{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:28:27Z","timestamp":1791361707994,"version":"4.3.1"},"reference-count":165,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ABN and Guarantors of Brain and an Irish Institute of Clinical Neuroscience research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disease and is the most common adult motor neuron disease. The disease pathogenesis is complex with the perturbation of multiple pathways proposed, including mitochondrial dysfunction, RNA processing, glutamate excitotoxicity, endoplasmic reticulum stress, protein homeostasis and endosomal transport\/extracellular vesicle (EV) secretion. EVs are nanoscopic membrane-bound particles that are released from cells, involved in the intercellular communication of proteins, lipids and genetic material, and there is increasing evidence of their role in ALS. After discussing the biogenesis of EVs, we review their roles in the propagation of pathological proteins in ALS, such as TDP-43, SOD1 and FUS, and their contribution to disease pathology. We also discuss the ALS related genes which are involved in EV formation and vesicular trafficking, before considering the EV protein and RNA dysregulation found in ALS and how these have been investigated as potential biomarkers. Finally, we highlight the potential use of EVs as therapeutic agents in ALS, in particular EVs derived from mesenchymal stem cells and EVs as drug delivery vectors for potential treatment strategies.<\/jats:p>","DOI":"10.3390\/life13010121","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:12:48Z","timestamp":1672625568000},"page":"121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Extracellular Vesicles in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1008-598X","authenticated-orcid":false,"given":"Gavin","family":"McCluskey","sequence":"first","affiliation":[{"name":"Personalised Medicine Centre, School of Medicine, Ulster University, Derry BT47 6SB, UK"},{"name":"Department of Neurology, Altnagelvin Hospital, Derry BT47 6SB, UK"},{"name":"Department of Neurology, Royal Victoria Hospital, Belfast BT12 6BA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Neurology, Royal Victoria Hospital, Belfast BT12 6BA, UK"},{"name":"Faculty of Medicine, Health & Life Sciences, Queen\u2019s University, Belfast BT9 6AG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"Donaghy","sequence":"additional","affiliation":[{"name":"Department of Neurology, Altnagelvin Hospital, Derry BT47 6SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederique","family":"Rene","sequence":"additional","affiliation":[{"name":"INSERM U1118, Centre de Recherche en Biom\u00e9decine de Strasbourg, Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2239-9094","authenticated-orcid":false,"given":"William","family":"Duddy","sequence":"additional","affiliation":[{"name":"Personalised Medicine Centre, School of Medicine, Ulster University, Derry BT47 6SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-5426","authenticated-orcid":false,"given":"Stephanie","family":"Duguez","sequence":"additional","affiliation":[{"name":"Personalised Medicine Centre, School of Medicine, Ulster University, Derry BT47 6SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3109\/17482960802566824","article-title":"Prognostic factors in ALS: A critical review","volume":"10","author":"Logroscino","year":"2009","journal-title":"Amy-Otrophic Lateral Scler."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1111\/ene.15172","article-title":"Epidemiology and survival trends of motor neurone disease in Northern Ireland from 2015 to 2019","volume":"29","author":"McCluskey","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.ncl.2015.07.001","article-title":"Familial Amyotrophic Lateral Sclerosis","volume":"33","author":"Boylan","year":"2015","journal-title":"Neurol. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1136\/jnnp-2022-328931","article-title":"Systematic evaluation of genetic mutations in ALS: A population-based study","volume":"93","author":"Grassano","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3389\/fnins.2019.01310","article-title":"ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?","volume":"13","author":"Mejzini","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Le Gall, L., Anakor, E., Connolly, O., Vijayakumar, U.G., Duddy, W.J., and Duguez, S. (2020). Molecular and Cellular Mechanisms Affected in ALS. J. Pers. Med., 10.","DOI":"10.1186\/s13395-020-00238-1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature20413","article-title":"Decoding ALS: From genes to mechanism","volume":"539","author":"Taylor","year":"2016","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11060-013-1084-8","article-title":"Biogenesis of extracellular vesicles (EV): Exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies","volume":"113","author":"Akers","year":"2013","journal-title":"J. Neuro-Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Doyle, L.M., and Wang, M.Z. (2019). Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, 8.","DOI":"10.3390\/cells8070727"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13578-019-0282-2","article-title":"Exosomes: Biogenesis, biologic function and clinical potential","volume":"9","author":"Zhang","year":"2019","journal-title":"Cell Biosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"R125","DOI":"10.1093\/hmg\/dds317","article-title":"Exosomes and microvesicles: Extracellular vesicles for genetic information transfer and gene therapy","volume":"21","author":"Lee","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"113","DOI":"10.4196\/kjpp.2018.22.2.113","article-title":"The potential theragnostic (diagnostic+therapeutic) application of exosomes in diverse biomedical fields","volume":"22","author":"Kim","year":"2018","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Anakor, E., Le Gall, L., Dumonceaux, J., Duddy, W.J., and Duguez, S. (2021). Exosomes in Ageing and Motor Neurone Disease: Biogenesis, Uptake Mechanisms, Modifications in Disease and Uses in the Development of Biomarkers and Therapeutics. Cells, 10.","DOI":"10.3390\/cells10112930"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s41392-020-00261-0","article-title":"Exosomes: Key players in cancer and potential therapeutic strategy","volume":"5","author":"Dai","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"767488","DOI":"10.3389\/fcvm.2021.767488","article-title":"Exosomes in Cardiovascular Diseases: Pathological Potential of Nano-Messenger","volume":"8","author":"Jadli","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9269","DOI":"10.1523\/JNEUROSCI.0147-18.2019","article-title":"Extracellular Vesicles and Neurodegenerative Diseases","volume":"39","author":"Hill","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrd3978","article-title":"Extracellular vesicles: Biology and emerging therapeutic opportunities","volume":"12","author":"Breakefield","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12964-021-00730-1","article-title":"The exosome journey: From biogenesis to uptake and intracellular signalling","volume":"19","author":"Gurung","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"114954","DOI":"10.1016\/j.bcp.2022.114954","article-title":"Biogenesis and function of extracellular vesicles in pathophysiological processes of skeletal muscle atrophy","volume":"198","author":"Wang","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"442","DOI":"10.3389\/fimmu.2014.00442","article-title":"Tetraspanins in extracellular vesicle formation and function","volume":"5","author":"Andreu","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/nature08849","article-title":"Molecular mechanism of multivesicular body biogenesis by ESCRT complexes","volume":"464","author":"Wollert","year":"2010","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1134\/S0006297920020054","article-title":"Lipid Rafts in Exosome Biogenesis","volume":"85","author":"Skryabin","year":"2020","journal-title":"Biochem. Mosc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1194\/jlr.R083915","article-title":"Role of sphingolipids in the biogenesis and biological activity of extracellular vesicles","volume":"59","author":"Verderio","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/tra.12803","article-title":"The role of lipids in exosome biology and intercellular communication: Function, analytics and applications","volume":"22","year":"2021","journal-title":"Traffic"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1038\/ncomms3712","article-title":"Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes","volume":"4","author":"Kajimoto","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"jcs259324","DOI":"10.1242\/jcs.259324","article-title":"Neutral sphingomyelinase 2 controls exosome secretion by counteracting V-ATPase-mediated endosome acidification","volume":"135","author":"Choezom","year":"2022","journal-title":"J. Cell Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/aps.2017.178","article-title":"Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools","volume":"39","author":"Li","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.plipres.2017.03.001","article-title":"Lipids in exosomes: Current knowledge and the way forward","volume":"66","author":"Skotland","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"O\u2019Neill, C.P., Gilligan, K.E., and Dwyer, R.M. (2019). Role of Extracellular Vesicles (EVs) in Cell Stress Response and Resistance to Cancer Therapy. Cancers, 11.","DOI":"10.3390\/cancers11020136"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"946422","DOI":"10.3389\/fimmu.2022.946422","article-title":"Translating extracellular vesicle packaging into therapeutic applications","volume":"13","author":"Ozkocak","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/jb\/mvaa109","article-title":"Senescence-associated extracellular vesicle release plays a role in senescence-associated secretory phenotype (SASP) in age-associated diseases","volume":"169","author":"Tanaka","year":"2020","journal-title":"J. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/prca.201400114","article-title":"Exosomes in bodily fluids are a highly stable resource of disease biomarkers","volume":"9","author":"Boukouris","year":"2015","journal-title":"Proteom.\u2013Clin. Appl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1080\/21541248.2016.1215283","article-title":"Biology and biogenesis of shed microvesicles","volume":"8","author":"Tricarico","year":"2016","journal-title":"Small GTPases"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R435","DOI":"10.1016\/j.cub.2018.01.059","article-title":"Exosomes and Ectosomes in Intercellular Communication","volume":"28","author":"Meldolesi","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"828","DOI":"10.3389\/fphys.2019.00828","article-title":"Contribution of Extracellular Vesicles in Rebuilding Injured Muscles","volume":"10","author":"Bittel","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3389\/fimmu.2019.00202","article-title":"Transcriptome of Extracellular Vesicles: State-of-the-Art","volume":"10","author":"Turchinovich","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Battistelli, M., and Falcieri, E. (2020). Apoptotic Bodies: Particular Extracellular Vesicles Involved in Intercellular Communication. Biology, 9.","DOI":"10.3390\/biology9010021"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"573511","DOI":"10.3389\/fcell.2020.573511","article-title":"Extracellular Vesicles Derived From Apoptotic Cells: An Essential Link Between Death and Regeneration","volume":"8","author":"Li","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24641","DOI":"10.3402\/jev.v3.24641","article-title":"Routes and mechanisms of extracellular vesicle uptake","volume":"3","author":"Mulcahy","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Prada, I., and Meldolesi, J. (2016). Binding and Fusion of Extracellular Vesicles to the Plasma Membrane of Their Cell Targets. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17081296"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kwok, Z.H., Wang, C., and Jin, Y. (2021). Extracellular Vesicle Transportation and Uptake by Recipient Cells: A Critical Process to Regulate Human Diseases. Processes, 9.","DOI":"10.3390\/pr9020273"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"114","DOI":"10.32607\/actanaturae.11478","article-title":"Targeting Extracellular Ves-icles to Dendritic Cells and Macrophages","volume":"13","author":"Ovchinnikova","year":"2021","journal-title":"Acta Nat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12951-018-0437-z","article-title":"Exosome origin determines cell targeting and the transfer of therapeutic nanoparticles towards target cells","volume":"17","author":"Mendoza","year":"2019","journal-title":"J. Nanobiotechnology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"31053","DOI":"10.3402\/jev.v5.31053","article-title":"Display of GPI-anchored anti-EGFR nano-bodies on extracellular vesicles promotes tumour cell targeting","volume":"5","author":"Kooijmans","year":"2016","journal-title":"J. Extracell. Vesicles"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Banks, W.A., Sharma, P., Bullock, K.M., Hansen, K.M., Ludwig, N., and Whiteside, T.L. (2020). Transport of Extracellular Vesicles across the Blood-Brain Barrier: Brain Pharmacokinetics and Effects of Inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124407"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"526","DOI":"10.3389\/fncel.2018.00526","article-title":"Extracellular Vesicles Secreted by As-troglial Cells Transport Apolipoprotein D to Neurons and Mediate Neuronal Survival Upon Oxidative Stress","volume":"12","author":"Lillo","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.neuron.2013.01.013","article-title":"Regulation of Postsynaptic Retrograde Signaling by Presynaptic Exosome Release","volume":"77","author":"Korkut","year":"2013","journal-title":"Neuron"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/cr.2017.62","article-title":"Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity","volume":"27","author":"Xu","year":"2017","journal-title":"Cell Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102124","DOI":"10.1016\/j.pneurobio.2021.102124","article-title":"The role of Extracellular Vesicles during CNS development","volume":"205","author":"Gomes","year":"2021","journal-title":"Prog. Neurobiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"623039","DOI":"10.3389\/fcell.2020.623039","article-title":"Extracellular Vesicles in Neuroinflammation","volume":"8","author":"Marostica","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nrneurol.2016.68","article-title":"Extracellular vesicles in neurodegenerative disease\u2014Pathogenesis to biomarkers","volume":"12","author":"Thompson","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1136\/jnnp-2020-325014","article-title":"Value of systematic genetic screening of patients with amyotrophic lateral sclerosis","volume":"92","author":"Shepheard","year":"2021","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.brainres.2018.02.035","article-title":"The epidemiology and genetics of Amyotrophic lateral sclerosis in China","volume":"1693","author":"Liu","year":"2018","journal-title":"Brain Res."},{"key":"ref_56","first-page":"1","article-title":"Genetics of amyotrophic lateral sclerosis: Seeking therapeutic targets in the era of gene therapy","volume":"2022","author":"Suzuki","year":"2022","journal-title":"J. Hum. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"227-e1","DOI":"10.1016\/j.neurobiolaging.2021.01.007","article-title":"Genetic epidemiology of familial ALS in Brazil","volume":"102","author":"Leoni","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"105144","DOI":"10.1016\/j.nbd.2020.105144","article-title":"Lessons learned from CHMP2B, implications for frontotemporal dementia and amyotrophic lateral sclerosis","volume":"147","author":"Ugbode","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"661447","DOI":"10.3389\/fncel.2021.661447","article-title":"C9ORF72: What It Is, What It Does, and Why It Matters","volume":"15","author":"Smeyers","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ajhg.2008.12.010","article-title":"Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS","volume":"84","author":"Chow","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Miceli, M., Exertier, C., Cavagli\u00e0, M., Gugole, E., Boccardo, M., Casaluci, R.R., Ceccarelli, N., De Maio, A., Vallone, B., and Deriu, M.A. (2022). ALS2-Related Motor Neuron Diseases: From Symptoms to Molecules. Biology, 11.","DOI":"10.3390\/biology11010077"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/s41419-021-03710-y","article-title":"Pathomechanisms of ALS8: Altered autophagy and defective RNA binding protein (RBP) homeostasis due to the VAPB P56S mutation","volume":"12","author":"Tripathi","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1080\/15548627.2019.1580103","article-title":"VAMP associated proteins are required for autophagic and lysosomal degradation by promoting a PtdIns4P-mediated endosomal pathway","volume":"15","author":"Mao","year":"2019","journal-title":"Autophagy"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.nbd.2017.02.007","article-title":"Loss of spatacsin function alters lysosomal lipid clearance leading to upper and lower motor neuron degeneration","volume":"102","author":"Branchu","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.1073\/pnas.1523926113","article-title":"Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria","volume":"113","author":"Richter","year":"2016","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_66","first-page":"1170","article-title":"Extracellular vesicles degradation pathway based autophagy lysosome pathway","volume":"11","author":"Zheng","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.2147\/JIR.S362865","article-title":"The Emerging Role of the Interaction of Extracellular Vesicle and Au-tophagy-Novel Insights into Neurological Disorders","volume":"15","author":"Wei","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/jnc.15255","article-title":"Cellular and physiological functions of C9ORF72 and implications for ALS\/FTD","volume":"157","author":"Pang","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"105653","DOI":"10.1016\/j.nbd.2022.105653","article-title":"The converging roles of sequestosome-1\/p62 in the molecular pathways of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)","volume":"166","author":"Davidson","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2017.04.005","article-title":"Optineurin in amyotrophic lateral sclerosis: Multifunctional adaptor protein at the crossroads of different neuroprotective mechanisms","volume":"154","author":"Markovinovic","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1093\/hmg\/ddu575","article-title":"Evidence of a link between ubiquilin 2 and optineurin in amyotrophic lateral sclerosis","volume":"24","author":"Osaka","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"841394","DOI":"10.3389\/fneur.2022.841394","article-title":"The Role of VCP Mutations in the Spectrum of Am-yotrophic Lateral Sclerosis-Frontotemporal Dementia","volume":"13","author":"Scarian","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Ferrari, V., Cristofani, R., Tedesco, B., Crippa, V., Chierichetti, M., Casarotto, E., Cozzi, M., Mina, F., Piccolella, M., and Galbiati, M. (2022). Valosin Containing Protein (VCP): A Multistep Regulator of Autophagy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23041939"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13041-017-0287-x","article-title":"TBK1: A new player in ALS linking autophagy and neuroinflammation","volume":"10","author":"Oakes","year":"2017","journal-title":"Mol. Brain"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/ana.21147","article-title":"Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations","volume":"61","author":"Mackenzie","year":"2007","journal-title":"Ann. Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e106389","DOI":"10.15252\/embj.2020106389","article-title":"Proteostatic imbalance and protein spreading in amyotrophic lateral sclerosis","volume":"40","author":"Cicardi","year":"2021","journal-title":"EMBO J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fnmol.2019.00262","article-title":"Prion-Like Propagation of Protein Misfolding and Aggregation in Amyo-trophic Lateral Sclerosis","volume":"12","author":"McAlary","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1136\/jnnp-2011-301826","article-title":"Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation?","volume":"83","author":"Kanouchi","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"899944","DOI":"10.3389\/fnagi.2022.899944","article-title":"The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer\u2019s Disease","volume":"14","author":"Weng","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-1-0716-1495-2_4","article-title":"Analysis of \u03b1-Synuclein in Exosomes","volume":"2322","author":"Tsunemi","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0169-328X(02)00583-1","article-title":"The Cu,Zn superoxide dismutase in neuroblastoma SK-N-BE cells is exported by a microvesicles dependent pathway","volume":"110","author":"Mondola","year":"2003","journal-title":"Mol. Brain Res."},{"key":"ref_83","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_84","doi-asserted-by":"crossref","first-page":"15699","DOI":"10.1074\/jbc.M112.425066","article-title":"Mutant copper-zinc superoxide dismutase (SOD1) induces protein secretion pathway alterations and exosome release in astrocytes: Implications for disease spreading and motor neuron pathology in amyotrophic lateral sclerosis","volume":"288","author":"Basso","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.celrep.2013.06.007","article-title":"Prion-like Properties of Pathological TDP-43 Aggregates from Diseased Brains","volume":"4","author":"Nonaka","year":"2013","journal-title":"Cell Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7105","DOI":"10.1074\/jbc.M112.410944","article-title":"Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate transporter GLT1","volume":"288","author":"Morel","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_87","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_88","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_89","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 BBA-Mol. Basis Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.celrep.2016.09.032","article-title":"Cell-to-Cell Transmission of Dipeptide Repeat Proteins Linked to C9orf72 -ALS\/FTD","volume":"17","author":"Westergard","year":"2016","journal-title":"Cell Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3389\/fnins.2017.00273","article-title":"Exosomes from NSC-34 Cells Transfected with hSOD1-G93A Are Enriched in miR-124 and Drive Alterations in Microglia Phenotype","volume":"11","author":"Pinto","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1074\/jbc.RA118.004825","article-title":"CNS-derived extracellular vesicles from superoxide dismutase 1 (SOD1)G93A ALS mice originate from astrocytes and neurons and carry misfolded SOD1","volume":"294","author":"Silverman","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.ebiom.2018.11.067","article-title":"Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS","volume":"40","author":"Varcianna","year":"2019","journal-title":"Ebiomedicine"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1002\/jcsm.12945","article-title":"Muscle cells of sporadic amyotrophic lateral sclerosis patients secrete neurotoxic vesicles","volume":"13","author":"Duddy","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_95","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_96","doi-asserted-by":"crossref","first-page":"3548","DOI":"10.1073\/pnas.1017275108","article-title":"Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells","volume":"108","author":"Bertolotti","year":"2011","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1016\/j.bbadis.2018.10.013","article-title":"Microglial overexpression of fALS-linked mutant SOD1 induces SOD1 processing impairment, activation and neurotoxicity and is counteracted by the autophagy inducer trehalose","volume":"1864","author":"Massenzio","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_98","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_99","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_100","doi-asserted-by":"crossref","first-page":"637548","DOI":"10.3389\/fncel.2021.637548","article-title":"Emerging Perspectives on Dipeptide Repeat Proteins in C9ORF72 ALS\/FTD","volume":"15","author":"Schmitz","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41580-020-0251-y","article-title":"RNA delivery by extracellular vesicles in mammalian cells and its applications","volume":"21","author":"Breyne","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1373\/clinchem.2010.147405","article-title":"The MicroRNA Spectrum in 12 Body Fluids","volume":"56","author":"Weber","year":"2010","journal-title":"Clin. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Jovi\u010di\u0107, A., and Gitler, A.D. (2017). Distinct repertoires of microRNAs present in mouse astrocytes compared to astrocyte-secreted exosomes. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171418"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-11534-w","article-title":"Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS","volume":"10","author":"Men","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1002\/2211-5463.13059","article-title":"Quantitative comparison of the mRNA content of human iPSC-derived motor neurons and their extracellular vesicles","volume":"11","author":"Otake","year":"2021","journal-title":"FEBS Open Bio"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3389\/fncel.2019.00109","article-title":"Phenotypic Effects of Wild-Type and Mutant SOD1 Expression in N9 Murine Microglia at Steady State, Inflammatory and Immunomodulatory Conditions","volume":"13","author":"Vaz","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/icb.2016.89","article-title":"Impaired activation of ALS monocytes by exo-somes","volume":"95","author":"Zondler","year":"2017","journal-title":"Immunol. Cell Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12987-022-00359-3","article-title":"Extracellular vesicles through the blood\u2013brain barrier: A review","volume":"19","author":"Polakovicova","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"110651","DOI":"10.1016\/j.celrep.2022.110651","article-title":"Uptake, functionality, and re-release of extracellular vesi-cle-encapsulated cargo","volume":"39","author":"Ughetto","year":"2022","journal-title":"Cell Rep."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Vassileff, N., Vella, L.J., Rajapaksha, H., Shambrook, M., Kenari, A.N., McLean, C., Hill, A.F., and Cheng, L. (2020). Revealing the Proteome of Motor Cortex Derived Extracellular Vesicles Isolated from Amyotrophic Lateral Sclerosis Human Postmortem Tissues. Cells, 9.","DOI":"10.3390\/cells9071709"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"574","DOI":"10.3389\/fnins.2019.00574","article-title":"Increased Interleukin-6 Levels in the Astrocyte-Derived Exosomes of Sporadic Amyotrophic Lateral Sclerosis Patients","volume":"13","author":"Chen","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"134176","DOI":"10.1016\/j.neulet.2019.03.048","article-title":"MicroRNA expression profiles of neuron-derived ex-tracellular vesicles in plasma from patients with amyotrophic lateral sclerosis","volume":"708","author":"Katsu","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Sproviero, D., Gagliardi, S., Zucca, S., Arigoni, M., Giannini, M., Garofalo, M., Olivero, M., Dell\u2019Orco, M., Pansarasa, O., and Bernuzzi, S. (2021). Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052737"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.brainres.2018.12.016","article-title":"Identification of a circulating miRNA signature in extracellular vesicles collected from amyotrophic lateral sclerosis patients","volume":"1708","author":"Saucier","year":"2018","journal-title":"Brain Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"200116","DOI":"10.1098\/rsob.200116","article-title":"An miRNA fingerprint using neural-enriched extracellular vesicles from blood plasma: To-wards a biomarker for amyotrophic lateral sclerosis\/motor neuron disease","volume":"10","author":"Banack","year":"2020","journal-title":"Open Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"120396","DOI":"10.1016\/j.jns.2022.120396","article-title":"miRNA extracted from extracellular vesicles is a robust biomarker of amyotrophic lateral sclerosis","volume":"442","author":"Banack","year":"2022","journal-title":"J. Neurol. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s12031-014-0471-8","article-title":"MicroRNAs as potential circulating biomarkers for amyotrophic lateral scle-rosis","volume":"56","author":"Cloutier","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"186","DOI":"10.3389\/fneur.2019.00186","article-title":"An Overview of MicroRNAs as Biomarkers of ALS","volume":"10","author":"Joilin","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Ricci, C., Marzocchi, C., and Battistini, S. (2018). MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis. Cells, 7.","DOI":"10.3390\/cells7110219"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Ravnik-Glava\u010d, M., and Glava\u010d, D. (2020). Circulating RNAs as Potential Biomarkers in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051714"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13395-014-0023-5","article-title":"The miR-206\/133b cluster is dispensable for development, survival and regeneration of skeletal muscle","volume":"4","author":"Boettger","year":"2014","journal-title":"Skelet. Muscle"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1007\/s12199-014-0405-7","article-title":"Three novel serum biomarkers, miR-1, miR-133a, and miR-206 for Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, and Becker muscular dystrophy","volume":"19","author":"Matsuzaka","year":"2014","journal-title":"Environ. Health Prev. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1096\/fj.08-128579","article-title":"Common micro-RNA signature in skeletal muscle damage and regeneration induced by Duchenne muscular dystrophy and acute ischemia","volume":"23","author":"Greco","year":"2009","journal-title":"FASEB J."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Malacarne, C., Galbiati, M., Giagnorio, E., Cavalcante, P., Salerno, F., Andreetta, F., Cagnoli, C., Taiana, M., Nizzardo, M., and Corti, S. (2021). Dysregulation of Muscle-Specific MicroRNAs as Common Pathogenic Feature Associated with Muscle Atrophy in ALS, SMA and SBMA: Evidence from Animal Models and Human Patients. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115673"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1038\/s41598-022-05067-4","article-title":"Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation","volume":"12","author":"Daneshafrooz","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Otake, K., Kamiguchi, H., and Hirozane, Y. (2019). Identification of biomarkers for amyotrophic lateral sclerosis by comprehensive analysis of exosomal mRNAs in human cerebrospinal fluid. BMC Med. Genom., 12.","DOI":"10.1186\/s12920-019-0473-z"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"785741","DOI":"10.3389\/fnagi.2022.785741","article-title":"Extracellular Vesicles Derived From Plasma of Patients With Neurodegenerative Disease Have Common Transcriptomic Profiling","volume":"14","author":"Sproviero","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1136\/jnnp-2021-327133","article-title":"Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis","volume":"93","author":"Thompson","year":"2021","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1212\/01.wnl.0000285080.70324.27","article-title":"Dyslipidemia is a protective factor in amyotrophic lateral sclerosis","volume":"70","author":"Dupuis","year":"2008","journal-title":"Neurology"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"McCluskey, G., Donaghy, C., Morrison, K.E., McConville, J., Duddy, W., and Duguez, S. (2022). The Role of Sphingomyelin and Ceramide in Motor Neuron Diseases. J. Pers. Med., 12.","DOI":"10.3390\/jpm12091418"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1093\/brain\/awac025","article-title":"Metabolomics identifies shared lipid pathways in independent amyotrophic lateral sclerosis cohorts","volume":"145","author":"Goutman","year":"2022","journal-title":"Brain"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.addr.2020.03.002","article-title":"An emerging focus on lipids in extracellular vesicles","volume":"159","author":"Skotland","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.chemphyslip.2018.08.003","article-title":"Sphingolipids and lipid rafts: Novel concepts and methods of analysis","volume":"216","author":"Bieberich","year":"2018","journal-title":"Chem. Phys. Lipids"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1002\/pmic.201200329","article-title":"Proteomics, transcriptomics and lipidomics of exosomes and ectosomes","volume":"13","author":"Choi","year":"2013","journal-title":"Proteomics"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"102249","DOI":"10.1016\/j.nano.2020.102249","article-title":"Raman spectroscopy reveals biochemical dif-ferences in plasma derived extracellular vesicles from sporadic Amyotrophic Lateral Sclerosis patients","volume":"29","author":"Morasso","year":"2020","journal-title":"Nanomedicine"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3109\/21678421.2014.905606","article-title":"Limited role of free TDP-43 as a diagnostic tool in neurodegenerative diseases","volume":"15","author":"Feneberg","year":"2014","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3389\/fnins.2018.00487","article-title":"Pathological Proteins Are Transported by Ex-tracellular Vesicles of Sporadic Amyotrophic Lateral Sclerosis Patients","volume":"12","author":"Sproviero","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3389\/fnins.2019.00344","article-title":"Leukocyte Derived Microvesicles as Disease Progression Biomarkers in Slow Progressing Amyotrophic Lateral Sclerosis Patients","volume":"13","author":"Sproviero","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"117070","DOI":"10.1016\/j.jns.2020.117070","article-title":"Exosomal TAR DNA-binding protein-43 and neurofilaments in plasma of amyotrophic lateral sclerosis patients: A longitudinal follow-up study","volume":"418","author":"Chen","year":"2020","journal-title":"J. Neurol. Sci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.neures.2019.10.010","article-title":"Proteomic analysis of exosome-enriched fractions derived from cerebrospinal fluid of amyotrophic lateral sclerosis patients","volume":"160","author":"Hayashi","year":"2019","journal-title":"Neurosci. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12014-020-09294-7","article-title":"CSF extracellular vesicle proteomics demonstrates altered protein homeostasis in amyotrophic lateral sclerosis","volume":"17","author":"Thompson","year":"2020","journal-title":"Clin. Proteom."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13024-021-00470-3","article-title":"Additional file 1 of Decoding distinctive features of plasma extracellular vesicles in amyotrophic lateral sclerosis","volume":"16","author":"Pasetto","year":"2021","journal-title":"Molecular neurodegeneration"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"13","DOI":"10.5582\/irdr.2017.01091","article-title":"Comparison of the extraction and determination of serum exosome and miRNA in serum and the detection of miR-27a-3p in serum exosome of ALS patients","volume":"7","author":"Xu","year":"2018","journal-title":"Intractable Rare Dis. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"113414","DOI":"10.1016\/j.expneurol.2020.113414","article-title":"Elevated exosomal secretion of miR-124-3p from spinal neurons positively associates with disease severity in ALS","volume":"333","author":"Yelick","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Pregnolato, F., Cova, L., Doretti, A., Bardelli, D., Silani, V., and Bossolasco, P. (2021). Exosome microRNAs in Amyotrophic Lateral Sclerosis: A Pilot Study. Biomolecules, 11.","DOI":"10.3390\/biom11081220"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Sidhom, K., Obi, P., and Saleem, A. (2020). A Review of Exosomal Isolation Methods: Is Size Exclusion Chromatography the Best Option?. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202007.0485.v2"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"789","DOI":"10.7150\/thno.18133","article-title":"Progress in Exosome Isolation Techniques","volume":"7","author":"Li","year":"2017","journal-title":"Theranostics"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4103\/bc.bc_9_21","article-title":"Extracellular vesicle-based therapy for amyotrophic lateral sclerosis","volume":"7","author":"Sadanandan","year":"2021","journal-title":"Brain Circ."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41565-021-00931-2","article-title":"Extracellular vesicles as a next-generation drug delivery platform","volume":"16","author":"Herrmann","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s00018-020-03619-3","article-title":"Extracellular vesicles and amyotrophic lateral sclerosis: From misfolded protein vehicles to promising clinical biomarkers","volume":"78","author":"Gagliardi","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.4103\/1673-5374.165305","article-title":"Exosomes in neurological disease, neuroprotection, repair and therapeutics: Problems and perspectives","volume":"10","author":"Kalani","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1002\/mds.25978","article-title":"Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice","volume":"29","author":"Cooper","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","author":"Seow","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3675627","DOI":"10.1155\/2019\/3675627","article-title":"Mesenchymal Stem Cells: A Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis?","volume":"2019","author":"Gugliandolo","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13024-017-0227-3","article-title":"Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis","volume":"12","author":"Ciervo","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Araldi, R.P., D\u2019Amelio, F., Vigerelli, H., De Melo, T.C., and Kerkis, I. (2020). Stem Cell-Derived Exosomes as Therapeutic Approach for Neurodegenerative Disorders: From Biology to Biotechnology. Cells, 9.","DOI":"10.3390\/cells9122663"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.bbrc.2016.09.069","article-title":"Adipose-derived stem cell exosomes alleviate pathology of amyotrophic lateral sclerosis in vitro","volume":"479","author":"Lee","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.yexcr.2015.12.009","article-title":"Exosome derived from murine adipose-derived stromal cells: Neuroprotective effect on in vitro model of amyotrophic lateral sclerosis","volume":"340","author":"Bonafede","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.3389\/fnins.2019.01070","article-title":"ASCs-Exosomes Recover Coupling Efficiency and Mitochondrial Membrane Potential in an in vitro Model of ALS","volume":"13","author":"Calabria","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Bonafede, R., Brandi, J., Manfredi, M., Scambi, I., Schiaffino, L., Merigo, F., Turano, E., Bonetti, B., Marengo, E., and Cecconi, D. (2019). The Anti-Apoptotic Effect of ASC-Exosomes in an In Vitro ALS Model and Their Proteomic Analysis. Cells, 8.","DOI":"10.3390\/cells8091087"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Bonafede, R., Turano, E., Scambi, I., Busato, A., Bontempi, P., Virla, F., Schiaffino, L., Marzola, P., Bonetti, B., and Mariotti, R. (2020). ASC-Exosomes Ameliorate the Disease Progression in SOD1(G93A) Murine Model Underlining Their Potential Therapeutic Use in Human ALS. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103651"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s12017-020-08607-1","article-title":"Cell-Free Extracellular Vesicles Derived from Human Bone Marrow Endothelial Progenitor Cells as Potential Therapeutics for Microvascular Endothelium Restoration in ALS","volume":"22","author":"Willing","year":"2020","journal-title":"NeuroMolecular Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1038\/s41598-021-81039-4","article-title":"Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation","volume":"11","author":"Giunti","year":"2021","journal-title":"Sci. Rep."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/1\/121\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:20Z","timestamp":1760147360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/1\/121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,31]]},"references-count":165,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["life13010121"],"URL":"https:\/\/doi.org\/10.3390\/life13010121","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,31]]}}}