medigraphic.com
Instituto Nacional de Neurología y Neurocirugía

2018, Number 3

Next >>

Arch Neurocien 2018; 23 (3)

Exosomes and the spread of neurodegenerative diseases

Gómez-Chavarín M, Morales-Gómez MR

Language: Spanish
References: 58
Page: 6-18
PDF size: 959.25 Kb.


ABSTRACT

Recently the abnormal aggregation of protein has been implicated in diseases such as Alzheimer’s and Parkinson’s disease and neurodegenerative disorders. Recent studies have suggested that the transmission of these protein aggregates between neurons, are the underlying mechanism to progress and the pathology of the diseases. However, the precise mechanism which transmits these aggregates between neurons is unknown. They have suggested that the exosomes, a specific group of extracellular vesicles, can participate in the proteins, RNA and DNA transfer between neurons and play an important role in the transmission of aggregates. This manuscript describes various types of vesicles and evidence supporting the role of exosomes in the transmission of aggregates between neurons, as well as their relation to neurodegenerative processes. It also describes some mechanisms involved in transmission mediated by exosomes, how in the case of the exosomes released by nerve cells whose contents have molecular profiles that represent a time of the state of health of the brain, so it can used as biomarkers of the cerebral microenvironment and contribute to the progress of neurodegenerative diseases by facilitating the spread of proteins poorly folded to distant sites. This review also summarizes some studies in exosomes in the pathophysiology of Parkinson’s disease and experimental models, and their potential use as biomarkers of diseases.


REFERENCES

  1. Brettschneider J, Del Tredici K, Lee VM, Trojanowski JQ. Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci. 2015;16(2):109–120.

  2. Jucker M, Walker LC. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature. 2013;501(7465):45–51.

  3. Oueslati A, Ximerakis M, Vekrellis K. Protein transmission, seeding and degradation: key steps for alpha-Synuclein prion-like propagation. Exp Neurobiol. 2014;23(4):324–336.

  4. Brundin P, Melki R, Kopito R. Prion-like transmission of protein aggregates in neurodegenerative diseases. Nat Rev Mol Cell Biol. 2010;11(4):301– 7.

  5. Frost B, Diamond MI. Prion-like mechanisms in neurodegenerative diseases. Nat Rev Neurosci. 2010;11(3):155–159.

  6. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–259

  7. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003;24(2):197–211

  8. Jellinger KA. A critical reappraisal of current staging of Lewy-related pathology in human brain. Acta Neuropathol. 2008;116(1):1–16.

  9. Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson’s disease: The inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837-844.

  10. Schneider JA, Arvanitakis Z, Yu L, Boyle PA, Leurgans SE, Bennett DA. Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies. Brain. 2012;135(10):3005-14.

  11. Tofaris GK. Lysosome-dependent pathways as a unifying theme in Parkinson’s disease. Mov Disord. 2012;27(11):1364-9.

  12. Perrett RM, Alexopoulou Z, Tofaris GK. The endosomal pathway in Parkinson’s disease. Mol Cell Neurosci. 2015;66(A):21-28.

  13. Lee SJ, Desplats P, Sigurdson C, Tsigelny I, Masliah E. Cell-to-cell transmission of non-prion protein aggregates. Nat Rev Neurol. 2010;6(12):702–6.

  14. Lee SJ, Lim HS, Masliah E, Lee HJ. Protein aggregate spreading in neurodegenerative diseases: problems and perspectives. Neurosci Res. 2011,70(4):339–48.

  15. Abrahamsen H, Stenmark H. Protein secretion: unconventional exit by exophagy. Curr Biol. 2010;20(9):R415–18.

  16. Ejlerskov P, Rasmussen I, Nielsen TT, Bergstrom AL, Tohyama Y, Jensen PH, Vilhardt F. Tubulin polymerizationpromoting protein (TPPP/p25 alpha) promotes unconventional secretion of alpha-Synuclein through Exophagy by impairing Autophagosome-lysosome fusion. J Biol Chem. 2013;288(24):17313–35.

  17. Kim W, Lee S, Jung C, Ahmed A, Lee G, Hall GF. Interneuronal transfer of human tau between lamprey central neurons in situ. J Alzheimers Dis. 2010;19(2):647–64.

  18. Lee HJ, Patel S, Lee SJ. Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci. 2005;25(25):6016–24.

  19. Lee JG, Takahama S, Zhang G, Tomarev SI, Ye Y. Unconventional secretion of misfolded proteins promotes adaptation to proteasome dysfunction in mammalian cells. Nat Cell Biol. 2016;18(7):765–76.

  20. Oueslati A, Ximerakis M, Vekrellis K. Protein transmission, seeding and degradation: key steps for alpha-Synuclein prion-like propagation. Exp Neurobiol. 2014;23(4):324–36.

  21. Volkmar N, Fenech E, Christianson JC. New MAPS for misfolded proteins. Nat Cell Biol. 2016;18(7):724–26.

  22. Busche MA, Grienberger C, Keskin AD, Song B, Neumann U, Staufenbiel M, Forstl H, Konnerth A. Decreased amyloid-beta and increased neuronal hyperactivity by immunotherapy in Alzheimer's models. Nat Neurosci. 2015;18(12):1725–27.

  23. Kim C, Ho DH, Suk JE, You S, Michael S, Kang J, Joong Lee S, Masliah E, Hwang D, Lee HJ, Lee SJ. Neuron-released oligomeric alpha-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat Commun. 2013;4:1562.

  24. Gyorgy B, Szabo TG, Pasztoi M, Pal Z, Misjak P, Aradi B, Laszlo V, Pallinger E, Pap E, Kittel A, Nagy G, Falus A, Buzas EI. Membrane vesicles, current state of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci. 2011;68(16):2667–88.

  25. Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteome. 2010;73(10):1907–20.

  26. EL Andaloussi, Mager I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12(5):347–57.

  27. Simons M, Raposo G. Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009;21(4):575–81.

  28. Simpson RJ, Jensen SS, Lim JW. Proteomic profiling of exosomes: current perspectives. Proteomics. 2008;8(19):4083–99

  29. Marzesco AM, Janich P, Wilsch-Brauninger M, Dubreuil V, Langenfeld K, Corbeil D, Huttner WB. Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells. J Cell Sci. 2005;118(Pt 13):2849–58.

  30. Mora EM, Alvarez-Cubela S, Oltra E. Biobanking of Exosomes in the era of precision medicine: are we there yet? Int J Mol Sci. 2015;17(1).

  31. Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colas E, Cordeiro-da Silva A, Fais S, Falcon- Perez JM, Ghobrial IM, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard NH, Hendrix A, Kierulf P, Kokubun K, et.al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066.

  32. Ludwig AK, Giebel B. Exosomes: small vesicles participating in intercellular communication. Int J Biochem Cell Biol. 2012;44(1):11–15.

  33. Thery C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006; 3(3):22.

  34. Witwer KW, Buzas EI, Bemis LT, Bora A, Lasser C, Lotvall J, Nolte-'t Hoen EN, Piper MG, Sivaraman S, Skog J, Thery C, Wauben MH, Hochberg F. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles. 2013;2:13-15.

  35. Colombo M, Raposo G, Théry C Biogenesis, secretion and intracellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30, 255-89.

  36. Kowal J, Arras G, Colombo M, Jouve M, Morath JP, 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 U S A. 2016;113(8);E968-E977.

  37. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, W¨urdinger T, Middeldorp JM. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A. 2010;107(14),6328-33.

  38. Alvarez-Erviti L, SeowY,Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29(4): 341-45.

  39. Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, Raposo G. Cells release prions in association with exosomes. Proc Natl Acad Sci USA. 2004; 101(26):9683–9688.

  40. Rajendran L, Honsho M, Zahn TR, Keller P, Geiger KD, Verkade P, Simons K. Alzheimer's disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci USA. 2006;103(30):11172–77.

  41. Dinkins MB, Dasgupta S, Wang G, Zhu G, Bieberich E. Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease. Neurobiol Aging. 2014;35(8):1792–1800.

  42. Saman S, Kim W, Raya M, Visnick Y, Miro S, Saman S, Jackson B, McKee AC, Alvarez VE, Lee NC, Hall GF. Exosomeassociated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J Biol Chem. 2012;287(6):3842–49.

  43. Wang Y, Balaji V, Kaniyappan S, Kruger L, Irsen S, Tepper K, Chandupatla R, Maetzler W, Schneider A, Mandelkow E, Mandelkow EM. The release and trans-synaptic transmission of tau via exosomes. Mol Neurodegener. 2017;12(1): 5.

  44. Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T, Wolozin B, Butovsky O, Kugler S, Ikezu T. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci. 2015;18(11):1584–93.

  45. Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, Stefanis L, Vekrellis K. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci. 2010;30(20):6838–6851.

  46. Delenclos M, Trendafilova T, Mahesh D, Baine AM, Moussaud S, Yan IK, Patel T, McLean PJ. Investigation of Endocytic pathways for the internalization of exosome-associated Oligomeric alpha-Synuclein. Front Neurosci. 2017;11:172.

  47. Alvarez-Erviti L, Seow Y, Schapira AH, Gardiner C, Sargent IL, Wood MJ, Cooper JM: Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol Dis. 2011;42(3):360–7.

  48. Danzer KM, Kranich LR, Ruf WP, Cagsal-Getkin O, Winslow AR, Zhu L, Vanderburg CR, McLean PJ. Exosomal cell-tocell transmission of alpha synuclein oligomers. Mol Neurodegener. 2012;7:42.

  49. 49. Stuendl A, Kunadt M, Kruse N, Bartels C, Moebius W, Danzer KM, Mollenhauer B, Schneider A. Induction of alpha-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies. Brain. 2016;139(2):481–94.

  50. Ngolab J, Trinh I, Rockenstein E, Mante M, Florio J, Trejo M, Masliah D, Adame A, Masliah E, Rissman RA. Brainderived exosomes from dementia with Lewy bodies propagate alpha-synuclein pathology. Acta Neuropathol Commun. 2017;5(1):46.

  51. Grey M, Dunning CJ, Gaspar R, Grey C, Brundin P, Sparr E, Linse S. Acceleration of alpha-synuclein aggregation by exosomes. J Biol Chem. 2015;290(5):2969–82.

  52. Yuyama K, Yamamoto N, Yanagisawa K. Accelerated release of exosome-associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1-induced amyloid fibril formation. J Neurochem. 2008;105(1):217–24.

  53. Hasegawa T, Konno M, Baba T, Sugeno N, Kikuchi A, Kobayashi M, Miura E, Tanaka N, Tamai K, Furukawa K, Arai H, Mori F, Wakabayashi K, Aoki M, Itoyama Y, Takeda A. The AAA-ATPase VPS4 regulates extracellular secretion and lysosomal targeting of alpha-synuclein. PLoS One. 2011;6(12):e29460.

  54. Yamazaki T, Koo EH, Selkoe DJ. Trafficking of cell-surface amyloid beta protein precursor. II. Endocytosis, recycling and lysosomal targeting detected by immunolocalization. J Cell Sci. 1996;109(5):999–1008.

  55. Volkmar N, Fenech E, Christianson JC. New MAPS for misfolded proteins. Nat Cell Biol. 2016;18(7):724–26.

  56. Abounit S, Bousset L, Loria F, Zhu S, de Chaumont F, Pieri L, Olivo-Marin JC, Melki R, Zurzolo C. Tunneling nanotubes spread fibrillar α-synuclein by intercellular trafficking of lysosomes. EMBO J. 2016;35(19):2120-38.

  57. Victoria GS, Zurzolo C. The spread of prion-like proteins by lysosomes and tunneling nanotubes: implications for neurodegenerative diseases. J Cell Biol. 2017; 216(9):2633-44

  58. Davis DM, Sowinski S. Membrane nanotubes: dynamic long-distance connections between animal cells. Nat Rev Mol Cell Biol. 2008;9(6):431–36.




2020     |     www.medigraphic.com