Study of Exosomes Shed New Light on Physiology of Amyloidogenesis

Cellular and Molecular Neurobiology

Volumn 36, Issue 3, 2016, Pages 327-342

  van Niel, Guillaume ^a,b  

^a INSTITUT CURIE   (France)

^b CNRS   (France)

Author keywords

Alzheimer; Amyloid; ApoE; A ; Endosomes; Exosomes; Intraluminal vesicles; MVB; Pigmented cells; PMEL

Indexed keywords

AMYLOID; AMYLOID BETA PROTEIN; APOLIPOPROTEIN E; PREMELANOSOME PROTEIN; TUMOR PROTEIN; UNCLASSIFIED DRUG; MELANIN;

AMYLOID PLAQUE; ARTICLE; CELL FUNCTION; CELL MIGRATION; CELL SELECTION; CELL SURFACE; DEGENERATIVE DISEASE; ENDOSOME; EXOSOME; EXTRACELLULAR MATRIX; HUMAN; MELANOGENESIS; MELANOSOME; NONHUMAN; PATHOGENESIS; PIGMENT CELL; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN CLEAVAGE; PROTEIN STRUCTURE; ANIMAL; BIOSYNTHESIS; METABOLISM;

AMYLOID; AMYLOID BETA-PEPTIDES; ANIMALS; APOLIPOPROTEINS E; ENDOSOMES; EXOSOMES; HUMANS; MELANINS;

EID: 84961209153     PISSN: 02724340     EISSN: 15736830     Source Type: Journal    
DOI: 10.1007/s10571-016-0357-0     Document Type: Article

References (161)

1. Abdul-Hay SO, Sahara T, McBride M, Kang D, Leissring MA (2012) Identification of BACE2 as an avid ß-amyloid-degrading protease. Mol Neurodegener 7:46. doi:10.1186/1750-1326-1187-1146
2. Abels ER, Breakefield XO (2015) Introduction into extracellular vesicles—biogenesis, secretion, uptake and RNA cargo loading. Cell Mol Neurobiol (in press)
3. Adema GJ, de Boer AJ, Vogel AM, Loenen WAM, Figdor CG (1994) Molecular characterization of the melanocyte lineage-specific antigen gp100. J Biol Chem 269:20126–20133
4. Aguzzi A, Rajendran L (2009) The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron 64(6):783–790. doi:10.1016/j.neuron.2009.12.016
5. Almeida CG, Takahashi RH, Gouras GK (2006) Beta-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system. J Neurosci 26:4277–4288. doi:10.1523/JNEUROSCI.5078-05.2006
6. Alvarez-Erviti L, Seow Y, Schapira AH, Gardiner C, Sargent IL, Wood MJ, Cooper JM (2011a) Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol Dis 42(3):360–367. doi:10.1016/j.nbd.2011.01.029
7. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011b) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29(4):341–345. doi:10.1038/nbt.1807
8. An K, Klyubin I, Kim Y, Jung JH, Mably AJ, O’Dowd ST, Lynch T, Kanmert D, Lemere CA, Finan GM, Park JW, Kim TW, Walsh DM, Rowan MJ, Kim JH (2013) Exosomes neutralize synaptic-plasticity-disrupting activity of Aβ assemblies in vivo. Mol Brain 6:47. doi:10.1186/1756-6606-6-47
9. Babst M (2011) MVB vesicle formation: ESCRT-dependent, ESCRT-independent and everything in between. Curr Opin Cell Biol 23(4):452–457. doi:10.1016/j.ceb.2011.04.008
10. Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G (2012) Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14:677–685
11. Bellingham SA, Guo BB, Coleman BM, Hill AF (2012) Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front Physiol 3:124. doi:10.3389/fphys.2012.00124
12. Benilova I, Karran E, De Strooper B (2012) The toxic Abeta oligomer and Alzheimer’s disease: an emperor in need of clothes. Nat Neurosci 15:349–357. doi:10.1038/nn.3028
13. Berson JF, Harper DC, Tenza D, Raposo G, Marks MS (2001) Pmel17 initiates premelanosome morphogenesis within multivesicular bodies. Mol Biol Cell 12(11):3451–3464
14. Berson JF, Theos AC, Harper DC, Tenza D, Raposo G, Marks MS (2003) Proprotein convertase cleavage liberates a fibrillogenic fragment of a resident glycoprotein to initiate melanosome biogenesis. J Cell Biol 161(3):521–533
15. Brouwers JF, Aalberts M, Jansen JW, van Niel G, Wauben MH, Stout TA, Helms JB, Stoorvogel W (2013) Distinct lipid compositions of two types of human prostasomes. Proteomics 13(10–11):1660–1666. doi:10.1002/pmic.201200348
16. Bu G (2009) Apolipoprotein E and its receptors in Alzheimer’s disease: pathways, pathogenesis and therapy. Nat Rev Neurosci 10(5):333–344. doi:10.1038/nrn2620
17. Bycroft M, Bateman A, Clarke J, Hamill SJ, Sandford R, Thomas RL, Chothia C (1999) The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease. EMBO J 18(2):297–305
18. Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, Fagan AM, Morris JC, Mawuenyega KG, Cruchaga C, Goate AM, Bales KR, Paul SM, Bateman RJ, Holtzman DM (2011) Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci Transl Med 3(89):89ra57. doi:10.1126/scitranslmed.3002156
19. Charrin S, le Naour F, Silvie O, Milhiet PE, Boucheix C, Rubinstein E (2009) Lateral organization of membrane proteins: tetraspanins spin their web. Biochem J 420(2):133–154. doi:10.1042/BJ20082422
20. Chia PZ, Toh WH, Sharples R, Gasnereau I, Hill AF, Gleeson PA (2013) Intracellular itinerary of internalised β-secretase, BACE1, and its potential impact on β-amyloid peptide biogenesis. Traffic 14(9):997–1013. doi:10.1111/tra.12088
21. Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M, Elortza F, Lu SC, Mato JM, Falcon-Perez JM (2008) Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 7(12):5157–5166
22. D’Andrea MR, Nagele RG, Wang HY, Peterson PA, Lee DH (2001) Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer’s disease. Histopathology 38:120–134
23. Delevoye C, Giordano F, van Niel G, Raposo G (2011) Biogenesis of melanosomes—the chessboard of pigmentation. Med Sci 27(2):153–162. doi:10.1051/medsci/2011272153
24. Dias V, Junn E, Mouradian MM (2013) The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis 3(4):461–491. doi:10.3233/JPD-130230
25. Dinkins MB, Dasgupta S, Wang G, Zhu G, Bieberich E (2014) Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer’s disease. Neurobiol Aging 35(8):1792–1800. doi:10.1016/j.neurobiolaging.2014.02.012
26. Doens D, Fernandez PL (2014) Microglia receptors and their implications in the response to amyloid beta for Alzheimer’s disease pathogenesis. J Neuroinflammation 11:48. doi:10.1186/1742-2094-1111-1148
27. Dominguez D, Tournoy J, Hartmann D, Huth T, Cryns K, Deforce S, Serneels L, Camacho IE, Marjaux E, Craessaerts K, Roebroek AJ, Schwake M, D’Hooge R, Bach P, Kalinke U, Moechars D, Alzheimer C, Reiss K, Saftig P, De Strooper B (2005) Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice. J Biol Chem 280(35):30797–30806
28. Edgar JR, Willen K, Gouras GK, Futter CE (2015) ESCRTs regulate amyloid precursor protein sorting in multivesicular bodies and intracellular amyloid-beta accumulation. J Cell Sci 128:2520–2528. doi:10.1242/jcs.170233
29. Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, Stefanis L, Vekrellis K (2010) Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 30(20):6838–6851. doi:10.1523/JNEUROSCI.5699-09.2010
30. Esterházy D, Stützer I, Wang H, Rechsteiner MP, Beauchamp J, Döbeli H, Hilpert H, Matile H, Prummer M, Schmidt A, Lieske N, Boehm B, Marselli L, Bosco D, Kerr-Conte J, Aebersold R, Spinas GA, Moch H, Migliorini C, Stoffel M (2011) Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass. Cell Metab 14(3):365–377. doi:10.1016/j.cmet.2011.06.018
31. Fagan AM, Holtzman DM, Munson G, Mathur T, Schneider D, Chang LK, Getz GS, Reardon CA, Lukens J, Shah JA, LaDu MJ (1999) Unique lipoproteins secreted by primary astrocytes from wild type, apoE (−/−), and human apoE transgenic mice. J Biol Chem 274(42):30001–30007
32. Ferreira ST, Vieira MN, De Felice FG (2007) Soluble protein oligomers as emerging toxins in Alzheimer’s and other amyloid diseases. IUBMB Life 59:332–345. doi:10.1080/15216540701283882
33. Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, Raposo G (2004) Cells release prions in association with exosomes. Proc Natl Acad Sci USA 101(26):9683–9688. doi:10.1073/pnas.0308413101
34. Finder VH, Glockshuber R (2007) Amyloid-beta aggregation. Neurodegener Dis 4:13–27. doi:10.1159/000100355
35. Fowler DM, Koulov AV, Alory-Jost C, Marks MS, Balch WE, Kelly JW (2006) Functional amyloid formation within mammalian tissue. PLoS Biol 4(1):e6
36. Fowler DM, Koulov AV, Balch WE, Kelly JW (2007) Functional amyloid—from bacteria to humans. Trends Biochem 32:217–224. doi:10.1016/j.tibs.2007.03.003
37. Friedrich RP, Tepper K, Rönicke R, Soom M, Westermann M, Reymann K, Kaether C, Fändrich M (2010) Mechanism of amyloid plaque formation suggests an intracellular basis of Abeta pathogenicity. Proc Natl Acad Sci USA 107(5):1942–1947. doi:10.1073/pnas.0904532106
38. Garai K, Verghese PB, Baban B, Holtzman DM, Frieden C (2014) The binding of apolipoprotein E to oligomers and fibrils of amyloid-beta alters the kinetics of amyloid aggregation. Biochemistry 53:6323–6331. doi:10.1021/bi5008172
39. Gorman PM, Yip CM, Fraser PE, Chakrabartty A (2003) Alternate aggregation pathways of the Alzheimer beta-amyloid peptide: Abeta association kinetics at endosomal pH. J Mol Biol 325:743–757
40. Gowrishankar S, Yuan P, Wu Y, Schrag M, Paradise S, Grutzendler J, De Camilli P, Ferguson SM (2015) Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer’s disease amyloid plaques. Proc Natl Acad Sci USA 112(28):E3699–E3708. doi:10.1073/pnas.1510329112
41. Greenwald J, Riek R (2010) Biology of amyloid: structure, function, and regulation. Structure 18:1244–1260
42. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8:101–112
43. Hammer ND, Wang X, McGuffie BA, Chapman MR (2008) Amyloids: friend or foe? J Alzheimers Dis 13:407–419
44. Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, Patel T, Piroyan A, Sokolsky M, Kabanov AV, Batrakova EV (2015) Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 207:18–30. doi:10.1016/j.jconrel.2015.1003.1033
45. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356. doi:10.1126/science.1072994
46. Harper DC, Theos AC, Herman KE, Tenza D, Raposo G, Marks MS (2008) Premelanosome amyloid-like fibrils are composed of only golgi-processed forms of Pmel17 that have been proteolytically processed in endosomes. J Biol Chem 283(4):2307–2322
47. Hellström AR, Watt B, Fard SS, Tenza D, Mannström P, Narfström K, Ekesten B, Ito S, Wakamatsu K, Larsson J, Ulfendahl M, Kullander K, Raposo G, Kerje S, Hallböök F, Marks MS, Andersson L (2011) Inactivation of Pmel alters melanosome shape but has only a subtle effect on visible pigmentation. PLoS Genet 7(9):e1002285. doi:10.1371/journal.pgen.1002285
48. Ho T, Watt B, Spruce LA, Seeholzer SH, Marks MS (2016) The kringle-like domain facilitates post-endoplasmic reticulum changes to premelanosome protein (PMEL) oligomerization and disulfide bond configuration and promotes amyloid formation. J Biol Chem 291(7):3595–3612
49. Hoashi T, Muller J, Vieira WD, Rouzaud F, Kikuchi K, Tamaki K, Hearing VJ (2006) The repeat domain of the melanosomal matrix protein PMEL17/GP100 is required for the formation of organellar fibers. J Biol Chem 281(30):21198–21208
50. Holtzman DM, Herz J, Bu G (2012) Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006312. doi:10.1101/cshperspect.a006312
51. Hori Y, Hashimoto T, Nomoto H, Hyman BT, Iwatsubo T (2015) Role of apolipoprotein E in beta-amyloidogenesis: isoform-specific effects on protofibril to fibril conversion of Abeta in vitro and brain Abeta deposition in vivo. J Biol Chem 290:15163–15174. doi:10.1074/jbc.M114.622209
52. Hu X, Crick SL, Bu G, Frieden C, Pappu RV, Lee JM (2009) Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. Proc Natl Acad Sci USA 106(48):20324–20329. doi:10.1073/pnas.0911281106
53. Hurbain I, Geerts WJ, Boudier T, Marco S, Verkleij AJ, Marks MS, Raposo G (2008) Electron tomography of early melanosomes: implications for melanogenesis and the generation of fibrillar amyloid sheets. Proc Natl Acad Sci USA 105(50):19726–19731. doi:10.1073/pnas.0803488105
54. Ihara Y, Morishima-Kawashima M, Nixon R (2012) The ubiquitin-proteasome system and the autophagic-lysosomal system in Alzheimer disease. Cold Spring Harb Perspect Med. doi:10.1101/cshperspect.a006361
55. Ishida BY, Bailey KR, Duncan KG, Chalkley RJ, Burlingame AL, Kane JP, Schwartz DM (2004) Regulated expression of apolipoprotein E by human retinal pigment epithelial cells. J Lipid Res 45(2):263–271
56. Ji ZS, Müllendorff K, Cheng IH, Miranda RD, Huang Y, Mahley RW (2006) Reactivity of apolipoprotein E4 and amyloid beta peptide: lysosomal stability and neurodegeneration. J Biol Chem 281(5):2683–2692
57. Jiang Z, Lee JC (2014) Lysophospholipid-containing membranes modulate the fibril formation of the repeat domain of a human functional amyloid, pmel17. J Mol Biol 426(24):4074–4086. doi:10.1016/j.jmb.2014.10.009
58. Jiang Q, Lee CY, Mandrekar S, Wilkinson B, Cramer P, Zelcer N, Mann K, Lamb B, Willson TM, Collins JL, Richardson JC, Smith JD, Comery TA, Riddell D, Holtzman DM, Tontonoz P, Landreth GE (2008) ApoE promotes the proteolytic degradation of Abeta. Neuron 58(5):681–693. doi:10.1016/j.neuron.2008.04.010
59. Johnson LV, Forest DL, Banna CD, Radeke CM, Maloney MA, Hu J, Spencer CN, Walker AM, Tsie MS, Bok D, Radeke MJ, Anderson DH (2011) Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration. Proc Natl Acad Sci USA 108(45):18277–18282. doi:10.1073/pnas.1109703108
60. Jovic M, Sharma M, Rahajeng J, Caplan S (2010) The early endosome: a busy sorting station for proteins at the crossroads. Histol Histopathol 25:99–112
61. Kandalepas PC, Sadleir KR, Eimer WA, Zhao J, Nicholson DA, Vassar R (2013) The Alzheimer’s β-secretase BACE1 localizes to normal presynaptic terminals and to dystrophic presynaptic terminals surrounding amyloid plaques. Acta Neuropathol 126(3):329–352. doi:10.1007/s00401-013-1152-3
62. Kanekiyo T, Bu G (2014) The low-density lipoprotein receptor-related protein 1 and amyloid-beta clearance in Alzheimer’s disease. Front Aging Neurosci 6:93. doi:10.3389/fnagi.2014.00093
63. Kanekiyo T, Xu H, Bu G (2014) ApoE and Abeta in Alzheimer’s disease: accidental encounters or partners? Neuron 81:740–754. doi:10.1016/j.neuron.2014.01.045
64. Karlsson O, Lindquist NG (2013) Melanin affinity and its possible role in neurodegeneration. J Neurol Transm 120:1623–1630. doi:10.1007/s00702-013-1062-5
65. Kawaguchi M, Hozumi Y, Suzuki T (2015) ADAM protease inhibitors reduce melanogenesis by regulating PMEL17 processing in human melanocytes. J Dermatol Sci 78:133–142. doi:10.1016/j.jdermsci.2015.02.020
66. Kimura N, Yanagisawa K (2007) Endosomal accumulation of GM1 ganglioside-bound amyloid beta-protein in neurons of aged monkey brains. Neuroreport 18:1669–1673. doi:10.1097/WNR.0b013e3282f0d2ab
67. Kockx M, Jessup W, Kritharides L (2008) Regulation of endogenous apolipoprotein E secretion by macrophages. Arterioscler Thromb Vasc Biol 28(6):1060–1067. doi:10.1161/ATVBAHA.108.164350
68. Krämer-Albers EM, Bretz N, Tenzer S, Winterstein C, Möbius W, Berger H, Nave KA, Schild H, Trotter J (2007) Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: trophic support for axons? Proteomics Clin 1(11):1446–1461
69. Kummer MP, Maruyama H, Huelsmann C, Baches S, Weggen S, Koo EH (2009) Formation of Pmel17 amyloid is regulated by juxtamembrane metalloproteinase cleavage, and the resulting C-terminal fragment is a substrate for gamma-secretase. J Biol Chem 284(4):2296–2306. doi:10.1074/jbc.M808904200
70. Kushimoto T, Basrur V, Valencia J, Matsunaga J, Vieira WD, Ferrans VJ, Muller J, Appella E, Hearing VJ (2001) A model for melanosome biogenesis based on the purification and analysis of early melanosomes. Proc Natl Acad Sci USA 98(19):10698–10703
71. Kwon BS, Halaban R, Kim GS, Usack L, Pomerantz S, Haq AK (1987) A melanocyte-specific complementary DNA clone whose expression is inducible by melanotropin and isobutylmethyl xanthine. Mol Biol Med 4(6):339–355
72. Lednev IK (2014) Amyloid fibrils: the eighth wonder of the world in protein folding and aggregation. Biophys J 106:1433–1435. doi:10.1016/j.bpj.2014.12.007
73. Lee CY, Tse W, Smith JD, Landreth GE (2012) Apolipoprotein E promotes beta-amyloid trafficking and degradation by modulating microglial cholesterol levels. J Biol Chem 287:2032–2044. doi:10.1074/jbc.M2111.295451
74. Lee MJ, Lee JH, Rubinsztein DC (2013) Tau degradation: the ubiquitin-proteasome system versus the autophagy-lysosome system. Prog Neurobiol 105:49–59. doi:10.1016/j.pneurobio.2013.03.001
75. Leonhardt RM, Vigneron N, Rahner C, Van den Eynde BJ, Cresswell P (2010) Endoplasmic reticulum (ER)-export, subcellular distribution and fibril formation by PMEL17 requires an intact N-terminal domain junction. J Biol Chem 285(21):16166–16683
76. Leonhardt RM, Vigneron N, Rahner C, Cresswell P (2011) Proprotein convertases process Pmel17 during secretion. J Biol Chem 286(11):9321–9337. doi:10.1074/jbc.M110.168088
77. Leonhardt RM, Vigneron N, Hee JS, Graham M, Cresswell P (2013) Critical residues in the PMEL/Pmel17N-terminus direct the hierarchical assembly of melanosomal fibrils. Mol Biol Cell 24(7):964–981. doi:10.1091/mbc.E12-10-0742
78. Li J, Kanekiyo T, Shinohara M, Zhang Y, LaDu MJ, Xu H, Bu G (2012) Differential regulation of amyloid-β endocytic trafficking and lysosomal degradation by apolipoprotein E isoforms. J Biol Chem 287(53):44593–44601. doi:10.1074/jbc.M112.420224
79. Liu P, Reed MN, Kotilinek LA, Grant MK, Forster CL, Qiang W, Shapiro SL, Reichl JH, Chiang AC, Jankowsky JL, Wilmot CM, Cleary JP, Zahs KR, Ashe KH (2015) Quaternary structure defines a large class of amyloid-β oligomers neutralized by sequestration. Cell Rep 11(11):1760–1771. doi:10.1016/j.celrep.2015.05.021
80. Lo Cicero A, Stahl PD, Raposo G (2015) Extracellular vesicles shuffling intercellular messages: for good or for bad. Curr Opin Cell Biol 35:69–77. doi:10.1016/j.ceb.2015.04.013
81. Lopes VS, Wasmeier C, Seabra MC, Futter CE (2007) Melanosome maturation defect in Rab38-deficient retinal pigment epithelium results in instability of immature melanosomes during transient melanogenesis. Mol Biol Cell 18(10):3914–3927
82. Luzio JP, Hackmann Y, Dieckmann NM, Griffiths GM (2014) The biogenesis of lysosomes and lysosome-related organelles. Cold Spring Harb Perspect Med 6:a016840. doi:10.1101/cshperspect.a016840
83. Ly S, Altman R, Petrlova J, Lin Y, Hilt S, Huser T, Laurence TA, Voss JC (2013) Binding of apolipoprotein E inhibits the oligomer growth of amyloid-β peptide in solution as determined by fluorescence cross-correlation spectroscopy. J Biol Chem 288(17):11628–11635. doi:10.1074/jbc.M112.411900
84. Ma J, Yee A, Brewer HB, Das S, Potter H (1994) Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature 372:92–94. doi:10.1038/372092a372090
85. Mahley RW, Rall SC (2000) Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1:507–537. doi:10.1146/annurev.genom.1.1.507
86. Maji SK, Perrin MH, Sawaya MR, Jessberger S, Vadodaria K, Rissman RA, Singru PS, Nilsson KP, Simon R, Schubert D, Eisenberg D, Rivier J, Sawchenko P, Vale W, Riek R (2009) Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science 325(5938):328–332. doi:10.1126/science.1173155
87. Maresh GA, Marken JS, Neubauer M, Aruffo A, Hellström I, Hellström KE, Marquardt H (1994a) Cloning and expression of the gene for the melanoma-associated ME20 antigen. DNA Cell Biol 13(2):87–95
88. Maresh GA, Wang WC, Beam KS, Malacko AR, Hellström I, Hellström KE, Marquardt H (1994b) Differential processing and secretion of the melanoma-associated ME20 antigen. Arch Biochem Biophys 311(1):95–102
89. Maxfield FR (2014) Role of endosomes and lysosomes in human disease. Cold Spring Harb Perspect Med 6:a016931. doi:10.1101/cshperspect.a016931
90. McGlinchey RP, Shewmaker F, McPhie P, Monterroso B, Thurber K, Wickner RB (2009) The repeat domain of the melanosome fibril protein Pmel17 forms the amyloid core promoting melanin synthesis. Proc Natl Acad Sci USA 106(33):13731–13736. doi:10.1073/pnas.0906509106
91. Morel E, Chamoun Z, Lasiecka ZM, Chan RB, Williamson RL, Vetanovetz C, Dall’Armi C, Simoes S, Point Du Jour KS, McCabe BD, Small SA, Di Paolo G (2013) Phosphatidylinositol-3-phosphate regulates sorting and processing of amyloid precursor protein through the endosomal system. Nat Commun 4:2250. doi:10.1038/ncomms3250
92. Mulcahy LA, Pink RC, Carter DR (2014) Routes and mechanisms of extracellular vesicle uptake. J Extracell Ves. doi:10.3402/jev.v3.24641
93. Nalivaeva NN, Belyaev ND, Kerridge C, Turner AJ (2014) Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease. Front Aging Neurosci 6:235. doi:10.3389/fnagi.2014.00235
94. Neumann U, Rueeger H, Machauer R, Veenstra SJ, Lueoend RM, Tintelnot-Blomley M, Laue G, Beltz K, Vogg B, Schmid P, Frieauff W, Shimshek DR, Staufenbiel M, Jacobson LH (2015) A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice. Mol Neurodegener 10:44. doi:10.1186/s13024-015-0033-8
95. Nogales E, Scheres SH (2015) Cryo-EM: a unique tool for the visualization of macromolecular complexity. Mol Cell 58(4):677–689. doi:10.1016/j.molcel.2015.02.019
96. Papageorgiou N, Carpenter E, Scally AJ, Tobin DJ (2008) Adult human epidermal melanocytes for neurodegeneration research. Neuroreport 19:1787–1791. doi:10.1097/WNR.0b1013e3283193e82
97. Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, García-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18(6):883–891. doi:10.1038/nm.2753
98. Pencheva N, Tran H, Buss C, Huh D, Drobnjak M, Busam K, Tavazoie SF (2012) Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell 151(5):1068–1082. doi:10.1016/j.cell.2012.10.028
99. Perez-Gonzalez R, Gauthier SA, Kumar A, Levy E (2012) The exosome secretory pathway transports amyloid precursor protein carboxyl-terminal fragments from the cell into the brain extracellular space. J Biol Chem 287:43108–43115. doi:10.1074/jbc.M112.404467
100. Peric A, Annaert W (2015) Early etiology of Alzheimer’s disease: tipping the balance toward autophagy or endosomal dysfunction? Acta Neuropathol 129:363–381. doi:10.1007/s00401-014-1379-7
101. Pfefferkorn CM, McGlinchey RP, Lee JC (2010) Effects of pH on aggregation kinetics of the repeat domain of a functional amyloid, Pmel17. Proc Natl Acad Sci USA 107(50):21447–21452. doi:10.1073/pnas.1006424107
102. Pham CL, Kwan AH, Sunde M (2014) Functional amyloid: widespread in nature, diverse in purpose. Essays Biochem 56:207–219. doi:10.1042/bse0560207
103. Pitas RE, Boyles JK, Lee SH, Hui D, Weisgraber KH (1987) Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B, E(LDL) receptors in the brain. J Biol Chem 262:14352–14360
104. Rajendran L, Annaert W (2012) Membrane trafficking pathways in Alzheimer’s disease. Traffic 13:759–770
105. Rajendran L, Honsho M, Zahn TR, Keller P, Geiger KD, Verkade P, Simons K (2006) Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci USA 103(30):11172–11177
106. Rajendran L, Knobloch M, Geiger KD, Dienel S, Nitsch R, Simons K, Konietzko U (2007) Increased Abeta production leads to intracellular accumulation of Abeta in flotillin-1-positive endosomes. Neurodegener Dis 4(2–3):164–170
107. Rajendran L, Bali J, Barr MM, Court FA, Krämer-Albers E-M, Picou F, Raposo G, van der Vos KE, van Niel G, Wang J, Breakefield XO (2014) Emerging roles of extracellular vesicles in the nervous system. J Neurosci 34(46):15482–15489. doi:10.1523/JNEUROSCI.3258-14.2014
108. Raposo G, Marks MS (2007) Melanosomes–dark organelles enlighten endosomal membrane transport. Nat Rev Mol Cell Biol 8(10):786–797
109. Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383
110. Raposo G, Tenza D, Murphy DM, Berson JF, Marks MS (2001) Distinct protein sorting and localization to premelanosomes, melanosomes, and lysosomes in pigmented melanocytic cells. J Cell Biol 152(4):809–824
111. Rebeck GW, LaDu MJ, Estus S, Bu G, Weeber EJ (2006) The generation and function of soluble apoE receptors in the CNS. Mol Neurodegener 1:15
112. Reyes MG, Faraldi F, Rydman R, Wang CC (2003) Decreased nigral neuromelanin in Alzheimer’s disease. Neurol Res 25(2):179–182
113. Robila V, Ostankovitch M, Altrich-Vanlith ML, Theos AC, Drover S, Marks MS, Restifo N, Engelhard VH (2008) MHC class II presentation of gp100 epitopes in melanoma cells requires the function of conventional endosomes and is influenced by melanosomes. J Immunol 181(11):7843–7852
114. Rochin L, Hurbain I, Serneels L, Fort C, Watt B, Leblanc P, Marks MS, De Strooper B, Raposo G, van Niel G (2013) BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells. Proc Natl Acad Sci USA 110:10658–10663. doi:10.1073/pnas.1220748110
115. Schneider A, Simons M (2013) Exosomes: vesicular carriers for intercellular communication in neurodegenerative disorders. Cell Tissue Res 352:33–47
116. Schraermeyer U (1995) Transport of endocytosed material into melanin granules in cultured choroidal melanocytes of cattle—new insights into the relationship of melanosomes with lysosomes. Pigment Cell Res 8:209–214
117. Schraermeyer U, Dohms M (1996) Detection of a fine lamellar gridwork after degradation of ocular melanin granules by cultured peritoneal macrophages. Pigment Cell Res 9:248–254
118. Schraermeyer U, Peters S, Thumann G, Kociok N, Heimann K (1999) Melanin granules of retinal pigment epithelium are connected with the lysosomal degradation pathway. Exp Eye Res 68:237–245
119. Seiji M, Shimao K, Birbeck MS, Fitzpatrick TB (1963) Subcellular localization of melanin biosynthesis. Ann N Y Acad Sci 100:497–533
120. Serrano-Pozo A, Qian J, Monsell SE, Betensky RA, Hyman BT (2015) APOEε2 is associated with milder clinical and pathological Alzheimer disease. Ann Neurol 77(6):917–929
121. Sharples RA, Vella LJ, Nisbet RM, Naylor R, Perez K, Barnham KJ, Masters CL, Hill AF (2008) Inhibition of gamma-secretase causes increased secretion of amyloid precursor protein C-terminal fragments in association with exosomes. FASEB J 22(5):1469–1478. doi:10.1096/fj.07-9357com
122. Stockley JH, O’Neill C (2007) The proteins BACE1 and BACE2 and beta-secretase activity in normal and Alzheimer’s disease brain. Biochem Soc Trans 35(Pt 3):574–576
123. Stützer I, Selevsek N, Esterházy D, Schmidt A, Aebersold R, Stoffel M (2013) Systematic proteomic analysis identifies β-site amyloid precursor protein cleaving enzyme 2 and 1 (BACE2 and BACE1) substrates in pancreatic β-cells. J Biol Chem 288(15):10536–10547. doi:10.1074/jbc.M112.444703
124. Su Y, Chang PT (2001) Acidic pH promotes the formation of toxic fibrils from beta-amyloid peptide. Brain Res 893:287–291
125. Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, Beal MF, Xu H, Greengard P, Gouras GK (2002) Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol 161(5):1869–1879
126. Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, Axel L, Rusinek H, Nicholson C, Zlokovic BV, Frangione B, Blennow K, Ménard J, Zetterberg H, Wisniewski T, de Leon MJ (2015) Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol 11(8):457–470. doi:10.1038/nrneurol.2015.119
127. Taylor JD, Matthews SJ (2015) New insight into the molecular control of bacterial functional amyloids. Front Cell Infect Microbiol 5:33. doi:10.3389/fcimb.2015.00033
128. Theos AC, Truschel ST, Raposo G, Marks MS (2005) The silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function. Pigment Cell Res 18:322–336
129. Theos AC, Truschel ST, Tenza D, Hurbain I, Harper DC, Berson JF, Thomas PC, Raposo G, Marks MS (2006a) A lumenal domain-dependent pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis. Dev Cell 10(3):343–354
130. Theos AC, Berson JF, Theos SC, Herman KE, Harper DC, Tenza D, Sviderskaya EV, Lamoreux ML, Bennett DC, Raposo G, Marks MS (2006b) Dual loss of ER export and endocytic signals with altered melanosome morphology in the silver mutation of Pmel17. Mol Biol Cell 17(8):3598–3612
131. Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brügger B, Simons M (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247
132. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659
133. Valencia JC, Rouzaud F, Julien S, Chen KG, Passeron T, Yamaguchi Y, Abu-Asab M, Tsokos M, Costin GE, Yamaguchi H, Jenkins LM, Nagashima K, Appella E, Hearing VJ (2007) Sialylated core 1 O-glycans influence the sorting of Pmel17/gp100 and determine its capacity to form fibrils. J Biol Chem 282(15):11266–11280
134. van Bebber F, Hruscha A, Willem M, Schmid B, Haass C (2013) Loss of Bace2 in zebrafish affects melanocyte migration and is distinct from Bace1 knock out phenotypes. J Neurochem 127(4):471–481. doi:10.1111/jnc.12198
135. Van Den Bossche K, Naeyaert JM, Lambert J (2006) The quest for the mechanism of melanin transfer. Traffic 7(7):769–778
136. van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, Marks MS, Rubinstein E, Raposo G (2011) The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev Cell 21(4):708–721. doi:10.1016/j.devcel.2011.08.019
137. van Niel G, Bergam P, Di Cicco A, Hurbain I, Lo Cicero A, Dingli F, Palmulli R, Fort C, Potier MC, Schurgers LJ, Loew D, Levy D, Raposo G (2015) Apolipoprotein E regulates amyloid formation within endosomes of pigment cells. Cell Rep 13(1):43–51. doi:10.1016/j.celrep.2015.1008.1057
138. Vassar R, Kuhn PH, Haass C, Kennedy ME, Rajendran L, Wong PC, Lichtenthaler SF (2014) Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J Neurochem 130(1):4–28. doi:10.1111/jnc.12715
139. Vella LJ, Sharples RA, Nisbet RM, Cappai R, Hill AF (2008) The role of exosomes in the processing of proteins associated with neurodegenerative diseases. Eur Biophys J 37:323–332
140. Verbeek MM, Otte-Holler I, Fransen JA, de Waal RM (2002) Accumulation of the amyloid-beta precursor protein in multivesicular body-like organelles. J Histochem Cytochem 50:681–690
141. Verghese PB, Castellano JM, Garai K, Wang Y, Jiang H, Shah A, Bu G, Frieden C, Holtzman DM (2013) ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions. Proc Natl Acad Sci USA 110(19):E1807–E1816. doi:10.1073/pnas.1220484110
142. Vingtdeux V, Sergeant N, Buee L (2012) Potential contribution of exosomes to the prion-like propagation of lesions in Alzheimer’s disease. Front Physiol 3:229. doi:10.3389/fphys.2012.00229
143. Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH (2009) Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration. PLoS One 4(1):e4160. doi:10.1371/journal.pone.0004160
144. Watt B, van Niel G, Fowler DM, Hurbain I, Luk KC, Stayrook SE, Lemmon MA, Raposo G, Shorter J, Kelly JW, Marks MS (2009) N-terminal domains elicit formation of functional Pmel17 amyloid fibrils. J Biol Chem 284(51):35543–35555. doi:10.1074/jbc.M109.047449
145. Watt B, Tenza D, Lemmon MA, Kerje S, Raposo G, Andersson L, Marks MS (2011) Mutations in or near the transmembrane domain alter PMEL amyloid formation from functional to pathogenic. PLoS Genet 7(9):e1002286. doi:10.1371/journal.pgen.1002286
146. Watt B, van Niel G, Raposo G, Marks MS (2013) PMEL: a pigment cell-specific model for functional amyloid formation. Pigment Cell Mel Res 26:300–315. doi:10.1111/pcmr.12067
147. Whelly S, Johnson S, Powell J, Borchardt C, Hastert MC, Cornwall GA (2012) Nonpathological extracellular amyloid is present during normal epididymal sperm maturation. PLoS One 7(5):e36394. doi:10.1371/journal.pone.0036394
148. Wildsmith KR, Holley M, Savage JC, Skerrett R, Landreth GE (2013) Evidence for impaired amyloid beta clearance in Alzheimer’s disease. Alzheimer’s Res Ther 5:33. doi:10.1186/alzrt1187
149. Xiao Q, Yan P, Ma X, Liu H, Perez R, Zhu A, Gonzales E, Burchett JM, Schuler DR, Cirrito JR, Diwan A, Lee JM (2014) Enhancing astrocytic lysosome biogenesis facilitates Aβ clearance and attenuates amyloid plaque pathogenesis. J Neurosci 34(29):9607–9620. doi:10.1523/JNEUROSCI.3788-13.2014
150. Yaar M, Park HY (2012) Melanocytes: a window into the nervous system. J Invest Derm 132:835–845. doi:10.1038/jid.2011.386
151. Yamazaki T, Chang TY, Haass C, Ihara Y (2001) Accumulation and aggregation of amyloid beta-protein in late endosomes of Niemann-pick type C cells. J Biol Chem 276:4454–4460. doi:10.1074/jbc.M009598200
152. Yanagisawa K (2015) GM1 ganglioside and Alzheimer’s disease. Glycoconjugate J 32:87–91. doi:10.1007/s10719-10015-19579-10715
153. Yang AJ, Chandswangbhuvana D, Margol L, Glabe CG (1998) Loss of endosomal/lysosomal membrane impermeability is an early event in amyloid Abeta1-42 pathogenesis. J Neurosci Res 52:691–698
154. Yang T, Martin P, Fogarty B, Brown A, Schurman K, Phipps R, Yin VP, Lockman P, Bai S (2015) Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res 32(6):2003–2014
155. Yim YI, Park BC, Yadavalli R, Zhao X, Eisenberg E, Greene LE (2015) The multivesicular body is the major internal site of prion conversion. J Cell Sci 128(7):1434–1443. doi:10.1242/jcs.165472
156. Yuyama K, Yamamoto N, Yanagisawa K (2006) Chloroquine-induced endocytic pathway abnormalities: cellular model of GM1 ganglioside-induced Abeta fibrillogenesis in Alzheimer’s disease. FEBS Lett 580:6972–6976. doi:10.1016/j.febslet.2006.11.072
157. Yuyama K, Yamamoto N, Yanagisawa K (2008) Accelerated release of exosome-associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1-induced amyloid fibril formation. J Neurochem 105:217–224. doi:10.1111/j.1471-4159.2007.05128.x
158. Yuyama K, Sun H, Mitsutake S, Igarashi Y (2012) Sphingolipid-modulated exosome secretion promotes the clearance of amyloid-β by microglia. J Biol Chem 287(14):10977–10989. doi:10.1074/jbc.M111.324616
159. Yuyama K, Sun H, Sakai S, Mitsutake S, Okada M, Tahara H, Furukawa J, Fujitani N, Shinohara Y, Igarashi Y (2014) Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J Biol Chem 289(35):24488–24498. doi:10.1074/jbc.M114.577213
160. Yuyama K, Sun H, Usuki S, Sakai S, Hanamatsu H, Mioka T, Kimura N, Okada M, Tahara H, Furukawa J, Fujitani N, Shinohara Y, Igarashi Y (2015) A potential function for neuronal exosomes: sequestering intracerebral amyloid-β peptide. FEBS Lett 589(1):84–88. doi:10.1016/j.febslet.2014.11.027
161. Zucca FA, Basso E, Cupaioli FA, Ferrari E, Sulzer D, Casella L, Zecca L (2014) Neuromelanin of the human substantia nigra: an update. Neurotox Res 25(1):13–23. doi:10.1007/s12640-013-9435-y