{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:01:03Z","timestamp":1790715663268,"version":"4.1.0"},"reference-count":148,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T00:00:00Z","timestamp":1528934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The mechanism of intercellular transmission of pathological agents in neurodegenerative diseases has received much recent attention. Huntington\u2019s disease (HD) is caused by a monogenic mutation in the gene encoding Huntingtin (HTT). Mutant HTT (mHTT) harbors a CAG repeat extension which encodes an abnormally long polyglutamine (polyQ) repeat at HTT\u2019s N-terminus. Neuronal pathology in HD is largely due to the toxic gain-of-function by mHTT and its proteolytic products, which forms both nuclear and cytoplasmic aggregates that perturb nuclear gene transcription, RNA splicing and transport as well cellular membrane dynamics. The neuropathological effects of mHTT have been conventionally thought to be cell-autonomous in nature. Recent findings have, however, indicated that mHTT could be secreted by neurons, or transmitted from one neuronal cell to another via different modes of unconventional secretion, as well as via tunneling nanotubes (TNTs). These modes of transmission allow the intercellular spread of mHTT and its aggregates, thus plausibly promoting neuropathology within proximal neuronal populations and between neurons that are connected within neural circuits. Here, the various possible modes for mHTT\u2019s neuronal cell exit and intercellular transmission are discussed.<\/jats:p>","DOI":"10.3390\/cells7060059","type":"journal-article","created":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T11:06:06Z","timestamp":1528974366000},"page":"59","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Unconventional Secretion and Intercellular Transfer of Mutant Huntingtin"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1925-636X","authenticated-orcid":false,"given":"Bor Luen","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, 117597 Singapore, Singapore"},{"name":"NUS Graduate School for Integrative Sciences and Engineering, 117456 Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/ene.13413","article-title":"Huntington\u2019s disease: A clinical review","volume":"25","author":"McColgan","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref_3","first-page":"383","article-title":"Trinucleotide repeat disorders","volume":"145","year":"2017","journal-title":"Handb. Clin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/ng1095-155","article-title":"Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington\u2019s disease gene homologue","volume":"11","author":"Zeitlin","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/0092-8674(95)90542-1","article-title":"Targeted disruption of the Huntington\u2019s disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes","volume":"81","author":"Nasir","year":"1995","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1126\/science.7618107","article-title":"Inactivation of the mouse Huntington\u2019s disease gene homolog Hdh","volume":"269","author":"Duyao","year":"1995","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/ng1095-115","article-title":"HEAT repeats in the Huntington\u2019s disease protein","volume":"11","author":"Andrade","year":"1995","journal-title":"Nat. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/hmg\/ddp524","article-title":"Huntingtin facilitates polycomb repressive complex 2","volume":"19","author":"Seong","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16889","DOI":"10.1073\/pnas.1420103111","article-title":"Potential function for the Huntingtin protein as a scaffold for selective autophagy","volume":"111","author":"Ochaba","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/ncb3101","article-title":"Huntingtin functions as a scaffold for selective macroautophagy","volume":"17","author":"Rui","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.neuron.2016.02.003","article-title":"The biology of Huntingtin","volume":"89","author":"Saudou","year":"2016","journal-title":"Neuron"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"71","DOI":"10.4161\/cam.3.1.7511","article-title":"Huntingtin associated protein 1 and its functions","volume":"3","author":"Wu","year":"2009","journal-title":"Cell Adhes. Migr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.cellsig.2017.02.023","article-title":"Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins","volume":"35","author":"Mackenzie","year":"2017","journal-title":"Cell Signal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4271","DOI":"10.1111\/j.1742-4658.2008.06563.x","article-title":"Huntington\u2019s disease: Roles of huntingtin-interacting protein 1 (HIP-1) and its molecular partner HIPPI in the regulation of apoptosis and transcription","volume":"275","author":"Bhattacharyya","year":"2008","journal-title":"FEBS J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1074\/jbc.M509806200","article-title":"Interaction of Huntingtin-associated protein-1 with kinesin light chain: Implications in intracellular trafficking in neurons","volume":"281","author":"McGuire","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10045","DOI":"10.1073\/pnas.0610628104","article-title":"Huntingtin facilitates dynein\/dynactin-mediated vesicle transport","volume":"104","author":"Caviston","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6763","DOI":"10.1073\/pnas.100110097","article-title":"The Huntington\u2019s disease protein interacts with p53 and CREB-binding protein and represses transcription","volume":"97","author":"Steffan","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1128\/MCB.22.5.1277-1287.2002","article-title":"Interaction of Huntington disease protein with transcriptional activator Sp1","volume":"22","author":"Li","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/ng1219","article-title":"Huntingtin interacts with REST\/NRSF to modulate the transcription of NRSE-controlled neuronal genes","volume":"35","author":"Zuccato","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.neuron.2010.06.027","article-title":"Huntingtin is required for mitotic spindle orientation and mammalian neurogenesis","volume":"67","author":"Godin","year":"2010","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1172\/JCI57552","article-title":"Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease","volume":"121","author":"Keryer","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ydbio.2015.07.013","article-title":"Huntingtin is required for ciliogenesis and neurogenesis during early Xenopus development","volume":"408","author":"Haremaki","year":"2015","journal-title":"Dev. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.nbd.2015.05.008","article-title":"A novel function of Huntingtin in the cilium and retinal ciliopathy in Huntington\u2019s disease mice","volume":"80","author":"Karam","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1523\/JNEUROSCI.1870-13.2014","article-title":"The regulation of autophagosome dynamics by huntingtin and HAP1 is disrupted by expression of mutant huntingtin, leading to defective cargo degradation","volume":"34","author":"Wong","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14794","DOI":"10.1523\/JNEUROSCI.2774-11.2011","article-title":"Spatial and temporal requirements for huntingtin (Htt) in neuronal migration and survival during brain development","volume":"31","author":"Tong","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8608","DOI":"10.1523\/JNEUROSCI.5110-12.2013","article-title":"Huntingtin mediates anxiety\/depression-related behaviors and hippocampal neurogenesis","volume":"33","author":"Pla","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","article-title":"Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice","volume":"87","author":"Mangiarini","year":"1996","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1073\/pnas.1221891110","article-title":"Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease","volume":"110","author":"Sathasivam","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S1097-2765(02)00602-0","article-title":"Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions","volume":"10","author":"Lunkes","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0014-4886(03)00132-8","article-title":"Huntingtin is degraded to small fragments by calpain after ischemic injury","volume":"183","author":"Kim","year":"2003","journal-title":"Exp. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"20211","DOI":"10.1074\/jbc.M401267200","article-title":"Inhibition of calpain cleavage of huntingtin reduces toxicity: Accumulation of calpain\/caspase fragments in the nucleus","volume":"279","author":"Gafni","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12784","DOI":"10.1073\/pnas.221451398","article-title":"Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington\u2019s disease brains, associate with membranes, and undergo calpain-dependent proteolysis","volume":"98","author":"Kim","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.cell.2006.04.026","article-title":"Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin","volume":"125","author":"Graham","year":"2006","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1093\/hmg\/ddn139","article-title":"Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus","volume":"17","author":"Warby","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.nbd.2005.11.012","article-title":"Lysosomal proteases are involved in generation of N-terminal huntingtin fragments","volume":"22","author":"Kim","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.neuron.2010.06.021","article-title":"Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington\u2019s disease","volume":"67","author":"Miller","year":"2010","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/hmg\/ddi071","article-title":"A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: Evidence for a compact beta-sheet structure","volume":"14","author":"Poirier","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/nchembio.2461","article-title":"A toxic mutant huntingtin species is resistant to selective autophagy","volume":"13","author":"Fu","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1126\/science.aad2033","article-title":"Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA","volume":"351","author":"Woerner","year":"2016","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuron.2017.03.027","article-title":"Polyglutamine-expanded Huntingtin exacerbates age-related disruption of nuclear integrity and nucleocytoplasmic transport","volume":"94","author":"Goginashvili","year":"2017","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1126\/science.1059581","article-title":"Loss of huntingtin-mediated BDNF gene transcription in Huntington\u2019s disease","volume":"293","author":"Zuccato","year":"2001","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.cell.2004.06.018","article-title":"Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules","volume":"118","author":"Gauthier","year":"2004","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6298","DOI":"10.1523\/JNEUROSCI.2033-12.2013","article-title":"Mutant Huntingtin alters retrograde transport of TrkB receptors in striatal dendrites","volume":"33","author":"Liot","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/(SICI)1097-4547(19990915)57:6<782::AID-JNR3>3.0.CO;2-9","article-title":"Rhes: A striatal-specific Ras homolog related to Dexras1","volume":"57","author":"Falk","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1126\/science.1172871","article-title":"Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity","volume":"324","author":"Subramaniam","year":"2009","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.nbd.2015.05.011","article-title":"Ectopic expression of the striatal-enriched GTPase Rhes elicits cerebellar degeneration and an ataxia phenotype in Huntington\u2019s disease","volume":"82","author":"Swarnkar","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"a020628","DOI":"10.1101\/cshperspect.a020628","article-title":"Astrocytes in neurodegenerative disease","volume":"7","author":"Phatnani","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1172\/JCI81134","article-title":"Extracellular vesicles and intercellular communication within the nervous system","volume":"126","author":"Zappulli","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fnmol.2017.00276","article-title":"Extracellular vesicles in brain tumors and neurodegenerative diseases","volume":"10","author":"Ciregia","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1080\/19336896.2016.1223003","article-title":"Tunneling nanotubes: A possible highway in the spreading of tau and other prion-like proteins in neurodegenerative diseases","volume":"10","author":"Abounit","year":"2016","journal-title":"Prion"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1083\/jcb.201701047","article-title":"The spread of prion-like proteins by lysosomes and tunneling nanotubes: Implications for neurodegenerative diseases","volume":"216","author":"Victoria","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/nn.3761","article-title":"Transneuronal propagation of mutant huntingtin contributes to non-cell autonomous pathology in neurons","volume":"17","author":"Rieker","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E5427","DOI":"10.1073\/pnas.1516217112","article-title":"Transcellular spreading of huntingtin aggregates in the Drosophila brain","volume":"112","author":"Babcock","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/mp.2015.81","article-title":"Huntington\u2019s disease cerebrospinal fluid seeds aggregation of mutant huntingtin","volume":"20","author":"Tan","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00401-016-1582-9","article-title":"Human-to-mouse prion-like propagation of mutant huntingtin protein","volume":"132","author":"Jeon","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9000","DOI":"10.1523\/JNEUROSCI.0118-17.2017","article-title":"Mutant huntingtin is secreted via a late endosomal\/lysosomal unconventional secretory pathway","volume":"37","author":"Trajkovic","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_57","first-page":"3678","article-title":"Transfer of polyglutamine aggregates in neuronal cells occurs in tunneling nanotubes","volume":"126","author":"Costanzo","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6768","DOI":"10.1038\/ncomms7768","article-title":"Prion-like transmission of neuronal huntingtin aggregates to phagocytic glia in the Drosophila brain","volume":"6","author":"Pearce","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1074\/jbc.M117.813667","article-title":"The 17-residue-long N terminus in huntingtin controls stepwise aggregation in solution and on membranes via different mechanisms","volume":"293","author":"Pandey","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1089\/ars.2013.5802","article-title":"The ubiquitin-proteasome system in neurodegeneration","volume":"21","author":"McKinnon","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.expneurol.2010.11.003","article-title":"Autophagy and misfolded proteins in neurodegeneration","volume":"238","author":"Metcalf","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1146\/annurev.cellbio.20.010403.105307","article-title":"Bi-directional protein transport between the ER and Golgi","volume":"20","author":"Lee","year":"2004","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1002\/jcp.24082","article-title":"Non-classical membrane trafficking processes galore","volume":"227","author":"Chua","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5251","DOI":"10.1242\/jcs.103630","article-title":"Diversity in unconventional protein secretion","volume":"125","author":"Rabouille","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-4939-3804-9_2","article-title":"Unconventional Protein Secretion in Animal Cells","volume":"1459","author":"Ng","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cruz-Garcia, D., Malhotra, V., and Curwin, A.J. (2018). Unconventional protein secretion triggered by nutrient starvation. Semin. Cell Dev. Biol., S1084-9521(18)30003-X.","DOI":"10.1016\/j.semcdb.2018.02.021"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/tra.12558","article-title":"The biology of extracellular microvesicles","volume":"19","author":"Sedgwick","year":"2018","journal-title":"Traffic"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1126\/science.1093133","article-title":"Nanotubular highways for intercellular organelle transport","volume":"303","author":"Rustom","year":"2004","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"20130505","DOI":"10.1098\/rstb.2013.0505","article-title":"Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of wiring transmission add a new dimension to brain neuro-glial networks","volume":"369","author":"Agnati","year":"2014","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.bbamem.2016.02.011","article-title":"Exosomes and other extracellular vesicles in neural cells and neurodegenerative diseases","volume":"1858","author":"Janas","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"142","DOI":"10.3389\/fnins.2017.00142","article-title":"Exosomes in the diseased brain: First insights from in vivo studies","volume":"11","author":"Levy","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tcb.2015.01.004","article-title":"Ectosomes and exosomes: Shedding the confusion between extracellular vesicles","volume":"25","author":"Cocucci","year":"2015","journal-title":"Trends Cell Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10571-016-0345-4","article-title":"Ciliary Extracellular Vesicles: Txt Msg Organelles","volume":"36","author":"Wang","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mam.2017.12.003","article-title":"Role of extracellular vesicles in glioma progression","volume":"60","author":"Quezada","year":"2018","journal-title":"Mol. Aspects Med."},{"key":"ref_76","first-page":"994","article-title":"Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy","volume":"33","author":"Ahmad","year":"2014","journal-title":"EMBO J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e2467","DOI":"10.1038\/cddis.2016.358","article-title":"Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage","volume":"7","author":"Jiang","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/stem.1835","article-title":"Lysosomal cross-correction by hematopoietic stem cell-derived macrophages via tunneling nanotubes","volume":"33","author":"Naphade","year":"2015","journal-title":"Stem Cells"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.15252\/embj.201593411","article-title":"Tunneling nanotubes spread fibrillar \u03b1-synuclein by intercellular trafficking of lysosomes","volume":"35","author":"Abounit","year":"2016","journal-title":"EMBO J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"a024091","DOI":"10.1101\/cshperspect.a024091","article-title":"Cell biology and pathophysiology of \u03b1-Synuclein","volume":"8","author":"Sharma","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1007\/s00018-016-2411-y","article-title":"Synucleinopathies: Common features and hippocampal manifestations","volume":"74","author":"Yang","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6016","DOI":"10.1523\/JNEUROSCI.0692-05.2005","article-title":"Intravesicular localization and exocytosis of alpha-synuclein and its aggregates","volume":"25","author":"Lee","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1111\/j.1471-4159.2010.06695.x","article-title":"Non-classical exocytosis of alpha-synuclein is sensitive to folding states and promoted under stress conditions","volume":"113","author":"Jang","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6838","DOI":"10.1523\/JNEUROSCI.5699-09.2010","article-title":"Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival","volume":"30","author":"Emmanouilidou","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1750-1326-7-42","article-title":"Exosomal cell-to-cell transmission of alpha synuclein oligomers","volume":"7","author":"Danzer","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"21856","DOI":"10.1074\/jbc.M114.553297","article-title":"The H50Q mutation enhances \u03b1-synuclein aggregation, secretion, and toxicity","volume":"289","author":"Khalaf","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/jnc.12131","article-title":"Activity-dependent secretion of alpha-synuclein by enteric neurons","volume":"125","author":"Paillusson","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/brain\/awv403","article-title":"GABA transmission via ATP-dependent K+ channels regulates \u03b1-synuclein secretion in mouse striatum","volume":"139","author":"Emmanouilidou","year":"2016","journal-title":"Brain"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1038\/emm.2013.45","article-title":"Autophagic failure promotes the exocytosis and intercellular transfer of \u03b1-synuclein","volume":"45","author":"Lee","year":"2013","journal-title":"Exp. Mol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.4161\/auto.36436","article-title":"Autophagy modulates SNCA\/\u03b1-synuclein release, thereby generating a hostile microenvironment","volume":"10","author":"Poehler","year":"2014","journal-title":"Autophagy"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Yang, Y., Qin, M., Bao, P., Xu, W., and Xu, J. (2017). Secretory carrier membrane protein 5 is an autophagy inhibitor that promotes the secretion of \u03b1-synuclein via exosome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180892"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12974-016-0519-5","article-title":"Reciprocal signals between microglia and neurons regulate \u03b1-synuclein secretion by exophagy through a neuronal cJUN-N-terminal kinase-signaling axis","volume":"13","author":"Christensen","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.neurobiolaging.2017.09.016","article-title":"Intercellular transfer of pathogenic \u03b1-synuclein by extracellular vesicles is induced by the lipid peroxidation product 4-hydroxynonenal","volume":"61","author":"Zhang","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.febslet.2013.01.008","article-title":"The secreted oligomeric form of \u03b1-synuclein affects multiple steps of membrane trafficking","volume":"587","author":"Chai","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.nbd.2017.03.007","article-title":"Internalization, axonal transport and release of fibrillar forms of alpha-synuclein","volume":"109","author":"Bieri","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_96","first-page":"324","article-title":"Protein transmission, seeding and degradation: Key steps for \u03b1-Synuclein prion-like propagation","volume":"23","author":"Oueslati","year":"2014","journal-title":"Exp. Meurol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11835","DOI":"10.1523\/JNEUROSCI.0983-17.2017","article-title":"Human astrocytes transfer aggregated alpha-Synuclein via tunneling nanotubes","volume":"37","author":"Rostami","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"11172","DOI":"10.1073\/pnas.0603838103","article-title":"Alzheimer\u2019s disease beta-amyloid peptides are released in association with exosomes","volume":"103","author":"Rajendran","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nrn.2015.1","article-title":"Tau in physiology and pathology","volume":"17","author":"Wang","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000334915","article-title":"Tau overexpression results in its secretion via membrane vesicles","volume":"10","author":"Avila","year":"2012","journal-title":"Neurodegener. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.nbd.2012.05.021","article-title":"Constitutive secretion of tau protein by an unconventional mechanism","volume":"48","author":"Chai","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"10851","DOI":"10.1523\/JNEUROSCI.0387-15.2015","article-title":"C-terminally truncated Forms of Tau, but not full-Length Tau or its C-terminal fragments, are released from neurons independently of cell death","volume":"35","author":"Kanmert","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/embor.2013.15","article-title":"Physiological release of endogenous tau is stimulated by neuronal activity","volume":"14","author":"Pooler","year":"2013","journal-title":"EMBO Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/nn.4328","article-title":"Neuronal activity enhances tau propagation and tau pathology in vivo","volume":"19","author":"Wu","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s40478-016-0386-4","article-title":"Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies","volume":"4","author":"Tardivel","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1750-1326-4-4","article-title":"Insulin-degrading enzyme is exported via an unconventional protein secretion pathway","volume":"4","author":"Zhao","year":"2009","journal-title":"Mol. Neurodegener."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1080\/15548627.2016.1159375","article-title":"Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease","volume":"12","author":"Son","year":"2016","journal-title":"Autophagy"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"37405","DOI":"10.1074\/jbc.M110.149468","article-title":"Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion","volume":"285","author":"Tamboli","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13024-015-0054-3","article-title":"Statins induce insulin-degrading enzyme secretion from astrocytes via an autophagy-based unconventional secretory pathway","volume":"10","author":"Son","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1523\/JNEUROSCI.4253-04.2005","article-title":"Impaired extracellular secretion of mutant superoxide dismutase 1 associates with neurotoxicity in familial amyotrophic lateral sclerosis","volume":"25","author":"Turner","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.neulet.2007.09.024","article-title":"Evidence for secretion of Cu, Zn superoxide dismutase via exosomes from a cell model of amyotrophic lateral sclerosis","volume":"428","author":"Gomes","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Cruz-Garcia, D., Brouwers, N., Duran, J.M., Mora, G., Curwin, A.J., and Malhotra, V. (2017). A diacidic motif determines unconventional secretion of wild-type and ALS-linked mutant SOD1. J. Cell Biol.","DOI":"10.1083\/jcb.201704056"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3620","DOI":"10.1073\/pnas.1312245111","article-title":"Intercellular propagated misfolding of wild-type Cu\/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms","volume":"111","author":"Grad","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1093\/brain\/aww237","article-title":"Exosome secretion is a key pathway for clearance of pathological TDP-43","volume":"139","author":"Iguchi","year":"2016","journal-title":"Brain"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1016\/j.bbadis.2016.07.015","article-title":"Proteomic analysis of FUS interacting proteins provides insights into FUS function and its role in ALS","volume":"1862","author":"Kamelgarn","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1083\/jcb.201504057","article-title":"TDP-43 is intercellularly transmitted across axon terminals","volume":"211","author":"Feiler","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"24178","DOI":"10.18632\/oncotarget.4680","article-title":"Exposure to ALS-FTD-CSF generates TDP-43 aggregates in glioblastoma cells through exosomes and TNTs-like structure","volume":"6","author":"Ding","year":"2015","journal-title":"Oncotarget"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"9683","DOI":"10.1073\/pnas.0308413101","article-title":"Cells release prions in association with exosomes","volume":"101","author":"Fevrier","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/ncb1841","article-title":"Prions hijack tunnelling nanotubes for intercellular spread","volume":"11","author":"Gousset","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Vilette, D., Courte, J., Peyrin, J.M., Coudert, L., Schaeffer, L., Andr\u00e9oletti, O., and Leblanc, P. (2018). Cellular mechanisms responsible for cell-to-cell spreading of prions. Cell. Mol. Life Sci.","DOI":"10.1007\/s00018-018-2823-y"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/ncb1830","article-title":"Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates","volume":"11","author":"Ren","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1172\/JCI80743","article-title":"Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington\u2019s disease patients","volume":"125","author":"Wild","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s10571-016-0350-7","article-title":"Potential transfer of polyglutamine and CAG-repeat RNA in extracellular vesicles in Huntington\u2019s disease: Background and evaluation in cell culture","volume":"36","author":"Zhang","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/ana.24174","article-title":"Mutant huntingtin is present in neuronal grafts in Huntington disease patients","volume":"76","author":"Cicchetti","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.pharmtox.44.101802.121554","article-title":"Identification of the major steps in botulinum toxin action","volume":"44","author":"Simpson","year":"2004","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/j.bbamcr.2016.05.005","article-title":"Transglutaminase type 2-dependent selective recruitment of proteins into exosomes under stressful cellular conditions","volume":"1863","author":"Altuntas","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"9550","DOI":"10.1523\/JNEUROSCI.1418-17.2017","article-title":"Mutant huntingtin inhibits \u03b1B-crystallin expression and impairs exosome secretion from astrocytes","volume":"37","author":"Hong","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1042\/EBC20170024","article-title":"Autophagy\u2019s secret life: Secretion instead of degradation","volume":"61","author":"Jia","year":"2017","journal-title":"Essays Biochem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.cell.2011.07.021","article-title":"Rescue of \u0394F508-CFTR trafficking via a GRASP-dependent unconventional secretion pathway","volume":"146","author":"Gee","year":"2011","journal-title":"Cell"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1083\/jcb.200911154","article-title":"Unconventional secretion of Acb1 is mediated by autophagosomes","volume":"188","author":"Duran","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1083\/jcb.200911149","article-title":"Unconventional secretion of Pichia pastoris Acb1 is dependent on GRASP protein, peroxisomal functions, and autophagosome formation","volume":"188","author":"Manjithaya","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"4701","DOI":"10.1038\/emboj.2011.398","article-title":"Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1\u03b2","volume":"30","author":"Dupont","year":"2011","journal-title":"EMBO J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"650","DOI":"10.4161\/auto.6.5.12066","article-title":"Role of autophagy in unconventional protein secretion","volume":"6","author":"Manjithaya","year":"2010","journal-title":"Autophagy"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3702","DOI":"10.1093\/hmg\/ddq285","article-title":"Early autophagic response in a novel knock-in model of Huntington disease","volume":"19","author":"Heng","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1083\/jcb.201705047","article-title":"Unconventional secretion of FABP4 by endosomes and secretory lysosomes","volume":"217","author":"Villeneuve","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_136","first-page":"359","article-title":"Late steps in secretory lysosome exocytosis in cytotoxic lymphocytes","volume":"4","author":"Zibouche","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/S0962-8924(00)01794-3","article-title":"Regulated secretion of conventional lysosomes","volume":"10","author":"Andrews","year":"2000","journal-title":"Trends Cell Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev.neuro.31.060407.125620","article-title":"The prion\u2019s elusive reason for being","volume":"31","author":"Aguzzi","year":"2008","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1146\/annurev-genet-110711-155524","article-title":"Biology and genetics of prions causing neurodegeneration","volume":"47","author":"Prusiner","year":"2013","journal-title":"Annu. Rev. Genet."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"E5308","DOI":"10.1073\/pnas.1514475112","article-title":"Evidence for \u03b1-synuclein prions causing multiple system atrophy in humans with parkinsonism","volume":"112","author":"Prusiner","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2018.01.015","article-title":"Prion-like seeding and nucleation of intracellular amyloid-\u03b2","volume":"113","author":"Olsson","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.biopsych.2017.04.003","article-title":"Prion-like spreading in tauopathies","volume":"83","author":"Ayers","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"a024463","DOI":"10.1101\/cshperspect.a024463","article-title":"TDP-43 Prions","volume":"8","author":"Nonaka","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"221","DOI":"10.4161\/pri.23807","article-title":"Beta conformation of polyglutamine track revealed by a crystal structure of Huntingtin N-terminal region with insertion of three histidine residues","volume":"7","author":"Kim","year":"2013","journal-title":"Prion"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fnins.2017.00194","article-title":"Exosomes and the Prion protein: More than one truth","volume":"11","author":"Hartmann","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s40478-017-0488-7","article-title":"What is the evidence that tau pathology spreads through prion-like propagation?","volume":"5","author":"Mudher","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.cell.2018.03.005","article-title":"A Huntingtin knockin pig model recapitulates features of selective neurodegeneration in Huntington\u2019s disease","volume":"173","author":"Yan","year":"2018","journal-title":"Cell"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1126\/science.aag3048","article-title":"Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging","volume":"359","author":"Leeman","year":"2018","journal-title":"Science"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/7\/6\/59\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:08:47Z","timestamp":1760195327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/7\/6\/59"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,14]]},"references-count":148,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,6]]}},"alternative-id":["cells7060059"],"URL":"https:\/\/doi.org\/10.3390\/cells7060059","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,14]]}}}