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Cited by 38Extracellular vesicles in diseaseParkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration Mechanisms

Glia-derived extracellular vesicles in parkinson’s disease.

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Marchetti, Bianca, Leggio, Loredana, L’Episcopo, Francesca, Vivarelli, Silvia, Tirolo, Cataldo, Paternò, Greta, Giachino, Carmela, Caniglia, Salvatore +2 more·2020·Journal of Clinical Medicine
DOI 10.3390/jcm9061941PMC PMC7356371
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Abstract

Glial cells are fundamental players in the central nervous system (CNS) development and homeostasis, both in health and disease states. In Parkinson’s disease (PD), a dysfunctional glia-neuron crosstalk represents a common final pathway contributing to the chronic and progressive death of dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc). Notably, glial cells communicating with each other by an array of molecules, can acquire a “beneficial” or “destructive” phenotype, thereby enhancing neuronal death/vulnerability and/or exerting critical neuroprotective and neuroreparative functions, with mechanisms that are actively investigated. An important way of delivering messenger molecules within this glia-neuron cross-talk consists in the secretion of extracellular vesicles (EVs). EVs are nano-sized membranous particles able to convey a wide range of molecular cargoes in a controlled way, depending on the specific donor cell and the microenvironmental milieu. Given the dual role of glia in PD, glia-derived EVs may deliver molecules carrying various messages for the vulnerable/dysfunctional DAergic neurons. Here, we summarize the state-of-the-art of glial-neuron interactions and glia-derived EVs in PD. Also, EVs have the ability to cross the blood brain barrier (BBB), thus acting both within the CNS and outside, in the periphery. In these regards, this review discloses the emerging applications of EVs, with a special focus on glia-derived EVs as potential carriers of new biomarkers and nanotherapeutics for PD.

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  • In Alzheimer's and Parkinson's diseases, astrocytes increase release of AEVs containing molecules that inhibit neurotoxic effects of plaques but also induce apoptosis on neurons.

    “For instance, in AD and PD, astrocytes try to balance the excessive production of amyloids, by increasing the release of AEVs containing molecules that are supposed to inhibit the neurotoxic effects of the plaques, but also induce apoptosis on neurons (Leggio et al., 2021; Marchetti et al., 2020).”

    From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Marchetti et al., 2020

    Section 4.3 reports that astrocyte-derived EVs can carry molecules that protect neurons, while Section 3.2 describes astrocyte-derived EVs with potentially harmful cargo. The paper does not say that astrocytes increase AEV release to counter amyloid plaques in AD and PD, or that those protective AEVs also induce neuronal apoptosis; the apoptosis example in Section 3.2 concerns microglial EVs. (LLM, conf=0.84)

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  • The presence of EV markers, mitochondrial, Golgi, and ER components within varicosities indicates potential roles in cellular communication, metabolic stress management, and intercellular signaling under pathological or inflammatory conditions.

    “indicating potential roles in cellular communication, metabolic stress management, and intercellular signaling under pathological or inflammatory conditions, as previously reported for reactive astrocytes (26, 42, 43).”

    From Varicose projection astrocytes: Conserved reactive cells in brain pathology (2026) · cites this paper as [42]

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References 205 · Cited by 38

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  1. [1]Barres B.A. The Mystery and Magic of Glia: A Perspective on Their Roles in Health and Disease Neuron 2008 60 430 440 10.1016/j.neuron.2008.10.013 18995817 · DOI · Paper page
  2. [2]Bélanger M. Magistretti P.J. The role of astroglia in neuroprotection Dialogues Clin. Neurosci. 2009 11 281 295 19877496 PMC3181926
  3. [3]Sofroniew M.V. Vinters H.V. Astrocytes: Biology and pathology Acta Neuropathol. 2010 119 7 35 10.1007/s00401-009-0619-8 20012068 PMC2799634 · DOI · Paper page
  4. [4]Gallo F. Morale M.C. Avola R. Marchetti B. Cross-talk between luteinizing hormone-releasing hormone (LHRH) neurons and astroglial cells: Developing glia release factors that accelerate neuronal differentiation and stimulate LHRH release from GT(1-1) neuronal cell line and LHRH neurons induce astroglia proliferation Endocrine 1995 3 863 874 10.1007/BF02738891 21153214 · DOI
  5. [5]Marchetti B. Cross-talk signals in the CNS Role of neurotrophic and hormonal factors adhesion molecules and intercellular signaling agents in luteinizing hormone-releasing hormone LHRH -astroglial interactive network Front. Biosci. 1997 2 A177 10.2741/A177 9159216 · DOI
  6. [6]Gallo F. Morale M.C. Spina-Purrello V. Tirolo C. Testa N. Farinella Z. Avola R. Beaudet A. Marchetti B. Basic fibroblast growth factor (bFGF) acts on both neurons and glia to mediate the neurotrophic effects of astrocytes on LHRH neurons in culture Synapse 2000 36 233 253 10.1002/(SICI)1098-2396(20000615)36:4<233::AID-SYN1>3.0.CO;2-I 10819902 · DOI
  7. [7]Gennuso F. Fernetti C. Tirolo C. Testa N. L’Episcopo F. Caniglia S. Morale M.C. Ostrow J.D. Pascolo L. Tiribelli C. Bilirubin protects astrocytes from its own toxicity by inducing up-regulation and translocation of multidrug resistance-associated protein 1 (Mrp1) Proc. Natl. Acad. Sci. USA 2004 101 2470 2475 10.1073/pnas.0308452100 14983033 PMC356974 · DOI
  8. [9]L’Episcopo F. Tirolo C. Testa N. Caniglia S. Concetta Morale M. Marchetti B. Glia as a Turning Point in the Therapeutic Strategy of Parkinsons Disease CNS Neurol. Disord. Drug Targets 2010 9 349 372 10.2174/187152710791292639 20438439 · DOI
  9. [11]Molofsky A.V. Krencik R. Krenick R. Ullian E.M. Ullian E. Tsai H. Deneen B. Richardson W.D. Barres B.A. Rowitch D.H. Astrocytes and disease: A neurodevelopmental perspective Genes Dev. 2012 26 891 907 10.1101/gad.188326.112 22549954 PMC3347787 · DOI · Paper page
  10. [12]Sun D. Jakobs T.C. Structural Remodeling of Astrocytes in the Injured CNS Neuroscience 2012 18 567 588 10.1177/1073858411423441 21982954 PMC3713769 · DOI
  11. [13]Kreutzberg G.W. Microglia: A sensor for pathological events in the CNS Trends Neurosci. 1996 19 312 318 10.1016/0166-2236(96)10049-7 8843599 · DOI · Paper page
  12. [14]Michell-Robinson M.A. Touil H. Healy L.M. Owen D.R. Durafourt B.A. Bar-Or A. Antel J.P. Moore C.S. Roles of microglia in brain development, tissue maintenance and repair Brain 2015 138 1138 1159 10.1093/brain/awv066 25823474 PMC5963417 · DOI
  13. [15]Colonna M. Butovsky O. Microglia Function in the Central Nervous System During Health and Neurodegeneration Annu. Rev. Immunol. 2017 35 441 468 10.1146/annurev-immunol-051116-052358 28226226 PMC8167938 · DOI · Paper page
  14. [16]Davalos D. Grutzendler J. Yang G. Kim J.V. Zuo Y. Jung S. Littman D.R. Dustin M.L. Gan W.-B. ATP mediates rapid microglial response to local brain injury in vivo Nat. Neurosci. 2005 8 752 758 10.1038/nn1472 15895084 · DOI · Paper page
  15. [17]Nimmerjahn A. Kirchhoff F. Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo Science 2005 308 1314 1318 10.1126/science.1110647 15831717 · DOI · Paper page
  16. [18]Cătălin B. Cupido A. Iancău M. Albu C.V. Kirchhoff F. Microglia: First responders in the central nervous system Rom. J. Morphol. Embryol. 2013 54 467 472 24068392
  17. [20]Hirsch L. Jette N. Frolkis A. Steeves T. Pringsheim T. The Incidence of Parkinson’s Disease: A Systematic Review and Meta-Analysis Neuroepidemiology 2016 46 292 300 10.1159/000445751 27105081 · DOI
  18. [21]Poewe W. Seppi K. Tanner C.M. Halliday G.M. Brundin P. Volkmann J. Schrag A.-E. Lang A.E. Parkinson disease Nat. Rev. Dis. Prim. 2017 3 17013 10.1038/nrdp.2017.13 28332488 · DOI · Paper page
  19. [22]Emamzadeh F.N. Surguchov A. Parkinson’s Disease: Biomarkers, Treatment, and Risk Factors Front. Neurosci. 2018 12 10.3389/fnins.2018.00612 30214392 PMC6125353 · DOI
  20. [23]Schapira A.H.V. Olanow C.W. Greenamyre J.T. Bezard E. Slowing of neurodegeneration in Parkinson’s disease and Huntington’s disease: Future therapeutic perspectives Lancet 2014 384 545 555 10.1016/S0140-6736(14)61010-2 24954676 · DOI
  21. [24]Jankovic J. Pathogenesis-targeted therapeutic strategies in Parkinson’s disease Mov. Disord. 2019 34 41 44 10.1002/mds.27534 30484897 · DOI
  22. [25]Surgucheva I. Newell K.L. Burns J. Surguchov A. New α- and γ-synuclein immunopathological lesions in human brain Acta Neuropathol. Commun. 2014 2 132 10.1186/s40478-014-0132-8 25209836 PMC4172890 · DOI
  23. [26]Morale M.C. Serra P.A. Delogu M.R. Migheli R. Rocchitta G. Tirolo C. Caniglia S. Testa N. L’Episcopo F. Gennuso F. Glucocorticoid receptor deficiency increases vulnerability of the nigrostriatal dopaminergic system: Critical role of glial nitric oxide FASEB J. 2004 18 164 166 10.1096/fj.03-0501fje 14630699 · DOI
  24. [27]Langston J.W. The MPTP Story J. Parkinsons Dis. 2017 7 S11 S19 10.3233/JPD-179006 28282815 PMC5345642 · DOI
  25. [28]Collier T.J. Sortwell C.E. Mercado N.M. Steece-Collier K. Cell therapy for Parkinson’s disease: Why it doesn’t work every time Mov. Disord. 2019 34 1120 1127 10.1002/mds.27742 31234239 PMC6771700 · DOI
  26. [29]L’Episcopo F. Tirolo C. Serapide M.F. Caniglia S. Testa N. Leggio L. Vivarelli S. Iraci N. Pluchino S. Marchetti B. Microglia Polarization, Gene-Environment Interactions and Wnt/β-Catenin Signaling: Emerging Roles of Glia-Neuron and Glia-Stem/Neuroprogenitor Crosstalk for Dopaminergic Neurorestoration in Aged Parkinsonian Brain Front. Aging Neurosci. 2018 10 12 10.3389/fnagi.2018.00012 29483868 PMC5816064 · DOI
  27. [30]Blauwendraat C. Heilbron K. Vallerga C.L. Bandres-Ciga S. von Coelln R. Pihlstrøm L. Simón-Sánchez J. Schulte C. Sharma M. Krohn L. Parkinson’s disease age at onset genome-wide association study: Defining heritability, genetic loci, and α-synuclein mechanisms Mov. Disord. 2019 34 866 875 10.1002/mds.27659 30957308 PMC6579628 · DOI
  28. [31]Betarbet R. Canet-Aviles R.M. Sherer T.B. Mastroberardino P.G. McLendon C. Kim J.-H. Lund S. Na H.-M. Taylor G. Bence N.F. Intersecting pathways to neurodegeneration in Parkinson’s disease: Effects of the pesticide rotenone on DJ-1, α-synuclein, and the ubiquitin–proteasome system Neurobiol. Dis. 2006 22 404 420 10.1016/j.nbd.2005.12.003 16439141 · DOI
  29. [32]Edwards T.M. Myers J.P. Environmental Exposures and Gene Regulation in Disease Etiology Environ. Health Perspect. 2007 115 1264 1270 10.1289/ehp.9951 17805414 PMC1964917 · DOI
  30. [33]Cannon J.R. Greenamyre J.T. Gene-environment interactions in Parkinson’s disease: Specific evidence in humans and mammalian models Neurobiol. Dis. 2013 57 38 46 10.1016/j.nbd.2012.06.025 22776331 PMC3815566 · DOI
  31. [34]Hirsch E.C. Jenner P. Przedborski S. Pathogenesis of Parkinson’s disease Mov. Disord. 2013 28 24 30 10.1002/mds.25032 22927094 · DOI · Paper page
  32. [36]Liu H.F. Ho P.W.L. Leung G.C.T. Lam C.S.C. Pang S.Y.Y. Li L. Kung M.H.W. Ramsden D.B. Ho S.L. Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson’s disease Sci. Rep. 2017 7 40087 10.1038/srep40887 28098219 PMC5241661 · DOI
  33. [37]McGeer P.L. Itagaki S. Boyes B.E. McGeer E.G. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains Neurology 1988 38 1285 10.1212/WNL.38.8.1285 3399080 · DOI · Paper page
  34. [38]Marchetti B. Kettenmann H. Streit W.J. Glia-neuron crosstalk in neuroninflammation, neurodegeneration and neuroprotection: Introductory comments: Bianca Marchetti, Helmut Kettenmann and Wolfgang J. Streit Brain Res. Rev. 2005 48 129 132 10.1016/j.brainresrev.2004.12.002 15850651 · DOI
  35. [39]Marchetti B. Serra P.A. Tirolo C. L’Episcopo F. Caniglia S. Gennuso F. Testa N. Miele E. Desole S. Barden N. Glucocorticoid receptor–nitric oxide crosstalk and vulnerability to experimental parkinsonism: Pivotal role for glia–neuron interactions Brain Res. Rev. 2005 48 302 321 10.1016/j.brainresrev.2004.12.030 15850669 · DOI
  36. [42]Gao H.-M. Hong J.-S. Gene–environment interactions: Key to unraveling the mystery of Parkinson’s disease Prog. Neurobiol. 2011 94 1 19 10.1016/j.pneurobio.2011.03.005 21439347 PMC3098527 · DOI
  37. [44]Hirsch E.C. Hunot S. Neuroinflammation in Parkinson’s disease: A target for neuroprotection? Lancet Neurol. 2009 8 382 397 10.1016/S1474-4422(09)70062-6 19296921 · DOI · Paper page
  38. [45]Przedborski S. Inflammation and Parkinson’s disease pathogenesis Mov. Disord. 2010 25 S55 S57 10.1002/mds.22638 20187228 · DOI
  39. [46]Whitton P.S. Neuroinflammation and the prospects for anti-inflammatory treatment of Parkinson’s disease Curr. Opin. Investig. Drugs 2010 11 788 794 20571974
  40. [47]L’Episcopo F. Tirolo C. Caniglia S. Testa N. Serra P.A. Impagnatiello F. Morale M.C. Marchetti B. Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease J. Neuroinflamm. 2010 7 83 10.1186/1742-2094-7-83 PMC3000390 21092260 · DOI
  41. [48]L’Episcopo F. Tirolo C. Testa N. Caniglia S. Morale M.C. Cossetti C. D’Adamo P. Zardini E. Andreoni L. Ihekwaba A.E. Reactive astrocytes and Wnt/β-catenin signaling link nigrostriatal injury to repair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease Neurobiol. Dis. 2011 41 508 527 10.1016/j.nbd.2010.10.023 21056667 PMC3558878 · DOI
  42. [49]L’Episcopo F. Tirolo C. Testa N. Caniglia S. Morale M.C. Impagnatiello F. Marchetti B. Switching the microglial harmful phenotype promotes lifelong restoration of subtantia nigra dopaminergic neurons from inflammatory neurodegeneration in aged mice Rejuvenation Res. 2011 14 411 424 10.1089/rej.2010.1134 21793734 · DOI
  43. [50]L’Episcopo F. Serapide M.F. Tirolo C. Testa N. Caniglia S. Morale M.C. Pluchino S. Marchetti B. A Wnt1 regulated Frizzled-1/β-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection Mol. Neurodegener. 2011 6 49 10.1186/1750-1326-6-49 21752258 PMC3162575 · DOI
  44. [51]Barcia C. Guillemin G.J. Curtin J.F. Zirger J.M. Editorial: Glial Cells: Managers of Neuro-Immunity Front. Cell. Neurosci. 2016 10 10.3389/fncel.2016.00060 27047335 PMC4803723 · DOI
  45. [52]Duffy M.F. Collier T.J. Patterson J.R. Kemp C.J. Luk K.C. Tansey M.G. Paumier K.L. Kanaan N.M. Fischer L.D. Polinski N.K. Lewy body-like alpha-synuclein inclusions trigger reactive microgliosis prior to nigral degeneration J. Neuroinflamm. 2018 15 129 10.1186/s12974-018-1171-z PMC5930695 29716614 · DOI · Paper page
  46. [53]Tansey M.G. Romero-Ramos M. Immune system responses in Parkinson’s disease: Early and dynamic Eur. J. Neurosci. 2019 ejn.14290 10.1111/ejn.14290 PMC6391192 30474172 · DOI
  47. [54]Langston J. Ballard P. Tetrud J. Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis Science 1983 219 979 980 10.1126/science.6823561 6823561 · DOI · Paper page
  48. [55]Langston J.W. Forno L.S. Tetrud J. Reeves A.G. Kaplan J.A. Karluk D. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure Ann. Neurol. 1999 46 598 605 10.1002/1531-8249(199910)46:4<598::AID-ANA7>3.0.CO;2-F 10514096 · DOI · Paper page
  49. [56]Gao H.-M. Liu B. Zhang W. Hong J.-S. Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease FASEB J. 2003 17 1 22 10.1096/fj.03-0109fje 12897068 · DOI
  50. [57]McGeer P.L. McGeer E.G. Inflammation and neurodegeneration in Parkinson’s disease Parkinsonism Relat. Disord. 2004 10 S3 S7 10.1016/j.parkreldis.2004.01.005 15109580 · DOI
  51. [58]Whitton P.S. Inflammation as a causative factor in the aetiology of Parkinson’s disease Br. J. Pharmacol. 2009 150 963 976 10.1038/sj.bjp.0707167 PMC2013918 17339843 · DOI
  52. [59]Hu X. Zhang D. Pang H. Caudle W.M. Li Y. Gao H. Liu Y. Qian L. Wilson B. Di Monte D.A. Macrophage Antigen Complex-1 Mediates Reactive Microgliosis and Progressive Dopaminergic Neurodegeneration in the MPTP Model of Parkinson’s Disease J. Immunol. 2008 181 7194 7204 10.4049/jimmunol.181.10.7194 18981141 PMC2759089 · DOI
  53. [60]Sanchez-Guajardo V. Barnum C.J. Tansey M.G. Romero-Ramos M. Neuroimmunological Processes in Parkinson’s Disease and their Relation to α-Synuclein: Microglia as the Referee between Neuronal Processes and Peripheral Immunity ASN Neuro 2013 5 AN20120066 10.1042/AN20120066 PMC3639751 23506036 · DOI
  54. [61]Marchetti B. L’Episcopo F. Morale M.C. Tirolo C. Testa N. Caniglia S. Serapide M.F. Pluchino S. Uncovering novel actors in astrocyte-neuron crosstalk in Parkinson’s disease: The Wnt/β-catenin signaling cascade as the common final pathway for neuroprotection and self-repair Eur. J. Neurosci. 2013 37 1550 1563 10.1111/ejn.12166 23461676 PMC3660182 · DOI
  55. [62]Schiess M. Nonsteroidal Anti-inflammatory Drugs Protect Against Parkinson Neurodegeneration Arch. Neurol. 2003 60 1043 10.1001/archneur.60.8.1043 12925357 · DOI
  56. [63]Chen H. Jacobs E. Schwarzschild M.A. McCullough M.L. Calle E.E. Thun M.J. Ascherio A. Nonsteroidal antiinflammatory drug use and the risk for Parkinson’s disease Ann. Neurol. 2005 58 963 967 10.1002/ana.20682 16240369 · DOI
  57. [64]Marchetti B. Tirolo C. L’Episcopo F. Caniglia S. Testa N. Smith J.A. Pluchino S. Serapide M.F. Parkinson’s disease, aging and adult neurogenesis: Wnt/β-catenin signalling as the key to unlock the mystery of endogenous brain repair Aging Cell 2020 19 e13101 10.1111/acel.13101 32050297 PMC7059166 · DOI
  58. [65]Pascual M. Ibáñez F. Guerri C. Exosomes as mediators of neuron-glia communication in neuroinflammation Neural Regen. Res. 2020 15 796 10.4103/1673-5374.268893 31719239 PMC6990780 · DOI
  59. [66]Basso M. Bonetto V. Extracellular Vesicles and a Novel Form of Communication in the Brain Front. Neurosci. 2016 10 127 10.3389/fnins.2016.00127 27065789 PMC4814526 · DOI
  60. [67]Colombo M. Raposo G. Théry C. Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles Annu. Rev. Cell Dev. Biol. 2014 30 255 289 10.1146/annurev-cellbio-101512-122326 25288114 · DOI · Paper page
  61. [68]Kowal J. Arras G. Colombo M. Jouve M. Morath J.P. Primdal-Bengtson B. Dingli F. Loew D. Tkach M. Théry C. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes Proc. Natl. Acad. Sci. USA 2016 113 E968 E977 10.1073/pnas.1521230113 26858453 PMC4776515 · DOI · Paper page
  62. [69]Théry C. Witwer K.W. Aikawa E. Alcaraz M.J. Anderson J.D. Andriantsitohaina R. Antoniou A. Arab T. Archer F. Atkin-Smith G.K. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines J. Extracell. Vesicles 2018 7 10.1080/20013078.2018.1535750 PMC6322352 30637094 · DOI · Paper page
  63. [70]Yu H. Sun T. An J. Wen L. Liu F. Bu Z. Cui Y. Feng J. Potential Roles of Exosomes in Parkinson’s Disease: From Pathogenesis, Diagnosis, and Treatment to Prognosis Front. Cell Dev. Biol. 2020 8 86 10.3389/fcell.2020.00086 32154247 PMC7047039 · DOI
  64. [71]Tofaris G.K. Lysosome-dependent pathways as a unifying theme in Parkinson’s disease Mov. Disord. 2012 27 1364 1369 10.1002/mds.25136 22927213 · DOI
  65. [72]Perrett R.M. Alexopoulou Z. Tofaris G.K. The endosomal pathway in Parkinson’s disease Mol. Cell. Neurosci. 2015 66 21 28 10.1016/j.mcn.2015.02.009 25701813 · DOI
  66. [73]Tancini B. Buratta S. Sagini K. Costanzi E. Delo F. Urbanelli L. Emiliani C. Insight into the Role of Extracellular Vesicles in Lysosomal Storage Disorders Genes 2019 10 510 10.3390/genes10070510 31284546 PMC6679199 · DOI
  67. [74]Charvin D. Medori R. Hauser R.A. Rascol O. Therapeutic strategies for Parkinson disease: Beyond dopaminergic drugs Nat. Rev. Drug Discov. 2018 17 804 822 10.1038/nrd.2018.136 30262889 · DOI
  68. [75]Skaper S.D. Facci L. Zusso M. Giusti P. An Inflammation-Centric View of Neurological Disease: Beyond the Neuron Front. Cell. Neurosci. 2018 12 12 10.3389/fncel.2018.00072 29618972 PMC5871676 · DOI
  69. [76]Subhramanyam C.S. Wang C. Hu Q. Dheen S.T. Microglia-mediated neuroinflammation in neurodegenerative diseases Semin. Cell Dev. Biol. 2019 94 112 120 10.1016/j.semcdb.2019.05.004 31077796 · DOI
  70. [77]Bendor J.T. Logan T.P. Edwards R.H. The function of α-synuclein Neuron 2013 79 1044 1066 10.1016/j.neuron.2013.09.004 24050397 PMC3866954 · DOI · Paper page
  71. [80]Lema Tomé C.M. Tyson T. Rey N.L. Grathwohl S. Britschgi M. Brundin P. Inflammation and α-Synuclein’s Prion-like Behavior in Parkinson’s Disease—Is There a Link? Mol. Neurobiol. 2013 47 561 574 10.1007/s12035-012-8267-8 22544647 PMC3589652 · DOI
  72. [81]Chung C.Y. Khurana V. Auluck P.K. Tardiff D.F. Mazzulli J.R. Soldner F. Baru V. Lou Y. Freyzon Y. Cho S. Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons Science 2013 342 983 987 10.1126/science.1245296 24158904 PMC4022187 · DOI
  73. [82]Braak H. De Vos R.A.I. Bohl J. Del Tredici K. Gastric α-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology Neurosci. Lett. 2006 396 67 72 10.1016/j.neulet.2005.11.012 16330147 · DOI · Paper page
  74. [84]Surgucheva I. He S. Rich M.C. Sharma R. Ninkina N.N. Stahel P.F. Surguchov A. Role of synucleins in traumatic brain injury—An experimental in vitro and in vivo study in mice Mol. Cell. Neurosci. 2014 63 114 123 10.1016/j.mcn.2014.10.005 25447944 · DOI
  75. [85]Collier T.J. Lipton J. Daley B.F. Palfi S. Chu Y. Sortwell C. Bakay R.A.E. Sladek J.R. Kordower J.H. Aging-related changes in the nigrostriatal dopamine system and the response to MPTP in nonhuman primates: Diminished compensatory mechanisms as a prelude to parkinsonism Neurobiol. Dis. 2007 26 56 65 10.1016/j.nbd.2006.11.013 17254792 PMC1899875 · DOI · Paper page
  76. [86]Kanaan N.M. Kordower J.H. Collier T.J. Age-related changes in dopamine transporters and accumulation of 3-nitrotyrosine in rhesus monkey midbrain dopamine neurons: Relevance in selective neuronal vulnerability to degeneration Eur. J. Neurosci. 2008 27 3205 3215 10.1111/j.1460-9568.2008.06307.x 18598263 PMC3391583 · DOI
  77. [87]Boger H.A. Granholm A.-C. McGinty J.F. Middaugh L.D. A dual-hit animal model for age-related parkinsonism Prog. Neurobiol. 2010 90 217 229 10.1016/j.pneurobio.2009.10.013 19853012 PMC3991553 · DOI
  78. [88]Rodriguez M. Rodriguez-Sabate C. Morales I. Sanchez A. Sabate M. Parkinson’s disease as a result of aging Aging Cell 2015 14 293 308 10.1111/acel.12312 25677794 PMC4406659 · DOI · Paper page
  79. [89]Giguère N. Burke Nanni S. Trudeau L.-E. On Cell Loss and Selective Vulnerability of Neuronal Populations in Parkinson’s Disease Front. Neurol. 2018 9 9 10.3389/fneur.2018.00455 29971039 PMC6018545 · DOI
  80. [91]Collier T.J. Kanaan N.M. Kordower J.H. Aging and Parkinson’s disease: Different sides of the same coin? Mov. Disord. 2017 32 983 990 10.1002/mds.27037 28520211 PMC5844262 · DOI
  81. [93]Hornykiewicz O. Parkinson’s disease and the adaptive capacity of the nigrostriatal dopamine system: Possible neurochemical mechanisms Adv. Neurol 1993 60 140 147 8420131
  82. [94]Bezard E. Gross C.E. Compensatory mechanisms in experimental and human parkinsonism: Towards a dynamic approach Prog. Neurobiol. 1998 10.1016/S0301-0082(98)00006-9 9618745 · DOI
  83. [95]Hindle J.V. Ageing, neurodegeneration and Parkinson’s disease Age Ageing 2010 39 156 161 10.1093/ageing/afp223 20051606 · DOI
  84. [96]De La Fuente-Fernández R. Schulzer M. Kuramoto L. Cragg J. Ramachandiran N. Au W.L. Mak E. McKenzie J. McCormick S. Sossi V. Age-specific progression of nigrostriatal dysfunction in Parkinson’s disease Ann. Neurol. 2011 69 803 810 10.1002/ana.22284 21246604 · DOI · Paper page
  85. [98]Njie E.M.G. Boelen E. Stassen F.R. Steinbusch H.W.M. Borchelt D.R. Streit W.J. Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function Neurobiol. Aging 2012 10.1016/j.neurobiolaging.2010.05.008 PMC4162517 20580465 · DOI · Paper page
  86. [99]Perry V.H. Teeling J. Microglia and macrophages of the central nervous system: The contribution of microglia priming and systemic inflammation to chronic neurodegeneration Semin. Immunopathol. 2013 35 601 612 10.1007/s00281-013-0382-8 23732506 PMC3742955 · DOI
  87. [100]Tansey M.G. Goldberg M.S. Neuroinflammation in Parkinson’s disease: Its role in neuronal death and implications for therapeutic intervention Neurobiol. Dis. 2010 37 510 518 10.1016/j.nbd.2009.11.004 19913097 PMC2823829 · DOI · Paper page
  88. [101]Tansey M.G. McCoy M.K. Frank-Cannon T.C. Neuroinflammatory mechanisms in Parkinson’s disease: Potential environmental triggers, pathways, and targets for early therapeutic intervention Exp. Neurol. 2007 208 1 25 10.1016/j.expneurol.2007.07.004 17720159 PMC3707134 · DOI
  89. [102]El Ayadi A. Zigmond M.J. Smith A.D. IGF-1 protects dopamine neurons against oxidative stress: Association with changes in phosphokinases Exp. Brain Res. 2016 234 1863 1873 10.1007/s00221-016-4572-1 26894890 PMC4893922 · DOI
  90. [103]Jha M.K. Kim J.-H. Song G.J. Lee W.-H. Lee I.-K. Lee H.-W. An S.S.A. Kim S. Suk K. Functional dissection of astrocyte-secreted proteins: Implications in brain health and diseases Prog. Neurobiol. 2018 162 37 69 10.1016/j.pneurobio.2017.12.003 29247683 · DOI
  91. [104]Serapide M.F. L’Episcopo F. Tirolo C. Testa N. Caniglia S. Giachino C. Marchetti B. Boosting Antioxidant Self-defenses by Grafting Astrocytes Rejuvenates the Aged Microenvironment and Mitigates Nigrostriatal Toxicity in Parkinsonian Brain via an Nrf2-Driven Wnt/β-Catenin Prosurvival Axis Front. Aging Neurosci. 2020 12 24 10.3389/fnagi.2020.00024 32226376 PMC7081734 · DOI
  92. [105]Barkho B.Z. Song H. Aimone J.B. Smrt R.D. Kuwabara T. Nakashima K. Gage F.H. Zhao X. Identification of Astrocyte-expressed Factors That Modulate Neural Stem/Progenitor Cell Differentiation Stem Cells Dev. 2006 15 407 421 10.1089/scd.2006.15.407 16846377 PMC2777811 · DOI
  93. [106]Jiao J. Chen D.F. Induction of Neurogenesis in Nonconventional Neurogenic Regions of the Adult Central Nervous System by Niche Astrocyte-Produced Signals Stem Cells 2008 26 1221 1230 10.1634/stemcells.2007-0513 18323412 PMC2683670 · DOI
  94. [107]Oberheim N.A. Goldman S.A. Nedergaard M. Heterogeneity of Astrocytic Form and Function Methods Mol. Biol. 2012 23 45 10.1007/978-1-61779-452-0_3 PMC3506190 22144298 · DOI · Paper page
  95. [108]Engele J. Bohn M.C. The neurotrophic effects of fibroblast growth factors on dopaminergic neurons in vitro are mediated by mesencephalic glia J. Neurosci. 1991 11 3070 3078 10.1523/JNEUROSCI.11-10-03070.1991 1941074 PMC6575454 · DOI
  96. [109]Lin L.F.H. Doherty D.H. Lile J.D. Bektesh S. Collins F. GDNF: A glial cell line—Derived neurotrophic factor for midbrain dopaminergic neurons Science 1993 260 1130 1132 10.1126/science.8493557 8493557 · DOI
  97. [110]Takeshima T. Johnston J.M. Commissiong J.W. Mesencephalic type 1 astrocytes rescue dopaminergic neurons from death induced by serum deprivation J. Neurosci. 1994 14 4769 4779 10.1523/JNEUROSCI.14-08-04769.1994 7913955 PMC6577161 · DOI
  98. [111]Sandhu J.K. Gardaneh M. Iwasiow R. Lanthier P. Gangaraju S. Ribecco-Lutkiewicz M. Tremblay R. Kiuchi K. Sikorska M. Astrocyte-secreted GDNF and glutathione antioxidant system protect neurons against 6OHDA cytotoxicity Neurobiol. Dis. 2009 33 405 414 10.1016/j.nbd.2008.11.016 19118631 · DOI
  99. [112]Yang F. Liu Y. Tu J. Wan J. Zhang J. Wu B. Chen S. Zhou J. Mu Y. Wang L. Activated astrocytes enhance the dopaminergic differentiation of stem cells and promote brain repair through bFGF Nat. Commun. 2014 5 5627 10.1038/ncomms6627 25517983 PMC4284631 · DOI
  100. [113]Burda J.E. Sofroniew M.V. Reactive Gliosis and the Multicellular Response to CNS Damage and Disease Neuron 2014 81 229 248 10.1016/j.neuron.2013.12.034 24462092 PMC3984950 · DOI
  101. [114]Tyzack G.E. Sitnikov S. Barson D. Adams-Carr K.L. Lau N.K. Kwok J.C. Zhao C. Franklin R.J.M. Karadottir R.T. Fawcett J.W. Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression Nat. Commun. 2014 5 4294 10.1038/ncomms5294 25014177 PMC4104454 · DOI
  102. [115]Faulkner J.R. Herrmann J.E. Woo M.J. Tansey K.E. Doan N.B. Sofroniew M.V. Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury J. Neurosci. 2004 24 2143 2155 10.1523/JNEUROSCI.3547-03.2004 14999065 PMC6730429 · DOI
  103. [117]Kuter K. Olech Ł. Głowacka U. Prolonged Dysfunction of Astrocytes and Activation of Microglia Accelerate Degeneration of Dopaminergic Neurons in the Rat Substantia Nigra and Block Compensation of Early Motor Dysfunction Induced by 6-OHDA Mol. Neurobiol. 2018 10.1007/s12035-017-0529-z PMC5842510 28466266 · DOI
  104. [118]Subramaniam S.R. Federoff H.J. Targeting Microglial Activation States as a Therapeutic Avenue in Parkinson’s Disease Front. Aging Neurosci. 2017 9 176 10.3389/fnagi.2017.00176 28642697 PMC5463358 · DOI
  105. [119]Yulei X. Qiwei Z. IL-1β enhances the antibacterial activity of astrocytes by activation of NF-κB Glia 2010 10.1002/glia.20921 19672968 · DOI
  106. [120]Choi I. Kim J. Jeong H.K. Kim B. Jou I. Park M. Chen L. Kang U.J. Zhuang X. Joe E. hye PINK1 deficiency attenuates astrocyte proliferation through mitochondrial dysfunction, reduced AKT and increased p38 MAPK activation, and downregulation of EGFR Glia 2013 61 800 812 10.1002/glia.22475 23440919 PMC3657120 · DOI
  107. [121]Sahin-Calapoglu N. Demirci S. Calapoglu M. Yasar B. A Case-Control Association Study of RANTES (-28 C > G) Polymorphism as a Risk Factor for Parkinson’s Disease in Isparta, Turkey Parkinsons Dis. 2016 2016 1 7 10.1155/2016/5042604 28078161 PMC5203900 · DOI
  108. [124]L’Episcopo F. Tirolo C. Testa N. Caniglia S. Morale M.C. Impagnatiello F. Pluchino S. Marchetti B. Aging-Induced Nrf2-ARE Pathway Disruption in the Subventricular Zone Drives Neurogenic Impairment in Parkinsonian Mice via PI3K-Wnt/ -Catenin Dysregulation J. Neurosci. 2013 33 1462 1485 10.1523/JNEUROSCI.3206-12.2013 23345222 PMC3564519 · DOI
  109. [125]L’Episcopo F. Tirolo C. Peruzzotti-Jametti L. Serapide M.F. Testa N. Caniglia S. Balzarotti B. Pluchino S. Marchetti B. Neural Stem Cell Grafts Promote Astroglia-driven Neurorestoration in the Aged Parkinsonian Brain via Wnt/β-catenin Signalling Stem Cells 2018 36 1179 1197 10.1002/stem.2827 29575325 · DOI
  110. [126]Wurst W. Prakash N. Wnt1-regulated genetic networks in midbrain dopaminergic neuron development J. Mol. Cell Biol. 2014 6 34 41 10.1093/jmcb/mjt046 24326514 · DOI
  111. [127]Arenas E. Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson’s disease J. Mol. Cell Biol. 2014 6 42 53 10.1093/jmcb/mju001 24431302 · DOI
  112. [128]Brodski C. Blaess S. Partanen J. Prakash N. Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells J. Dev. Biol. 2019 7 3 10.3390/jdb7010003 PMC6473842 30650592 · DOI
  113. [129]Marchetti B. Wnt/β-catenin signaling pathway governs a full program for dopaminergic neuron survival, neurorescue and regeneration in the MPTP mouse model of Parkinson’s disease Int. J. Mol. Sci. 2018 19 3743 10.3390/ijms19123743 PMC6321180 30477246 · DOI
  114. [130]Alvarez-Buylla A. García-Verdugo J.M. Tramontin A.D. A unified hypothesis on the lineage of neural stem cells Nat. Rev. Neurosci. 2001 10.1038/35067582 11283751 · DOI
  115. [131]Lie D.C. Colamarino S.A. Song H.J. Désiré L. Mira H. Consiglio A. Lein E.S. Jessberger S. Lansford H. Dearie A.R. Wnt signalling regulates adult hippocampal neurogenesis Nature 2005 437 1370 1375 10.1038/nature04108 16251967 · DOI
  116. [132]Cahoy J.D. Emery B. Kaushal A. Foo L.C. Zamanian J.L. Christopherson K.S. Xing Y. Lubischer J.L. Krieg P.A. Krupenko S.A. A transcriptome database for astrocytes, neurons, and oligodendrocytes: A new resource for understanding brain development and function J. Neurosci. 2008 28 264 278 10.1523/JNEUROSCI.4178-07.2008 18171944 PMC6671143 · DOI · Paper page
  117. [133]Toledo E.M. Gyllborg D. Arenas E. Translation of WNT developmental programs into stem cell replacement strategies for the treatment of Parkinson’s disease Br. J. Pharmacol. 2017 174 4716 4724 10.1111/bph.13871 28547771 PMC5727333 · DOI
  118. [134]Batchelor P.E. Liberatore G.T. Wong J.Y.F. Porritt M.J. Frerichs F. Donnan G.A. Howells D.W. Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor J. Neurosci. 1999 19 1708 1716 10.1523/JNEUROSCI.19-05-01708.1999 10024357 PMC6782182 · DOI
  119. [135]Zigmond M.J. Cameron J.L. Leak R.K. Mirnics K. Russell V.A. Smeyne R.J. Smith A.D. Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency Park. Relat. Disord. 2009 15 S42 S45 10.1016/S1353-8020(09)70778-3 20083005 · DOI · Paper page
  120. [136]Arkadir D. Bergman H. Fahn S. Redundant dopaminergic activity may enable compensatory axonal sprouting in Parkinson disease Neurology 2014 82 1093 1098 10.1212/WNL.0000000000000243 24663231 · DOI
  121. [137]Blesa J. Trigo-Damas I. Dileone M. del Rey N.L.-G. Hernandez L.F. Obeso J.A. Compensatory mechanisms in Parkinson’s disease: Circuits adaptations and role in disease modification Exp. Neurol. 2017 298 148 161 10.1016/j.expneurol.2017.10.002 28987461 · DOI
  122. [138]Ho A. Blum M. Induction of interleukin-1 associated with compensatory dopaminergic sprouting in the denervated striatum of young mice: Model of aging and neurodegenerative disease J. Neurosci. 1998 18 5614 5629 10.1523/JNEUROSCI.18-15-05614.1998 9671653 PMC6793059 · DOI
  123. [139]Parish C.L. Finkelstein D.I. Tripanichkul W. Satoskar A.R. Drago J. Horne M.K. The role of interleukin-1, interleukin-6, and glia in inducing growth of neuronal terminal arbors in mice J. Neurosci. 2002 22 8034 8041 10.1523/JNEUROSCI.22-18-08034.2002 12223557 PMC6758077 · DOI
  124. [140]Stanic D. Finkelstein D.I. Bourke D.W. Drago J. Horne M.K. Timecourse of striatal re-innervation following lesions of dopaminergic SNpc neurons of the rat Eur. J. Neurosci. 2003 18 1175 1188 10.1046/j.1460-9568.2003.02800.x 12956716 · DOI
  125. [141]L’Episcopo F. Tirolo C. Testa N. Caniglia S. Morale M.C. Serapide M.F. Pluchino S. Marchetti B. Wnt/β-Catenin Signaling Is Required to Rescue Midbrain Dopaminergic Progenitors and Promote Neurorepair in Ageing Mouse Model of Parkinson’s Disease Stem Cells 2014 32 2147 2163 10.1002/stem.1708 24648001 PMC4106883 · DOI
  126. [142]L’Episcopo F. Tirolo C. Caniglia S. Testa N. Morale M.C. Serapide M.F. Pluchino S. Marchetti B. Targeting Wnt signaling at the neuroimmune interface for dopaminergic neuroprotection/repair in Parkinson’s disease J. Mol. Cell Biol. 2014 6 13 26 10.1093/jmcb/mjt053 24431301 PMC4061726 · DOI
  127. [143]Marchetti B. Pluchino S. Wnt your brain be inflamed? Yes, it Wnt! Trends Mol. Med. 2013 19 144 156 10.1016/j.molmed.2012.12.001 23312954 PMC3595301 · DOI
  128. [144]L’Episcopo F. Tirolo C. Testa N. Caniglia S. Morale M.C. Deleidi M. Serapide M.F. Pluchino S. Marchetti B. Plasticity of subventricular zone neuroprogenitors in MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine) mouse model of Parkinson’s disease involves cross talk between inflammatory and Wnt/β-catenin signaling pathways: Functional consequences for neuropr J. Neurosci. 2012 32 2062 2085 10.1523/JNEUROSCI.5259-11.2012 22323720 PMC3556384 · DOI
  129. [145]Vella L. Hill A. Cheng L. Focus on Extracellular Vesicles: Exosomes and Their Role in Protein Trafficking and Biomarker Potential in Alzheimer’s and Parkinson’s Disease Int. J. Mol. Sci. 2016 17 173 10.3390/ijms17020173 26861304 PMC4783907 · DOI
  130. [146]Iraci N. Leonardi T. Gessler F. Vega B. Pluchino S. Focus on Extracellular Vesicles: Physiological Role and Signalling Properties of Extracellular Membrane Vesicles Int. J. Mol. Sci 2016 17 171 10.3390/ijms17020171 26861302 PMC4783905 · DOI · Paper page
  131. [147]Jellinger K.A. Interaction between -Synuclein and Other Proteins in Neurodegenerative Disorders Sci. World J. 2011 11 1893 1907 10.1100/2011/371893 PMC3217595 22125446 · DOI
  132. [148]Meade R.M. Fairlie D.P. Mason J.M. Alpha-synuclein structure and Parkinson’s disease—Lessons and emerging principles Mol. Neurodegener. 2019 14 29 10.1186/s13024-019-0329-1 31331359 PMC6647174 · DOI
  133. [149]Gustafsson G. Lööv C. Persson E. Lázaro D.F. Takeda S. Bergström J. Erlandsson A. Sehlin D. Balaj L. György B. Secretion and Uptake of α-Synuclein Via Extracellular Vesicles in Cultured Cells Cell. Mol. Neurobiol. 2018 38 1539 1550 10.1007/s10571-018-0622-5 30288631 PMC6223723 · DOI
  134. [150]Lee H.J. Patel S. Lee S.J. Intravesicular localization and exocytosis of α-synuclein and its aggregates J. Neurosci. 2005 25 6016 6024 10.1523/JNEUROSCI.0692-05.2005 15976091 PMC6724798 · DOI
  135. [151]Burré J. Sharma M. Südhof T.C. Cell biology and pathophysiology of α-synuclein Cold Spring Harb. Perspect. Med. 2018 8 a024091 10.1101/cshperspect.a024091 28108534 PMC5519445 · DOI
  136. [153]Harischandra D.S. Ghaisas S. Rokad D. Zamanian M. Jin H. Anantharam V. Kimber M. Kanthasamy A. Kanthasamy A.G. Environmental neurotoxicant manganese regulates exosome-mediated extracellular miRNAs in cell culture model of Parkinson’s disease: Relevance to α-synuclein misfolding in metal neurotoxicity Neurotoxicology 2017 64 267 277 10.1016/j.neuro.2017.04.007 28450057 PMC5654692 · DOI
  137. [154]Lee H.-J. Suk J.-E. Patrick C. Bae E.-J. Cho J.-H. Rho S. Hwang D. Masliah E. Lee S.-J. Direct Transfer of α-Synuclein from Neuron to Astroglia Causes Inflammatory Responses in Synucleinopathies J. Biol. Chem. 2010 285 9262 9272 10.1074/jbc.M109.081125 20071342 PMC2838344 · DOI · Paper page
  138. [155]Alvarez-Erviti L. Couch Y. Richardson J. Cooper J.M. Wood M.J.A. Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line Neurosci. Res. 2011 69 337 342 10.1016/j.neures.2010.12.020 21255620 · DOI
  139. [156]Chang C. Lang H. Geng N. Wang J. Li N. Wang X. Exosomes of BV-2 cells induced by alpha-synuclein: Important mediator of neurodegeneration in PD Neurosci. Lett. 2013 548 190 195 10.1016/j.neulet.2013.06.009 23792198 · DOI
  140. [157]Bliederhaeuser C. Grozdanov V. Speidel A. Zondler L. Ruf W.P. Bayer H. Kiechle M. Feiler M.S. Freischmidt A. Brenner D. Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes Acta Neuropathol. 2016 131 379 391 10.1007/s00401-015-1504-2 26576561 · DOI
  141. [158]Tsutsumi R. Hori Y. Seki T. Kurauchi Y. Sato M. Oshima M. Hisatsune A. Katsuki H. Involvement of exosomes in dopaminergic neurodegeneration by microglial activation in midbrain slice cultures Biochem. Biophys. Res. Commun. 2019 511 427 433 10.1016/j.bbrc.2019.02.076 30803759 · DOI
  142. [159]Xia Y. Zhang G. Han C. Ma K. Guo X. Wan F. Kou L. Yin S. Liu L. Huang J. Microglia as modulators of exosomal alpha-synuclein transmission Cell Death Dis. 2019 10 174 10.1038/s41419-019-1404-9 30787269 PMC6382842 · DOI
  143. [160]Leggio L. Vivarelli S. L’Episcopo F. Tirolo C. Caniglia S. Testa N. Marchetti B. Iraci N. microRNAs in Parkinson’s Disease: From Pathogenesis to Novel Diagnostic and Therapeutic Approaches Int. J. Mol. Sci. 2017 18 2698 10.3390/ijms18122698 PMC5751299 29236052 · DOI
  144. [161]Winkler C.W. Taylor K.G. Peterson K.E. Location Is Everything: Let-7b microRNA and TLR7 Signaling Results in a Painful TRP Sci. Signal. 2014 7 pe14 10.1126/scisignal.2005407 24866018 · DOI
  145. [162]Asikainen S. Rudgalvyte M. Heikkinen L. Louhiranta K. Lakso M. Wong G. Nass R. Global microRNA Expression Profiling of Caenorhabditis elegans Parkinson’s Disease Models J. Mol. Neurosci. 2010 41 210 218 10.1007/s12031-009-9325-1 20091141 · DOI · Paper page
  146. [164]Venturini A. Passalacqua M. Pelassa S. Pastorino F. Tedesco M. Cortese K. Gagliani M.C. Leo G. Maura G. Guidolin D. Exosomes from astrocyte processes: Signaling to neurons Front. Pharmacol. 2019 10 1452 10.3389/fphar.2019.01452 31849688 PMC6901013 · DOI
  147. [165]Willis C.M. Ménoret A. Jellison E.R. Nicaise A.M. Vella A.T. Crocker S.J. A Refined Bead-Free Method to Identify Astrocytic Exosomes in Primary Glial Cultures and Blood Plasma Front. Neurosci. 2017 11 10.3389/fnins.2017.00335 28663721 PMC5471332 · DOI
  148. [167]Li N. Wu Y. Zhu L. Huang Y. Liu Z. Shi M. Soltys D. Zhang J. Chang Q. Extracellular microvesicles-derived from microglia treated with unaggregated α-synuclein attenuate mitochondrial fission and toxicity-induced by Parkinsonian toxin MPP+ Biochem. Biophys. Res. Commun. 2019 517 642 647 10.1016/j.bbrc.2019.07.084 31402119 · DOI
  149. [168]Afridi R. Kim J.-H. Rahman M.H. Suk K. Metabolic Regulation of Glial Phenotypes: Implications in Neuron–Glia Interactions and Neurological Disorders Front. Cell. Neurosci. 2020 14 20 10.3389/fncel.2020.00020 32116564 PMC7026370 · DOI
  150. [170]Tamboli I.Y. Barth E. Christian L. Siepmann M. Kumar S. Singh S. Tolksdorf K. Heneka M.T. Lütjohann D. Wunderlich P. Statins promote the degradation of extracellular amyloid β-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion J. Biol. Chem. 2010 285 37405 37414 10.1074/jbc.M110.149468 20876579 PMC2988346 · DOI
  151. [171]Udeochu J.C. Sanchez-Diaz C. Cai A. Jovicic A. Villeda S.A. Exosome Release Promotes Inflammatory Resolution in Activated and Aged Microglia bioRxiv 2018 10.1101/423558 · DOI
  152. [172]Krämer-Albers E.M. Bretz N. Tenzer S. Winterstein C. Möbius W. Berger H. Nave K.A. Schild H. Trotter J. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons? Proteom. Clin. Appl. 2007 1 1446 1461 10.1002/prca.200700522 21136642 · DOI
  153. [173]Frühbeis C. Fröhlich D. Kuo W.P. Amphornrat J. Thilemann S. Saab A.S. Kirchhoff F. Möbius W. Goebbels S. Nave K.A. Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte-Neuron Communication PLoS Biol. 2013 11 e1001604 10.1371/journal.pbio.1001604 23874151 PMC3706306 · DOI · Paper page
  154. [174]Fröhlich D. Kuo W.P. Frühbeis C. Sun J.J. Zehendner C.M. Luhmann H.J. Pinto S. Toedling J. Trotter J. Krämer-Albers E.M. Multifaceted effects of oligodendroglial exosomes on neurons: Impact on neuronal firing rate, signal transduction and gene regulation Philos. Trans. R. Soc. B Biol. Sci. 2014 369 20130510 10.1098/rstb.2013.0510 PMC4142031 25135971 · DOI · Paper page
  155. [175]Taylor A.R. Robinson M.B. Gifondorwa D.J. Tytell M. Milligan C.E. Regulation of heat shock protein 70 release in astrocytes: Role of signaling kinases Dev. Neurobiol. 2007 67 1815 1829 10.1002/dneu.20559 17701989 · DOI
  156. [176]Wang S. Cesca F. Loers G. Schweizer M. Buck F. Benfenati F. Schachner M. Kleene R. Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes J. Neurosci. 2011 31 7275 7290 10.1523/JNEUROSCI.6476-10.2011 21593312 PMC6622588 · DOI · Paper page
  157. [177]Pascua-Maestro R. González E. Lillo C. Ganfornina M.D. Falcón-Pérez J.M. Sanchez D. Extracellular vesicles secreted by astroglial cells transport apolipoprotein D to neurons and mediate neuronal survival upon oxidative stress Front. Cell. Neurosci. 2019 12 10.3389/fncel.2018.00526 PMC6335244 30687015 · DOI
  158. [178]Shakespear N. Ogura M. Yamaki J. Homma Y. Astrocyte-Derived Exosomal microRNA miR-200a-3p Prevents MPP+-Induced Apoptotic Cell Death Through Down-Regulation of MKK4 Neurochem. Res. 2020 45 1020 1033 10.1007/s11064-020-02977-5 32016794 · DOI
  159. [179]Leggio L. L’Episcopo F. Vivarelli S. Tirolo C. Testa N. Caniglia S. Bastos C. Faria N. Navas M.J.U. Verdugo J.M.G. Ultrastructural and molecular characterization of astrocyte-derived extracellular vesicles from nigrostriatal brain regions: Implications for dopaminergic neuroprotection T09-090C Proceedings of the GLIA 2019 XIV European Meeting on Glial Cells in Health and Disease, Porto, Portugal, 10–13 July 2019 Wiley Hoboken, NJ, USA 2019 Volume 67 E380 E381
  160. [180]Wu X. Zheng T. Zhang B. Exosomes in Parkinson’s Disease Neurosci. Bull. 2017 33 331 338 10.1007/s12264-016-0092-z 28025780 PMC5567508 · DOI
  161. [181]Doyle L.M. Wang M.Z. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis Cells 2019 8 727 10.3390/cells8070727 PMC6678302 31311206 · DOI
  162. [182]Slota J.A. Booth S.A. MicroRNAs in Neuroinflammation: Implications in Disease Pathogenesis, Biomarker Discovery and Therapeutic Applications Non-Coding RNA 2019 5 35 10.3390/ncrna5020035 31022830 PMC6632112 · DOI
  163. [183]Cho K.J. Song J. Oh Y. Lee J.E. MicroRNA-Let-7a regulates the function of microglia in inflammation Mol. Cell. Neurosci. 2015 68 167 176 10.1016/j.mcn.2015.07.004 26221772 · DOI
  164. [184]Zhang G. Xia Y. Wan F. Ma K. Guo X. Kou L. Yin S. Han C. Liu L. Huang J. New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease Front. Aging Neurosci. 2018 10 10.3389/fnagi.2018.00370 PMC6261981 30524265 · DOI
  165. [185]Niu M. Li Y. Li G. Zhou L. Luo N. Yao M. Kang W. Liu J. A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson’s disease development and progression Eur. J. Neurol. 2020 27 967 974 10.1111/ene.14208 32150777 · DOI · Paper page
  166. [186]Chiasserini D. Van Weering J.R.T. Piersma S.R. Pham T.V. Malekzadeh A. Teunissen C.E. De Wit H. Jiménez C.R. Proteomic analysis of cerebrospinal fluid extracellular vesicles: A comprehensive dataset J. Proteom. 2014 106 191 204 10.1016/j.jprot.2014.04.028 24769233 · DOI
  167. [187]Tomlinson P.R. Zheng Y. Fischer R. Heidasch R. Gardiner C. Evetts S. Hu M. Wade-Martins R. Turner M.R. Morris J. Identification of distinct circulating exosomes in Parkinson’s disease Ann. Clin. Transl. Neurol. 2015 2 353 361 10.1002/acn3.175 25909081 PMC4402081 · DOI
  168. [188]Jiang Y. Liu J. Chen L. Jin Y. Zhang G. Lin Z. Du S. Fu Z. Chen T. Qin Y. Serum secreted miR-137-containing exosomes affects oxidative stress of neurons by regulating OXR1 in Parkinson’s disease Brain Res. 2019 1722 146331 10.1016/j.brainres.2019.146331 31301273 · DOI
  169. [189]Ohmichi T. Mitsuhashi M. Tatebe H. Kasai T. Ali El-Agnaf O.M. Tokuda T. Quantification of brain-derived extracellular vesicles in plasma as a biomarker to diagnose Parkinson’s and related diseases Park. Relat. Disord. 2019 61 82 87 10.1016/j.parkreldis.2018.11.021 30502924 · DOI
  170. [190]Cao X.Y. Lu J.M. Zhao Z.Q. Li M.C. Lu T. An X.S. Xue L.J. MicroRNA biomarkers of Parkinson’s disease in serum exosome-like microvesicles Neurosci. Lett. 2017 644 94 99 10.1016/j.neulet.2017.02.045 28223160 · DOI
  171. [191]Gui Y. Liu H. Zhang L. Lv W. Hu X. Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease Oncotarget 2015 6 37043 37053 10.18632/oncotarget.6158 26497684 PMC4741914 · DOI · Paper page
  172. [192]Yao Y.F. Qu M.W. Li G.C. Zhang F.B. Rui H.C. Circulating exosomal miRNAs as diagnostic biomarkers in Parkinson’s disease Eur. Rev. Med. Pharmacol. Sci. 2018 10.26355/eurrev_201808_15727 30178852 · DOI
  173. [193]Aryani A. Denecke B. Exosomes as a Nanodelivery System: A Key to the Future of Neuromedicine? Mol. Neurobiol. 2016 53 818 834 10.1007/s12035-014-9054-5 25502465 PMC4752585 · DOI
  174. [194]Porro C. Panaro M.A. Lofrumento D.D. Hasalla E. Trotta T. The multiple roles of exosomes in Parkinson’s disease: An overview Immunopharmacol. Immunotoxicol. 2019 41 469 476 10.1080/08923973.2019.1650371 31405314 · DOI
  175. [196]Cooper J.M. Wiklander P.B.O. Nordin J.Z. Al-Shawi R. Wood M.J. Vithlani M. Schapira A.H.V. Simons J.P. El-Andaloussi S. Alvarez-Erviti L. Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice Mov. Disord. 2014 29 1476 1485 10.1002/mds.25978 25112864 PMC4204174 · DOI
  176. [197]Izco M. Blesa J. Schleef M. Schmeer M. Porcari R. Al-Shawi R. Ellmerich S. de Toro M. Gardiner C. Seow Y. Systemic Exosomal Delivery of shRNA Minicircles Prevents Parkinsonian Pathology Mol. Ther. 2019 27 2111 2122 10.1016/j.ymthe.2019.08.010 31501034 PMC6904801 · DOI
  177. [198]Vilaça-Faria H. Salgado A.J. Teixeira F.G. Mesenchymal Stem Cells-derived Exosomes: A New Possible Therapeutic Strategy for Parkinson’s Disease? Cells 2019 8 118 10.3390/cells8020118 PMC6406999 30717429 · DOI
  178. [199]Haney M.J. Zhao Y. Harrison E.B. Mahajan V. Ahmed S. He Z. Suresh P. Hingtgen S.D. Klyachko N.L. Mosley R.L. Specific Transfection of Inflamed Brain by Macrophages: A New Therapeutic Strategy for Neurodegenerative Diseases PLoS ONE 2013 8 e61852 10.1371/journal.pone.0061852 23620794 PMC3631190 · DOI
  179. [200]Zhao Y. Haney M.J. Gupta R. Bohnsack J.P. He Z. Kabanov A.V. Batrakova E.V. GDNF-transfected macrophages produce potent neuroprotective effects in Parkinson’s disease mouse model PLoS ONE 2014 9 e106867 10.1371/journal.pone.0106867 25229627 PMC4167552 · DOI
  180. [201]Jarmalavičiute A. Tunaitis V. Pivoraite U. Venalis A. Pivoriunas A. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis Cytotherapy 2015 17 932 939 10.1016/j.jcyt.2014.07.013 25981557 · DOI
  181. [202]Narbute K. Piļipenko V. Pupure J. Dzirkale Z. Jonavičė U. Tunaitis V. Kriaučiūnaitė K. Jarmalavičiūtė A. Jansone B. Kluša V. Intranasal Administration of Extracellular Vesicles Derived from Human Teeth Stem Cells Improves Motor Symptoms and Normalizes Tyrosine Hydroxylase Expression in the Substantia Nigra and Striatum of the 6-Hydroxydopamine-Treated Rats Stem Cells Transl. Med. 2019 8 490 499 10.1002/sctm.18-0162 30706999 PMC6477008 · DOI · Paper page
  182. [203]Kojima R. Bojar D. Rizzi G. El Hamri G.C. El-Baba M.D. Saxena P. Ausländer S. Tan K.R. Fussenegger M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment Nat. Commun. 2018 9 1305 10.1038/s41467-018-03733-8 29610454 PMC5880805 · DOI · Paper page

Authors
Marchetti, B., Leggio, L., L’Episcopo, F., Vivarelli, S., Tirolo, C., Paternò, G., Giachino, C., Caniglia, S., Serapide, M. F., & Iraci, N.
Affiliations
  • University of Catania (IT)
  • Oasi Maria SS (IT)
Corresponding author
  • Marchetti, Bianca
  • Iraci, Nunzio
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2020-06-21
Volume
9
Issue
6
Pages
1941
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm9061941
PMC
PMC7356371
OpenAlex
W3037735009
Cited by
38
References
205
Citations by year
2026: 9 · 2025: 6 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 8 · 2020: 3
FWCI
0.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fondazione CON IL SUD (“Brains2South” grant)
  • Ministero della Salute (Cur. Res. and Finalized Res projects 2010-2020)
  • Università di Catania ("Bando-Chance”, PRIN-2015)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Parkinson's disease, dopaminergic neuron death, substantia nigra pars compacta, blood-brain barrier penetration, extracellular vesicle biomarkers, nanotherapeutics, neuroprotection

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