The multiple roles of exosomes in Parkinson's disease: an overview

References

• Gaceb A, Martinez MC, Andriantsitohaina R. Extracellular vesicles: new players in cardiovascular diseases. Int J Biochem Cell Biol. 2014;50:24–28.
   PubMed Web of Science ®Google Scholar
• Porro C, Trotta T, Panaro MA. Microvesicles in the brain: biomarker, messenger or mediator? J Neuroimmunol. 2015;288:70–78.
   PubMed Web of Science ®Google Scholar
• El Andaloussi S, Mäger I, Breakefield XO, et al. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12:347–357.
   PubMed Web of Science ®Google Scholar
• Tual-Chalot S, Leonetti D, Andriantsitohaina R, et al. Microvesicles: inter-cellular vectors of biological messages. Mol Interv. 2011;11:88–94.
   PubMedGoogle Scholar
• Cocucci E, Meldolesi J. Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol. 2015;25:364–372.
   PubMed Web of Science ®Google Scholar
• Caby MP, Lankar D, Vincendeau-Scherrer C, et al. Exosomal like vesicles are present in human blood plasma. Int Immunol. 2005;17:879–887.
   PubMed Web of Science ®Google Scholar
• Lässer C, Alikhani VS, Ekström K, et al. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J Transl Med. 2011;9:9.
   PubMed Web of Science ®Google Scholar
• Lässer C, O'Neil SE, Ekerljung L, et al. RNA-containing exosomes in human nasal secretions. Am J Rhinol Allergy. 2011;25:89–93.
   PubMed Web of Science ®Google Scholar
• Porro C, Lepore S, Trotta T, et al. Isolation and characterization of microparticles in sputum from cystic fibrosis patients. Respir Res. 2010;11:94.
   PubMed Web of Science ®Google Scholar
• Street JM, Barran PE, Mackay CL, et al. Identification and proteomic profiling of exosomes in human cerebrospinal fluid. J Transl Med. 2012;10:5.
   PubMed Web of Science ®Google Scholar
• Keller S, Ridinger J, Rupp AK, et al. Body fluid derived exosomes as a novel template for clinical diagnostics. J Transl Med. 2011;9:86.
   PubMed Web of Science ®Google Scholar
• Raj DA, Fiume I, Capasso G, et al. A multiplex quantitative proteomics strategy for protein biomarker studies in urinary exosomes. Kidney Int. 2012;81:1263–1272.
   PubMed Web of Science ®Google Scholar
• Porro C, Di Gioia S, Trotta T, et al. Pro-inflammatory effect of cystic fibrosis sputum microparticles in the murine lung. J Cyst Fibros. 2013;12:721–728.
   PubMed Web of Science ®Google Scholar
• Russo I, Bubacco L, Greggio E. Exosomes-associated neurodegeneration and progression of Parkinson’s disease. Am J Neurodegener Dis. 2012;1:217–225.
   PubMedGoogle Scholar
• Chinta SJ, Andersen JK. Dopaminergic neurons. Int J Biochem Cell Biol. 2005;37:942–946.
   PubMed Web of Science ®Google Scholar
• Spillantini MG, Schmidt ML, Lee VM, et al. Alpha-synuclein in Lewy bodies. Nature. 1997;388:839–840.
   PubMed Web of Science ®Google Scholar
• Brundin P, Li JY, Holton JL, et al. Research in motion: the enigma of Parkinson's disease pathology spread. Nat Rev Neurosci. 2008;9:741–745.
   PubMed Web of Science ®Google Scholar
• Braak H, Rüb U, Gai WP, et al. Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna). 2003;110:517–536.
   PubMed Web of Science ®Google Scholar
• Tsilioni I, Panagiotidou S, Theoharides TC. Exosomes in neurologic and psychiatric disorders. Clin Ther. 2014;36:882–888.
   PubMed Web of Science ®Google Scholar
• Lee HJ, Patel S, Lee SJ. Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci. 2005;25:6016–6024.
   PubMed Web of Science ®Google Scholar
• Majbour NK, Vaikath NN, Eusebi P, et al. Longitudinal changes in CSF alpha-synuclein species reflect Parkinson's disease progression. Mov Disord. 2016;31:1535–1542.
   PubMed Web of Science ®Google Scholar
• Burré J, Sharma M, Tsetsenis T, et al. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science. 2010;329:1663–1667.
   PubMed Web of Science ®Google Scholar
• Chandra S, Gallardo G, Fernández-Chacón R, et al. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell. 2005;123:383–396.
   PubMed Web of Science ®Google Scholar
• Kim C, Lee SJ. Controlling the mass action of alpha-synuclein in Parkinson's disease. J Neurochem. 2008;107:303–316.
   PubMed Web of Science ®Google Scholar
• Su X, Federoff HJ, Maguire-Zeiss KA. Mutant alpha-synuclein overexpression mediates early proinflammatory activity. Neurotox Res. 2009;16:238–254.
   PubMed Web of Science ®Google Scholar
• Trojanowski JQ, Lee VM. Parkinson's disease and related synucleinopathies are a new class of nervous system amyloidoses. Neurotoxicology. 2002;23:457–460.
   PubMed Web of Science ®Google Scholar
• Panaro MA, Cianciulli A. Current opinions and perspectives on the role of immune system in the pathogenesis of Parkinson's disease. Curr Pharm Des. 2012;18:200–208.
   PubMed Web of Science ®Google Scholar
• Eugenin EA, Eckardt D, Theis M, et al. Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon-gamma and tumor necrosis factor-alpha. Proc Natl Acad Sci USA. 2001;98:4190–4195.
   PubMed Web of Science ®Google Scholar
• Vicario M, Cieri D, Brini M, et al. The close encounter between alpha-synuclein and mitochondria. Front Neurosci. 2018;12:388.
   PubMed Web of Science ®Google Scholar
• Roodveldt C, Labrador-Garrido A, Gonzalez-Rey E, et al. Glial innate immunity generated by non-aggregated alpha-synuclein in mouse: differences between wild-type and Parkinson's disease-linked mutants. PloS One. 2010;5:e13481.
   PubMed Web of Science ®Google Scholar
• Theodore S, Cao S, McLean PJ, et al. Targeted overexpression of human alpha-synuclein triggers microglial activation and an adaptive immune response in a mouse model of Parkinson disease. J Neuropathol Exp Neurol. 2008;67:1149–1158.
   PubMed Web of Science ®Google Scholar
• Benner EJ, Banerjee R, Reynolds AD, et al. Nitrated α-synuclein immunity accelerates degeneration of nigral dopaminergic neurons. PloS One. 2008;3:e1376.
   PubMed Web of Science ®Google Scholar
• Cianciulli A, Dragone T, Calvello R, et al. IL-10 plays a pivotal role in anti-inflammatory effects of resveratrol in activated microglia cells. Int Immunopharmacol. 2015;24:369–376.
   PubMed Web of Science ®Google Scholar
• Fischer HG, Reichmann G. Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J Immunol. 2001;166:2717–2726.
   PubMed Web of Science ®Google Scholar
• Neumann H, Kotter MR, Franklin RJ. Debris clearance by microglia: an essential link between degeneration and regeneration. Brain. 2008;132:288–295.
   PubMed Web of Science ®Google Scholar
• Cianciulli A, Salvatore R, Porro C, et al. Folic acid is able to polarize the inflammatory response in LPS activated microglia by regulating multiple signaling pathways. Mediators Inflamm. 2016;2016:1.
   Google Scholar
• Joers V, Tansey MG, Mulas G, et al. Microglial phenotypes in Parkinson’s disease and animal models of the disease. Progr Neurobiol. 2017;155:57–75.
   PubMed Web of Science ®Google Scholar
• Su X, Federoff HJ. Immune responses in Parkinson's disease: interplay between central and peripheral immune systems. Biomed Res Int. 2014;2014:1.
   Google Scholar
• Orr CF, Rowe DB, Halliday GM. An inflammatory review of Parkinson's disease. Prog Neurobiol. 2002;68:325–340.
   PubMed Web of Science ®Google Scholar
• Zhang W, Wang T, Pei Z, et al. Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J. 2005;19:533–542.
   PubMed Web of Science ®Google Scholar
• Fellner L, Stefanova N. The role of glia in α-synucleinopathies. Mol Neurobiol. 2013;47:575–586.
   PubMed Web of Science ®Google Scholar
• Fellner L, Irschick R, Schanda K, et al. Toll-like receptor 4 is required for alpha-synuclein dependent activation of microglia and astroglia. Glia. 2013;61:349–360.
   PubMed Web of Science ®Google Scholar
• Kim C, Ho DH, Suk JE, et al. Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun. 2013;4:1562.
   PubMed Web of Science ®Google Scholar
• Trotta T, Porro C, Calvello R, et al. Biological role of Toll-like receptor-4 in the brain. J Neuroimmunol. 2014;268:1–12.
   PubMed Web of Science ®Google Scholar
• Fauré J, Lachenal G, Court M, et al. Exosomes are released by cultured cortical neurones. Mol Cell Neurosci. 2006;31:642–648.
   PubMed Web of Science ®Google Scholar
• Potolicchio I, Carven GJ, Xu X, et al. Proteomic analysis of microglia-derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J Immunol. 2005;175:2237–2243.
   PubMed Web of Science ®Google Scholar
• Taylor AR, Robinson MB, Gifondorwa DJ, et al. Regulation of heat shock protein 70 release in astrocytes: role of signaling kinases. Dev Neurobiol. 2007;67:1815–1829.
   PubMed Web of Science ®Google Scholar
• Bobrie A, Colombo M, Raposo G, et al. Exosome secretion: molecular mechanisms and roles in immune responses. Traffic. 2011;12:1659–1668.
   PubMed Web of Science ®Google Scholar
• Simons M, Raposo G. Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21:575–581.
   PubMed Web of Science ®Google Scholar
• Court FA, Midha R, Cisterna BA, et al. Morphological evidence for a transport of ribosomes from Schwann cells to regenerating axons. Glia. 2011;59:1529–1539.
   PubMed Web of Science ®Google Scholar
• Lachenal G, Pernet-Gallay K, Chivet M, et al. Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Mol Cell Neurosci. 2011;46:409–418.
   PubMed Web of Science ®Google Scholar
• Keller S, Sanderson MP, Stoeck A, et al. Exosomes: from biogenesis and secretion to biological function. Immunol Lett. 2006;107:102–108.
   PubMed Web of Science ®Google Scholar
• Fitzner D, Schnaars M, van Rossum D, et al. Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci. 2011;124:447–458.
   PubMed Web of Science ®Google Scholar
• Rana S, Yue S, Stadel D, et al. Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. Int J Biochem Cell Biol. 2012;44:1574–1584.
   PubMed Web of Science ®Google Scholar
• Alvarez-Erviti L, Seow Y, Yin H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29:341–345.
   PubMed Web of Science ®Google Scholar
• Haney MJ, Zhao Y, Li S, et al. Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells. Nanomedicine (London). 2011;6:1215–1230.
   PubMed Web of Science ®Google Scholar
• Haney MJ, Zhao Y, Harrison EB, et al. Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases. PLoS One. 2013;8:e61852.
   PubMed Web of Science ®Google Scholar
• Haney MJ, Klyachko NL, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson's disease therapy. J Control Release.. 2015;207:18–30.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Haney MJ, Gupta R, et al. GDNF-transfected macrophages produce potent neuroprotective effects in Parkinson’s disease mouse model. PLoS One. 2014;9:e106867.
   PubMed Web of Science ®Google Scholar
• Fabbri M, Paone A, Calore F, et al. MicroRNAs bind to toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA. 2012;109:E2110–E2116.
   PubMed Web of Science ®Google Scholar
• Kim J, Inoue K, Ishii J, et al. A microrna feedback circuit in midbrain dopamine neurons. Science. 2007;317:1220–1224.
   PubMed Web of Science ®Google Scholar
• Thome AD, Harms AS, Volpicelli-Daley LA, et al. microRNA-155 regulates α-synuclein-induced inflammatory responses in models of Parkinson disease. J Neurosci.. 2016;36:2383–2390.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Lu M, Du RH, et al. MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson’s disease. Mol Neurodegener. 2016;11:28.
   PubMed Web of Science ®Google Scholar
• Emmanouilidou E, Melachroinou K, Roumeliotis T, et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci. 2010;30:6838–6851.
   PubMed Web of Science ®Google Scholar
• Rajendran L, Honsho M, Zahn TR, et al. Alzheimer's disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci USA. 2006;103:11172–11177.
   PubMed Web of Science ®Google Scholar
• Trotta T, Panaro MA, Cianciulli A, et al. Microglia-derived extracellular vesicles in Alzheimer's Disease: a double-edged sword. Biochem Pharmacol. 2018;148:184–192.
   PubMed Web of Science ®Google Scholar
• Saman S, Kim W, Raya M, et al. Exosome associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem. 2012;287:3842–3849.
   PubMed Web of Science ®Google Scholar
• Coleman BM, Hanssen E, Lawson VA, et al. Prion-infected cells regulate the release of exosomes with distinct ultrastructural features. FASEB J. 2012;26:4160–4173.
   PubMed Web of Science ®Google Scholar
• Shi M, Liu C, Cook TJ, et al. Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson's disease. Acta Neuropathol. 2014;128:639–650.
   PubMed Web of Science ®Google Scholar
• Stuendl A, Kunadt M, Kruse N, et al. Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies. Brain. 2016;139:481–494.
   PubMed Web of Science ®Google Scholar
• Danzer KM, Kranich LR, Ruf WP, et al. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener. 2012;7:42.
   PubMed Web of Science ®Google Scholar
• Paschon V, Takada SH, Ikebara JM, et al. Interplay between exosomes, microRNAs and Toll-like receptors in brain disorders. Mol Neurobiol. 2016;53:2016–2028.
   PubMed Web of Science ®Google Scholar
• Chang C, Lang H, Geng N, et al. Exosomes of BV-2 cells induced by alpha-synuclein: important mediator of neurodegeneration in PD. Neurosci Lett. 2013;548:190–195.
   PubMed Web of Science ®Google Scholar
• Grey M, Dunning CJ, Gaspar R, et al. Acceleration of α-synuclein aggregation by exosomes. J Biol Chem. 2015;290:2969–2982.
   PubMed Web of Science ®Google Scholar
• Howlett EH, Jensen N, Belmonte F, et al. LRRK2 G2019S-induced mitochondrial DNA damage is LRRK2 kinase dependent and inhibition restores mtDNA integrity in Parkinson's disease. Hum Mol Genet. 2017;26:4340–4351.
   PubMed Web of Science ®Google Scholar
• Steger M, Tonelli F, Ito G, et al. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. Elife. 2016;5:e12813.
   PubMed Web of Science ®Google Scholar
• Tsunemi T, Hamada K, Krainc D. ATP13A2/PARK9 regulates secretion of exosomes and α-synuclein. J Neurosci. 2014;34:15281–15287.
   PubMed Web of Science ®Google Scholar
• Pardridge WM. Drug transport across the blood-brain barrier. J Cereb Blood Flow Metab. 2012;32:1959–1972.
   PubMed Web of Science ®Google Scholar
• Hall J, Prabhakar S, Balaj L, et al. Delivery of therapeutic proteins via extracellular vesicles: review and potential treatments for Parkinson's disease, glioma, and schwannoma. Cell Mol Neurobiol. 2016;36:417–427.
   PubMed Web of Science ®Google Scholar
• Tian Y, Li S, Song J, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014;35:2383–2390.
   PubMed Web of Science ®Google Scholar
• Zhuang X, Xiang X, Grizzle W, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther. 2012;20:239.
   PubMed Web of Science ®Google Scholar
• Trotta T, Panaro MA, Prifti E, et al. Modulation of biological activities in glioblastoma mediated by curcumin. Nutr Cancer. 2019;22:1–13.
   Google Scholar
• Kanada M, Bachmann MH, Hardy JW, et al. Differential fates of biomolecules delivered to target cells via extracellular vesicles. Proc Natl Acad Sci USA. 2015;112:E1433–1442.
   PubMed Web of Science ®Google Scholar
• Ramaswamy S, Soderstrom KE, Kordower JH. Trophic factors therapy in Parkinson's disease. Prog Brain Res. 2009;175:201–216.
   PubMed Web of Science ®Google Scholar
• Yasuhara T, Shingo T, Muraoka K, et al. Neurorescue effects of VEGF on a rat model of Parkinson's disease. Brain Res. 2005;1053:10–18.
   PubMed Web of Science ®Google Scholar
• Qu M, Lin Q, Huang L, et al. Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson's disease. J Controll Release. 2018;287:156–166.
   PubMed Web of Science ®Google Scholar
• Baglio SR, Pegtel DM, Baldini N. Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell free therapy. Front Physiol. 2012;3:359.
   PubMed Web of Science ®Google Scholar
• Jarmalaviciute A, Tunaitis V, Pivoraite U, et al. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis. Cytotherapy. 2015;17:932–939.
   PubMed Web of Science ®Google Scholar
• Gui Y, Liu H, Zhang L, et al. Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease. Oncotarget. 2015;6:37043–37053.
   PubMed Web of Science ®Google Scholar
• Saraiva C, Paiva J, Santos T, et al. MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease. J Control Release. 2016;235:291–305.
   PubMed Web of Science ®Google Scholar
• Choi DC, Chae YJ, Kabaria S, et al. MicroRNA-7 protects against 1-methyl-4-phenylpyridinium-induced cell death by targeting RelA. J Neurosci. 2014;34:12725–12737.
   PubMed Web of Science ®Google Scholar
• Miñones-Moyano E, Porta S, Escaramís G, et al. MicroRNA profiling of Parkinson's disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function. Hum Mol Genet. 2011;20:3067–3078.
   PubMed Web of Science ®Google Scholar
• He Q, Wang Q, Yuan C, et al. Downregulation of miR-7116-5p in microglia by MPP + sensitizes TNF-α production to induce dopaminergic neuron damage. Glia. 2017;65:1251–1263.
   PubMed Web of Science ®Google Scholar
• Cao XY, Lu JM, Zhao ZQ, et al. MicroRNA biomarkers of Parkinson's disease in serum exosome-like microvesicles. Neurosci Lett. 2017;644:94–99.
   PubMed Web of Science ®Google Scholar
• Xin H, Li Y, Buller B, et al. Exosome-mediated transfer of mir-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells. 2012;30:1556–1564.
   PubMed Web of Science ®Google Scholar
• Tavernarakis N, Wang SL, Dorovkov M, et al. Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nat Genet. 2000;24:180–183.
   PubMed Web of Science ®Google Scholar
• Whitehead KA, Dahlman JE, Langer RS, et al. Silencing or stimulation? siRNA delivery and the immune system. Annu Rev Chem Biomol Eng. 2011;2:77–96.
   PubMed Web of Science ®Google Scholar
• Cooper JM, Wiklander PB, Nordin JZ, et al. Systemic exosomal siRNA delivery reduced α-synuclein aggregates in brains of transgenic mice. Mov Disord. 2014;29:1476–1485.
   PubMed Web of Science ®Google Scholar