synergistic contribution of TNF-α, mediates cell specific microglial and astroglial activation in experimental models of Parkinson’s disease. Cell Death Dis 2, e142. 21472005 PMC3122054
  84. [95]Tansey MG, Goldberg MS (2010) Neuroinflammation in Parkinson’s disease: Its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis 37, 510– 518. 19913097 PMC2823829
  85. [96]Tansey MG, McCoy MK, Frank-Cannon TC (2007) Neuroinflammatory mechanisms in Parkinson’s disease: Potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 208, 1– 25. 17720159 PMC3707134
  86. [97]Rothwell NJ (1999) Annual review prize lecture cytokines - killers in the brain? J Physiol 514(Pt 1), 3– 17. 9831712 PMC2269053
  87. [98]Hayes GM, Woodroofe MN, Cuzner ML (1988) Microglia express MHC class II in normal and demyelinating human white matter. Ann N Y Acad Sci 540, 501– 503. 3061347
  88. [99]Hayes GM, Woodroofe MN, Cuzner ML (1987) Microglia are the major cell type expressing MHC class II in human white matter. J Neurol Sci 80, 25– 37. 3302117
  89. [100]Rostami J, Fotaki G, Sirois J, Mzezewa R, Bergström J, Essand M, Healy L, Erlandsson A (2020) Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson’s disease brain. J Neuroinflammation 17, 119. 32299492 PMC7164247
  90. [102]Yao YY, Ling EA, Lu D (2020) Microglia mediated neuroinflammation - signaling regulation and therapeutic considerations with special reference to some natural compounds. Histol Histopathol, doi: 10.14670/HH-18-239. 32662061 · DOI
  91. [103]Beatman EL, Massey A, Shives KD, Burrack KS, Chamanian M, Morrison TE, Beckham JD (2015) Alpha-synuclein expression restricts RNA viral infections in the brain. J Virol 90, 2767– 2782. 26719256 PMC4810656
  92. [104]Stolzenberg E, Berry D, Yang D, Lee EY, Kroemer A, Kaufman S, Wong GCL, Oppenheim JJ, Sen S, Fishbein T, Bax A, Harris B, Barbut D, Zasloff MA (2017) A role for neuronal alpha-synuclein in gastrointestinal immunity. J Innate Immun 9, 456– 463. 28651250 PMC5865636
  93. [105]Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, Lee JH, Kim WR, Kook M, Foss CA, Shen C, Lee H, Kulkarni S, Pasricha PJ, Lee G, Pomper MG, Dawson VL, Dawson TM, Ko HS (2019) Transneuronal propagation of pathologic α-synuclein from the gut to the brain models Parkinson’s disease. Neuron 103, 627– 641.e627. 31255487 PMC6706297
  94. [106]Braak H, Rüb U, Gai WP, Del Tredici K (2003) Idiopathic Parkinson’s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna) 110, 517– 536. 12721813
  95. [107]Acosta SA, Tajiri N, de la Pena I, Bastawrous M, Sanberg PR, Kaneko Y, Borlongan CV (2015) Alpha-synuclein as a pathological link between chronic traumatic brain injury and Parkinson’s disease. J Cell Physiol 230, 1024– 1032. 25251017 PMC4328145
  96. [108]Costa LG, Cole TB, Dao K, Chang YC, Coburn J, Garrick JM (2020) Effects of air pollution on the nervous system and its possible role in neurodevelopmental and neurodegenerative disorders. Pharmacol Ther 210, 107523. 32165138 PMC7245732
  97. [109]De Miranda BR, Greenamyre JT (2020) Trichloroethylene, a ubiquitous environmental contaminant in the risk for Parkinson’s disease. Environ Sci Process Impacts 22, 543– 554. 31996877 PMC7941732
  98. [110]Kanthasamy A, Jin H, Charli A, Vellareddy A, Kanthasamy A (2019) Environmental neurotoxicant-induced dopaminergic neurodegeneration: A potential link to impaired neuroinflammatory mechanisms. Pharmacol Ther 197, 61– 82. 30677475 PMC6520143

Cited by

Sorted by citations

Authors
Smeyne, R. J., Noyce, A. J., Byrne, M., Savica, R., & Marras, C.
Affiliations
  • Thomas Jefferson University (US)
  • Queen Mary University of London (GB)
  • Mayo Clinic (US)
  • University of Toronto (CA)
Corresponding author
Marras, Connie
ORCID
Venue
Journal of Parkinson's Disease
Publisher
SAGE Publications
Published
2021-02-02
Volume
11
Issue
1
Pages
31-43
ISSN
  • 1877-7171 (ISSN-L)
  • 1877-718X
DOI
10.3233/jpd-202279
PMC
PMC7990414
OpenAlex
W3117517717
Cited by
125
References
11
Citations by year
2026: 13 · 2025: 26 · 2024: 37 · 2023: 17 · 2022: 28 · 2021: 4
FWCI
1.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Parkinson s Disease (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • The Medicine Forum (submittedVersion, cc-by-nc)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
Funders
  • Michael J. Fox Foundation for Parkinson's Research
  • Mayo Clinic
  • Biogen
  • F. Hoffmann-La Roche
  • Parkinson's Foundation
  • ACADIA Pharmaceuticals
  • Barts Charity (MGU0364)
  • Parkinson's UK
  • Canadian Institutes of Health Research
  • National Institute on Aging
  • National Institute of Neurological Disorders and Stroke
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, infection as risk factor, viral infection, bacterial infection, hepatitis C virus, influenza encephalitis, Helicobacter pylori, levodopa response, gut microbiota, alpha-synuclein aggregation, substantia nigra, neuroinflammation, microglial activation, cytokines, blood-brain barrier, neurodegeneration, Parkinson's disease prevention
MeSH terms
Gastrointestinal Microbiome, Bacterial Infections, Humans, Parkinson Disease, Virus Diseases

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