{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:14:50Z","timestamp":1792030490969,"version":"4.4.0"},"reference-count":81,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8F1791"],"award-info":[{"award-number":["CMRPG8F1791"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8J1351"],"award-info":[{"award-number":["CMRPG8J1351"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Macrophages emerge in the milieu around innervated neurons after nerve injuries. Following nerve injury, autophagy is induced in macrophages and affects the regulation of inflammatory responses. It is closely linked to neuroinflammation, while the immunosuppressive drug tacrolimus (FK506) enhances nerve regeneration following nerve crush injury and nerve allotransplantation with additional neuroprotective and neurotrophic functions. The combined use of FK506 and adipose-derived stem cells (ADSCs) was employed in cell therapy for organ transplantation and vascularized composite allotransplantation. This study aimed to investigate the topical application of exosomes secreted by ADSCs following FK506 treatment (ADSC-F-exo) to the injured nerve in a mouse model of sciatic nerve crush injury. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile the potential exosomal proteins involved in autophagy. Immunohistochemical analysis revealed that nerve crush injuries significantly induced autophagy in the dorsal root ganglia and dorsal horn of the spinal segments. Locally applied ADSC-F-exo significantly reduced autophagy of macrophages in the spinal segments after nerve crush injury. Proteomic analysis showed that of the 22 abundant exosomal proteins detected in ADSC-F-exo, heat shock protein family A member 8 (HSPA8) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) are involved in exosome-mediated autophagy reduction.<\/jats:p>","DOI":"10.3390\/ijms22179628","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T21:47:38Z","timestamp":1630964858000},"page":"9628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Exosomes Secreted by Adipose-Derived Stem Cells Following FK506 Stimulation Reduce Autophagy of Macrophages in Spine after Nerve Crush Injury"],"prefix":"10.3390","volume":"22","author":[{"given":"Pao-Jen","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Shyuan","family":"Rau","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0984-6921","authenticated-orcid":false,"given":"Shao-Chun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien-Hung","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsu-Hsiang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Jung","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0945-2746","authenticated-orcid":false,"given":"Ching-Hua","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Center for Vascularized Composite Allotransplantation, Chang Gung Memorial Hospital, LinKou 33333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.neuron.2016.01.034","article-title":"A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program","volume":"89","author":"Chandran","year":"2016","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.pneurobio.2018.12.001","article-title":"Macrophage biology in the peripheral nervous system after injury","volume":"173","author":"Zigmond","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.autneu.2013.12.009","article-title":"Inflammation in dorsal root ganglia after peripheral nerve injury: Effects of the sympathetic innervation","volume":"182","author":"McLachlan","year":"2014","journal-title":"Auton. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.celrep.2018.03.071","article-title":"Sarm1\/Myd88-5 Regulates Neuronal Intrinsic Immune Response to Traumatic Axonal Injuries","volume":"23","author":"Wang","year":"2018","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16236","DOI":"10.1523\/JNEUROSCI.3319-12.2013","article-title":"A critical role for macrophages near axotomized neuronal cell bodies in stimulating nerve regeneration","volume":"33","author":"Niemi","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.cell.2015.07.021","article-title":"Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves","volume":"162","author":"Cattin","year":"2015","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/01.LAB.0000056993.28149.BF","article-title":"Macrophage response to peripheral nerve injury: The quantitative contribution of resident and hematogenous macrophages","volume":"83","author":"Mueller","year":"2003","journal-title":"Lab. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.4103\/1673-5374.143423","article-title":"Function of microglia and macrophages in secondary damage after spinal cord injury","volume":"9","author":"Zhou","year":"2014","journal-title":"Neural Regen Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1089\/ars.2015.6306","article-title":"Function and Mechanisms of Autophagy in Brain and Spinal Cord Trauma","volume":"23","author":"Lipinski","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1126\/science.290.5497.1717","article-title":"Autophagy as a regulated pathway of cellular degradation","volume":"290","author":"Klionsky","year":"2000","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pugsley, H.R. (2017). Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry. J. Vis. Exp., 125.","DOI":"10.3791\/55637"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2015.03.002","article-title":"Autophagy in axonal degeneration in glaucomatous optic neuropathy","volume":"47","author":"Munemasa","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6064","DOI":"10.1073\/pnas.0909794107","article-title":"Mechanisms of acute axonal degeneration in the optic nerve in vivo","volume":"107","author":"Koch","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.exer.2015.08.016","article-title":"The role of autophagy in axonal degeneration of the optic nerve","volume":"144","author":"Koch","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1002\/jnr.21738","article-title":"Activation of autophagy in retinal ganglion cells","volume":"86","author":"Kim","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/cdd.2011.88","article-title":"Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice","volume":"19","author":"Germain","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liu, W.J., Ye, L., Huang, W.F., Guo, L.J., Xu, Z.G., Wu, H.L., Yang, C., and Liu, H.F. (2016). p62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation. Cell Mol. Biol. Lett., 21.","DOI":"10.1186\/s11658-016-0031-z"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neuroscience.2019.10.046","article-title":"Hydrogen-rich Saline Alleviated the Hyperpathia and Microglia Activation via Autophagy Mediated Inflammasome Inactivation in Neuropathic Pain Rats","volume":"421","author":"Chen","year":"2019","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Plaza-Zabala, A., Sierra-Torre, V., and Sierra, A. (2017). Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030598"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ma, Z., Han, Q., Wang, X., Ai, Z., and Zheng, Y. (2016). Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148792"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/mus.26760","article-title":"Stem-cell-based therapies to enhance peripheral nerve regeneration","volume":"61","author":"Kubiak","year":"2020","journal-title":"Muscle Nerve"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.4103\/1673-5374.303009","article-title":"The interaction of stem cells and vascularity in peripheral nerve regeneration","volume":"16","author":"Saffari","year":"2021","journal-title":"Neural Regen Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1080\/14712598.2019.1576630","article-title":"Advances in stem cell treatment for sciatic nerve injury","volume":"19","author":"Nasiri","year":"2019","journal-title":"Expert Opin. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/5584_2020_547","article-title":"The Cellular and Molecular Patterns Involved in the Neural Differentiation of Adipose-Derived Stem Cells","volume":"1298","author":"Selaru","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.sxmr.2019.09.006","article-title":"Current Status and Prospects in the Treatment of Erectile Dysfunction by Adipose-Derived Stem Cells in the Diabetic Animal Model","volume":"8","author":"Yan","year":"2020","journal-title":"Sex. Med. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1089\/scd.2013.0396","article-title":"Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair","volume":"23","author":"Kingham","year":"2014","journal-title":"Stem Cells Dev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1089\/scd.2011.0403","article-title":"Adipose-derived stem cells produce factors enhancing peripheral nerve regeneration: Influence of age and anatomic site of origin","volume":"21","author":"Sowa","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/978-1-4939-2550-6_15","article-title":"A protocol for exosome isolation and characterization: Evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods","volume":"1295","author":"Greening","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lin, J., Li, J., Huang, B., Liu, J., Chen, X., Chen, X.M., Xu, Y.M., Huang, L.F., and Wang, X.Z. (2015). Exosomes: Novel biomarkers for clinical diagnosis. Sci. World J., 2015.","DOI":"10.1155\/2015\/657086"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1007\/s12035-018-1172-z","article-title":"Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury","volume":"56","author":"Bucan","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.jcyt.2015.01.005","article-title":"Murine adipose-derived mesenchymal stromal cell vesicles: In vitro clues for neuroprotective and neuroregenerative approaches","volume":"17","author":"Farinazzo","year":"2015","journal-title":"Cytotherapy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.yexcr.2018.08.021","article-title":"Exosomes derived from PEDF modified adipose-derived mesenchymal stem cells ameliorate cerebral ischemia-reperfusion injury by regulation of autophagy and apoptosis","volume":"371","author":"Huang","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.4049\/jimmunol.1390055","article-title":"Calcineurin inhibitors: 40 years later, can\u2019t live without","volume":"191","author":"Azzi","year":"2013","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1586\/1744666X.2016.1123093","article-title":"Tacrolimus for the prevention and treatment of rejection of solid organ transplants","volume":"12","author":"Scalea","year":"2016","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.jsxm.2018.07.009","article-title":"A Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Utility of Tacrolimus (FK506) for the Prevention of Erectile Dysfunction Following Bilateral Nerve-Sparing Radical Prostatectomy","volume":"15","author":"Mulhall","year":"2018","journal-title":"J. Sex. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1177\/1545968311431965","article-title":"Efficacy of short-term FK506 administration on accelerating nerve regeneration","volume":"26","author":"Yan","year":"2012","journal-title":"Neurorehabil. Neural Repair"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.jhsa.2020.03.018","article-title":"Systemic and Local FK506 (Tacrolimus) and its Application in Peripheral Nerve Surgery","volume":"45","author":"Zuo","year":"2020","journal-title":"J. Hand Surg. Am."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jss.2018.01.016","article-title":"Adipose-derived mesenchymal stem cells attenuate rejection in a rat lung transplantation model","volume":"227","author":"Watanabe","year":"2018","journal-title":"J. Surg. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1111\/ajt.15726","article-title":"Adipose-derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long-term graft tolerance in vascularized composite allotransplantation","volume":"20","author":"Schweizer","year":"2020","journal-title":"Am. J. Transplant."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1097\/TA.0000000000001489","article-title":"Differential inflammatory networks distinguish responses to bone marrow-derived versus adipose-derived mesenchymal stem cell therapies in vascularized composite allotransplantation","volume":"83","author":"Zamora","year":"2017","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rau, C.-S., Kuo, P.-J., Wu, S.-C., Huang, L.-H., Lu, T.-H., Wu, Y.-C., Wu, C.-J., Lin, C.-W., Tsai, C.-W., and Hsieh, C.-H. (2021). Enhanced Nerve Regeneration by Exosomes Secreted by Adi-pose-Derived Stem Cells with or Without FK506 Stimulation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168545"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"D380","DOI":"10.1093\/nar\/gkx1013","article-title":"TRRUST v2: An expanded reference database of human and mouse transcriptional regulatory interactions","volume":"46","author":"Han","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.exer.2015.06.016","article-title":"Hypoxia inducible factor 1\u03b1 contributes to regulation of autophagy in retinal detachment","volume":"137","author":"Shelby","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1089\/neu.2018.6364","article-title":"Stabilization of Hypoxia Inducible Factor-1\u03b1 by Dimethyloxalylglycine Promotes Recovery from Acute Spinal Cord Injury by Inhibiting Neural Apoptosis and Enhancing Axon Regeneration","volume":"36","author":"Li","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ceb.2009.11.015","article-title":"Hypoxia-induced autophagy: Cell death or cell survival?","volume":"22","author":"Mazure","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.neuron.2015.09.050","article-title":"Activating Injury-Responsive Genes with Hypoxia Enhances Axon Regeneration through Neuronal HIF-1\u03b1","volume":"88","author":"Cho","year":"2015","journal-title":"Neuron"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.neuropharm.2016.03.009","article-title":"Treatment with an activator of hypoxia-inducible factor 1, DMOG provides neuroprotection after traumatic brain injury","volume":"107","author":"Sen","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jns.2012.08.036","article-title":"Neuronal damage and functional deficits are ameliorated by inhibition of aquaporin and HIF1\u03b1 after traumatic brain injury (TBI)","volume":"323","author":"Shenaq","year":"2012","journal-title":"J. Neurol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ijdevneu.2019.06.001","article-title":"Neuroglobin protects offspring rats from neuronal damage induced by sevoflurane exposure to pregnant rats by inhibiting endogenous apoptosis","volume":"76","author":"Zhang","year":"2019","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Romeo-Guitart, D., Leiva-Rodriguez, T., For\u00e9s, J., and Casas, C. (2019). Improved Motor Nerve Regeneration by SIRT1\/Hif1a-Mediated Autophagy. Cells, 8.","DOI":"10.3390\/cells8111354"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.pharmthera.2012.08.014","article-title":"Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential","volume":"136","author":"Liu","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/jnr.21124","article-title":"Translocation of constitutively expressed heat shock protein Hsc70 to synapse-enriched areas of the cerebral cortex after hyperthermic stress","volume":"85","author":"Chen","year":"2007","journal-title":"J. Neurosci. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1046\/j.1460-9568.2002.01998.x","article-title":"Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70","volume":"15","author":"Rubio","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s10571-020-00897-0","article-title":"Autophagic Pathways to Clear the Tau Aggregates in Alzheimer\u2019s Disease","volume":"41","author":"Gorantla","year":"2021","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1379\/1466-1268(2004)009<0088:AOHIVI>2.0.CO;2","article-title":"Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration","volume":"9","author":"Tidwell","year":"2004","journal-title":"Cell Stress Chaperones"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/dneu.20550","article-title":"Exogenous Hsc70, but not thermal preconditioning, confers protection to motoneurons subjected to oxidative stress","volume":"68","author":"Robinson","year":"2008","journal-title":"Dev. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.sbi.2005.05.004","article-title":"Elongation factors on the ribosome","volume":"15","author":"Nilsson","year":"2005","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_59","first-page":"2665","article-title":"Association of translation factor eEF1A with defective ribosomal products generates a signal for aggresome formation","volume":"125","author":"Meriin","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Park, J., Park, Y., Ryu, I., Choi, M.H., Lee, H.J., Oh, N., Kim, K., Kim, K.M., Choe, J., and Lee, C. (2017). Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex. Nat. Commun., 8.","DOI":"10.1038\/ncomms15730"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3389\/fnins.2020.00303","article-title":"Downregulation of eEF1A\/EFT3-4 Enhances Dopaminergic Neurodegeneration After 6-OHDA Exposure in C. elegans Model","volume":"14","author":"Chalorak","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_62","first-page":"1079","article-title":"Crosstalk between translation and the aggresome-autophagy pathway","volume":"14","author":"Park","year":"2018","journal-title":"Autophagy"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1158\/0008-5472.CAN-08-4042","article-title":"Cathepsin D and eukaryotic translation elongation factor 1 as promising markers of cellular senescence","volume":"69","author":"Byun","year":"2009","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/cdd.2008.136","article-title":"Novel cell death by downregulation of eEF1A1 expression in tetraploids","volume":"16","author":"Kobayashi","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Salimi, L., Akbari, A., Jabbari, N., Mojarad, B., Vahhabi, A., Szafert, S., Kalashani, S.A., Soraya, H., Nawaz, M., and Rezaie, J. (2020). Synergies in exosomes and autophagy pathways for cellular homeostasis and metastasis of tumor cells. Cell Biosci., 10.","DOI":"10.1186\/s13578-020-00426-y"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.bulcan.2020.11.004","article-title":"An overview of autophagy: Mechanism, regulation and research progress","volume":"108","author":"Cao","year":"2021","journal-title":"Bull. Cancer"},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1080\/15548627.2018.1535292","article-title":"Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration","volume":"15","author":"Rusmini","year":"2019","journal-title":"Autophagy"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Tang, X., and Sun, C. (2020). The roles of MicroRNAs in neural regenerative medicine. Exp. Neurol., 332.","DOI":"10.1016\/j.expneurol.2020.113394"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"He, L., Zhu, C., Jia, J., Hao, X.Y., Yu, X.Y., Liu, X.Y., and Shu, M.G. (2020). ADSC-Exos containing MALAT1 promotes wound healing by targeting miR-124 through activating Wnt\/\u03b2-catenin pathway. Biosci. Rep., 40.","DOI":"10.1042\/BSR20192549"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.exer.2016.05.016","article-title":"Resident corneal c-fms(+) macrophages and dendritic cells mediate early cellular infiltration in adenovirus keratitis","volume":"147","author":"Ramke","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Th\u00e9ry, C., Witwer, K.W., Aikawa, E., Alcaraz, M.J., Anderson, J.D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., and Atkin-Smith, G.K. (2018). 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. J. Extracell. Vesicles, 7.","DOI":"10.1080\/20013078.2018.1535750"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1189\/jlb.0903442","article-title":"Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene","volume":"75","author":"Burnett","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"80741","DOI":"10.18632\/oncotarget.20206","article-title":"Knockout of toll-like receptor impairs nerve regeneration after a crush injury","volume":"8","author":"Hsieh","year":"2017","journal-title":"Oncotarget"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Wu, S.C., Rau, C.S., Lu, T.H., Wu, C.J., Wu, Y.C., Tzeng, S.L., Chen, Y.C., and Hsieh, C.H. (2013). Knockout of TLR4 and TLR2 impair the nerve regeneration by delayed demyelination but not remyelination. J. Biomed. Sci., 20.","DOI":"10.1186\/1423-0127-20-62"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Zhou, B., Pache, L., Chang, M., Khodabakhshi, A.H., Tanaseichuk, O., Benner, C., and Chanda, S.K. (2019). Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun., 10.","DOI":"10.1038\/s41467-019-09234-6"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"D535","DOI":"10.1093\/nar\/gkj109","article-title":"BioGRID: A general repository for interaction datasets","volume":"34","author":"Stark","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/nmeth.4077","article-title":"OmniPath: Guidelines and gateway for literature-curated signaling pathway resources","volume":"13","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nmeth.4083","article-title":"A scored human protein-protein interaction network to catalyze genomic interpretation","volume":"14","author":"Li","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Bader, G.D., and Hogue, C.W. (2003). An automated method for finding molecular complexes in large protein interaction networks. 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