{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:54:43Z","timestamp":1780606483461,"version":"3.54.1"},"reference-count":82,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011692","name":"General Insurance Association of Japan","doi-asserted-by":"publisher","award":["JP21H03558"],"award-info":[{"award-number":["JP21H03558"]}],"id":[{"id":"10.13039\/501100011692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011692","name":"General Insurance Association of Japan","doi-asserted-by":"publisher","award":["JP21gm6210004"],"award-info":[{"award-number":["JP21gm6210004"]}],"id":[{"id":"10.13039\/501100011692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21H03558"],"award-info":[{"award-number":["JP21H03558"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21gm6210004"],"award-info":[{"award-number":["JP21gm6210004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kobayashi Foundation","award":["JP21H03558"],"award-info":[{"award-number":["JP21H03558"]}]},{"name":"Kobayashi Foundation","award":["JP21gm6210004"],"award-info":[{"award-number":["JP21gm6210004"]}]},{"name":"SEI Group CSR Foundation","award":["JP21H03558"],"award-info":[{"award-number":["JP21H03558"]}]},{"name":"SEI Group CSR Foundation","award":["JP21gm6210004"],"award-info":[{"award-number":["JP21gm6210004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite recent advancements in therapeutic options for disorders of the central nervous system (CNS), the lack of an efficient drug-delivery system (DDS) hampers their clinical application. We hypothesized that liposomes could be optimized for retrograde transport in axons as a DDS from peripheral tissues to the spinal cord and dorsal root ganglia (DRGs). Three types of liposomes consisting of DSPC, DSPC\/POPC, or POPC in combination with cholesterol (Chol) and polyethylene glycol (PEG) lipid were administered to sciatic nerves or the tibialis anterior muscle of mature rats. Liposomes in cell bodies were detected with infrared fluorescence of DiD conjugated to liposomes. Three days later, all nerve-administered liposomes were retrogradely transported to the spinal cord and DRGs, whereas only muscle-administered liposomes consisting of DSPC reached the spinal cord and DRGs. Modification with Cholera toxin B subunit improved the transport efficiency of liposomes to the spinal cord and DRGs from 4.5% to 17.3% and from 3.9% to 14.3% via nerve administration, and from 2.6% to 4.8% and from 2.3% to 4.1% via muscle administration, respectively. Modification with octa-arginine (R8) improved the transport efficiency via nerve administration but abolished the transport capability via muscle administration. These findings provide the initial data for the development of a novel DDS targeting the spinal cord and DRGs via peripheral administration.<\/jats:p>","DOI":"10.3390\/ijms23126661","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T22:17:01Z","timestamp":1655331421000},"page":"6661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification"],"prefix":"10.3390","volume":"23","author":[{"given":"Takafumi","family":"Fukui","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironao","family":"Tateno","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-5102","authenticated-orcid":false,"given":"Yuma","family":"Yamada","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0913-7815","authenticated-orcid":false,"given":"Yusuke","family":"Sato","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-4046","authenticated-orcid":false,"given":"Norimasa","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyoshi","family":"Harashima","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Kadoya","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/156652307781369083","article-title":"Gene therapy for peripheral nervous system diseases","volume":"7","author":"Federici","year":"2007","journal-title":"Curr. Gene Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1136\/practneurol-2011-000155","article-title":"Spasticity: Pathophysiology, evaluation and management","volume":"12","author":"Kheder","year":"2012","journal-title":"Pract. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.pain.2014.05.004","article-title":"Prevention of NKCC1 phosphorylation avoids downregulation of KCC2 in central sensory pathways and reduces neuropathic pain after peripheral nerve injury","volume":"155","author":"Cobianchi","year":"2014","journal-title":"Pain"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nabizadeh, F., Balabandian, M., Sharafi, A.M., Ghaderi, A., Rostami, M.R., and Naser Moghadasi, A. (2021). Statins and risk of amyotrophic lateral sclerosis: A systematic review and meta-analysis. Acta Neurol. Belg.","DOI":"10.1007\/s13760-021-01753-8"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.3389\/fphys.2019.01258","article-title":"Low-Intensity Running and High-Intensity Swimming Exercises Differentially Improve Energy Metabolism in Mice with Mild Spinal Muscular Atrophy","volume":"10","author":"Houdebine","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.neuint.2019.04.003","article-title":"Role of the BDNF-TrkB pathway in KCC2 regulation and rehabilitation following neuronal injury: A mini review","volume":"128","author":"Uchiyama","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nrd.2015.21","article-title":"From blood-brain barrier to blood-brain interface: New opportunities for CNS drug delivery","volume":"15","author":"Banks","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1016\/j.ultrasmedbio.2019.05.022","article-title":"Ultrasound-Induced Blood-Spinal Cord Barrier Opening in Rabbits","volume":"45","author":"Montero","year":"2019","journal-title":"Ultrasound Med. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113244","DOI":"10.1016\/j.expneurol.2020.113244","article-title":"Characteristics of the nerve barrier and the blood dorsal root ganglion barrier in health and disease","volume":"327","author":"Reinhold","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.addr.2020.02.006","article-title":"Intrathecal drug delivery in the era of nanomedicine","volume":"165\u2013166","author":"Fowler","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1021\/mp300474m","article-title":"Physiology of the intrathecal bolus: The leptomeningeal route for macromolecule and particle delivery to CNS","volume":"10","author":"Papisov","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.2147\/IJN.S61288","article-title":"Current approaches to enhance CNS delivery of drugs across the brain barriers","volume":"9","author":"Lu","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104829","DOI":"10.1016\/j.micinf.2021.104829","article-title":"Retrograde Axonal Transport Property of Adeno-Associated Virus and Its Possible Application in Future","volume":"23","author":"Wang","year":"2021","journal-title":"Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1179069519889022","DOI":"10.1177\/1179069519889022","article-title":"Gene Transfer in Rodent Nervous Tissue following Hindlimb Intramuscular Delivery of Recombinant Adeno-Associated Virus Serotypes AAV2\/6, AAV2\/8, and AAV2\/9","volume":"14","author":"Jan","year":"2019","journal-title":"Neurosci. Insights"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6920","DOI":"10.1523\/JNEUROSCI.22-16-06920.2002","article-title":"Neuroprotective effects of glial cell line-derived neurotrophic factor mediated by an adeno-associated virus vector in a transgenic animal model of amyotrophic lateral sclerosis","volume":"22","author":"Wang","year":"2002","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.omtm.2019.11.006","article-title":"rAAV2-Retro Enables Extensive and High-Efficient Transduction of Lower Motor Neurons following Intramuscular Injection","volume":"17","author":"Chen","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/mt.2012.261","article-title":"Intramuscular scAAV9-SMN injection mediates widespread gene delivery to the spinal cord and decreases disease severity in SMA mice","volume":"21","author":"Besse","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/jnr.24109","article-title":"Motoneuron activity is required for enhancements in functional recovery after peripheral nerve injury in exercised female mice","volume":"98","author":"Jaiswal","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/hum.2007.093","article-title":"Neonatal intraperitoneal or intravenous injections of recombinant adeno-associated virus type 8 transduce dorsal root ganglia and lower motor neurons","volume":"19","author":"Foust","year":"2008","journal-title":"Hum. Gene Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/sj.mt.6300367","article-title":"Efficient Retrograde Neuronal Transduction Utilizing Self-complementary AAV1","volume":"16","author":"Kadoya","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1089\/hum.2009.131","article-title":"Efficient retrograde transport of adeno-associated virus type 8 to spinal cord and dorsal root ganglion after vector delivery in muscle","volume":"21","author":"Zheng","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-1-4939-9139-6_13","article-title":"Peripheral AAV Injection for Retrograde Transduction of Dorsal Root and Trigeminal Ganglia","volume":"1950","author":"Bloom","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8507","DOI":"10.2147\/IJN.S183117","article-title":"Liposome delivery systems for the treatment of Alzheimer\u2019s disease","volume":"13","author":"Ross","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"119329","DOI":"10.1016\/j.biomaterials.2019.119329","article-title":"Innovative nanotechnologies for enhancing nucleic acids\/gene therapy: Controlling intracellular trafficking to targeted biodistribution","volume":"218","author":"Nakamura","year":"2019","journal-title":"Biomaterials"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1248\/bpb.b16-00624","article-title":"Liposomal Delivery Systems: Design Optimization and Current Applications","volume":"40","author":"Ishida","year":"2017","journal-title":"Biol. Pharm. Bull."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Raoufi, E., Bahramimeimandi, B., Salehi-Shadkami, M., Chaosri, P., and Mozafari, M.R. (2021). Methodical Design of Viral Vaccines Based on Avant-Garde Nanocarriers: A Multi-Domain Narrative Review. Biomedicines, 9.","DOI":"10.3390\/biomedicines9050520"},{"key":"ref_27","first-page":"417","article-title":"Antibodies for COVID-19\u2014Which, when and how long?","volume":"35","author":"Theoharides","year":"2021","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.2217\/nnm.16.9","article-title":"Recent advances in liposome surface modification for oral drug delivery","volume":"11","author":"Nguyen","year":"2016","journal-title":"Nanomed. Lond. Engl."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jneumeth.2016.09.003","article-title":"A novel approach for targeted delivery to motoneurons using cholera toxin-B modified protocells","volume":"273","author":"Durfee","year":"2016","journal-title":"J. Neurosci. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1039\/C5TB02079D","article-title":"Cellular Endocytosis and Trafficking of Cholera Toxin B-Modified Mesoporous Silica Nanoparticles","volume":"4","author":"Walker","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.1074\/jbc.M007540200","article-title":"Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery","volume":"276","author":"Futaki","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.nano.2018.01.002","article-title":"Uptake and intracellular fate of cholera toxin subunit b-modified mesoporous silica nanoparticle-supported lipid bilayers (aka protocells) in motoneurons","volume":"14","author":"Durfee","year":"2018","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0006-8993(86)91199-6","article-title":"Fluoro-Gold: A new fluorescent retrograde axonal tracer with numerous unique properties","volume":"377","author":"Schmued","year":"1986","journal-title":"Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lai, B.Q., Qiu, X.C., Zhang, K., Zhang, R.Y., Jin, H., Li, G., Shen, H.Y., Wu, J.L., Ling, E.A., and Zeng, Y.S. (2015). Cholera Toxin B Subunit Shows Transneuronal Tracing after Injection in an Injured Sciatic Nerve. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144030"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00429-003-0357-y","article-title":"Cells of origin of vagal motor neurons projecting to different parts of the stomach in the rat: Confocal laser scanning and electron microscopic study","volume":"207","author":"Hayakawa","year":"2003","journal-title":"Anat. Embryol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.exer.2015.10.004","article-title":"Neuroprotective effect of 4-(Phenylsulfanyl)butan-2-one on optic nerve crush model in rats","volume":"143","author":"Chien","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1167\/iovs.13-12811","article-title":"Evaluation of retinal nerve fiber layer thickness and axonal transport 1 and 2 weeks after 8 hours of acute intraocular pressure elevation in rats","volume":"55","author":"Abbott","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.actbio.2019.11.045","article-title":"Red fluorescent AuNDs with conjugation of cholera toxin subunit B (CTB) for extended-distance retro-nerve transporting and long-time neural tracing","volume":"102","author":"Zhao","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/0304-3940(92)90216-T","article-title":"Demonstration of transganglionically transported choleragenoid in rat spinal cord by immunofluorescence cytochemistry","volume":"145","author":"Rosario","year":"1992","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.brainres.2008.07.049","article-title":"Automated characterization of nerve fibers labeled fluorescently: Determination of size, class and spatial distribution","volume":"1233","author":"Prodanov","year":"2008","journal-title":"Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"104948","DOI":"10.1016\/j.chemphyslip.2020.104948","article-title":"Effects of lipid composition in cationic liposomes on suppression of mast cell activation","volume":"231","author":"Inoh","year":"2020","journal-title":"Chem. Phys. Lipids"},{"key":"ref_42","first-page":"230","article-title":"Gene transfection efficiency into dendritic cells is influenced by the size of cationic liposomes\/DNA complexes","volume":"102","author":"Inoh","year":"2017","journal-title":"Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12735","DOI":"10.1021\/acs.langmuir.0c02491","article-title":"Physicochemical Characterization of Liposomes That Mimic the Lipid Composition of Exosomes for Effective Intracellular Trafficking","volume":"36","author":"Yoshida","year":"2020","journal-title":"Langmuir ACS J. Surf. Colloids"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/cyto.a.22305","article-title":"Sulfocerebrosides upregulate liposome uptake in human astrocytes without inducing a proinflammatory response","volume":"83","author":"Suesca","year":"2013","journal-title":"Cytometry A"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1021\/mp500704e","article-title":"Influence of Endosomal Escape and Degradation of \u03b1-Galactosylceramide Loaded Liposomes on CD1d Antigen Presentation","volume":"12","author":"Nakamura","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1016\/j.xphs.2016.03.002","article-title":"A Dual-Ligand Liposomal System Composed of a Cell-Penetrating Peptide and a Mitochondrial RNA Aptamer Synergistically Facilitates Cellular Uptake and Mitochondrial Targeting","volume":"105","author":"Yamada","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jconrel.2016.12.038","article-title":"An intraocular drug delivery system using targeted nanocarriers attenuates retinal ganglion cell degeneration","volume":"247","author":"Zhao","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jconrel.2013.12.007","article-title":"Enhanced endosomal\/lysosomal escape by distearoyl phosphoethanolamine-polycarboxybetaine lipid for systemic delivery of siRNA","volume":"176","author":"Li","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ijpharm.2007.12.003","article-title":"Octaarginine-modified liposomes: Enhanced cellular uptake and controlled intracellular trafficking","volume":"354","author":"Khalil","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1021\/acs.accounts.5b00480","article-title":"Fighting Cholera One-on-One: The Development and Efficacy of Multivalent Cholera-Toxin-Binding Molecules","volume":"49","author":"Zuilhof","year":"2016","journal-title":"Acc. Chem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/j.xphs.2020.02.007","article-title":"Distribution of BCG-CWS-Loaded Nanoparticles in the Spleen After Intravenous Injection Affects Cytotoxic T Lymphocyte Activity","volume":"109","author":"Masuda","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7511","DOI":"10.1038\/s41598-020-64322-8","article-title":"Validation of a mitochondrial RNA therapeutic strategy using fibroblasts from a Leigh syndrome patient with a mutation in the mitochondrial ND3 gene","volume":"10","author":"Yamada","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1038\/mt.2008.122","article-title":"Efficient MHC class I presentation by controlled intracellular trafficking of antigens in octaarginine-modified liposomes","volume":"16","author":"Nakamura","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"0208051","DOI":"10.1115\/1.4037886","article-title":"Kinesin and Dynein Mechanics: Measurement Methods and Research Applications","volume":"140","author":"Abraham","year":"2018","journal-title":"J. Biomech. Eng."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1242\/dev.101.4.697","article-title":"A study in developing visual systems with a new method of staining neurones and their processes in fixed tissue","volume":"101","author":"Godement","year":"1987","journal-title":"Development"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/0896-6273(93)90110-D","article-title":"Gradual loss of synaptic cartels precedes axon withdrawal at developing neuromuscular junctions","volume":"11","author":"Chua","year":"1993","journal-title":"Neuron"},{"key":"ref_58","unstructured":"Muzio, M.R., and Cascella, M. (2021). Histology, Axon. StatPearls, StatPearls Publishing LLC."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/dneu.20859","article-title":"Compartmentalization within neurites: Its mechanisms and implications","volume":"71","author":"Katsuki","year":"2011","journal-title":"Dev. Neurobiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Aravamudhan, P., Raghunathan, K., Konopka-Anstadt, J., Pathak, A., Sutherland, D.M., Carter, B.D., and Dermody, T.S. (2020). Reovirus uses macropinocytosis-mediated entry and fast axonal transport to infect neurons. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008380"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1055\/s-0036-1586263","article-title":"Neuromuscular Diseases","volume":"36","author":"Morrison","year":"2016","journal-title":"Semin. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/j.1469-7580.2009.01072.x","article-title":"A comparative analysis of the encapsulated end-organs of mammalian skeletal muscles and of their sensory nerve endings","volume":"214","author":"Banks","year":"2009","journal-title":"J. Anat."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev.neuro.26.041002.131412","article-title":"The synaptic vesicle cycle","volume":"27","author":"Sudhof","year":"2004","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1471-4159.2006.03695.x","article-title":"The \u201cins\u201d and \u201couts\u201d of the high-affinity choline transporter CHT1","volume":"97","author":"Ribeiro","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1113\/jphysiol.2003.049221","article-title":"Endocytosis at the synaptic terminal","volume":"553","author":"Royle","year":"2003","journal-title":"J. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.neuron.2010.09.039","article-title":"Molecular motors in neurons: Transport mechanisms and roles in brain function, development, and disease","volume":"68","author":"Hirokawa","year":"2010","journal-title":"Neuron"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1128\/mr.58.1.94-144.1994","article-title":"Gas vesicles","volume":"58","author":"Walsby","year":"1994","journal-title":"Microbiol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0304-4157(87)90017-7","article-title":"Lipid intermolecular hydrogen bonding: Influence on structural organization and membrane function","volume":"906","author":"Boggs","year":"1987","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1021\/acs.molpharmaceut.8b00776","article-title":"GM1-Binding Conjugates To Improve Intestinal Permeability","volume":"16","author":"Melkoumov","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e00401-12","DOI":"10.1128\/mBio.00401-12","article-title":"A single native ganglioside GM1-binding site is sufficient for cholera toxin to bind to cells and complete the intoxication pathway","volume":"3","author":"Jobling","year":"2012","journal-title":"mBio"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ijpharm.2009.11.005","article-title":"Intracellular fate of octaarginine-modified liposomes in polarized MDCK cells","volume":"386","author":"Fujiwara","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1074\/jbc.M503202200","article-title":"High density of octaarginine stimulates macropinocytosis leading to efficient intracellular trafficking for gene expression","volume":"281","author":"Khalil","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1073\/pnas.1515526113","article-title":"Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration","volume":"113","author":"Sellers","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","first-page":"8","article-title":"Membrane translocation of arginine-rich cell-penetrating peptides","volume":"89","author":"Futaki","year":"2017","journal-title":"Seikagaku. J. Jpn. Biochem. Soc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nm.2107","article-title":"Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury","volume":"16","author":"Boulenguez","year":"2010","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1038\/nm.3356","article-title":"Chloride extrusion enhancers as novel therapeutics for neurological diseases","volume":"19","author":"Gagnon","year":"2013","journal-title":"Nat. Med."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Cappella, M., Ciotti, C., Cohen-Tannoudji, M., and Biferi, M.G. (2019). Gene Therapy for ALS-A Perspective. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184388"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"126950","DOI":"10.1016\/j.bmcl.2020.126950","article-title":"Development of novel small molecules for the treatment of ALS","volume":"30","author":"Mathew","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"102980","DOI":"10.1016\/j.ebiom.2020.102980","article-title":"Novel Selenium-based compounds with therapeutic potential for SOD1-linked amyotrophic lateral sclerosis","volume":"59","author":"Amporndanai","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_80","first-page":"137","article-title":"SMA: From gene discovery to gene therapy","volume":"36","author":"Barkats","year":"2020","journal-title":"Med. Sci. M\/S"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/0006-8993(86)90343-4","article-title":"Motor, sympathetic and sensory innervation of rat skeletal muscles","volume":"373","author":"Peyronnard","year":"1986","journal-title":"Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0006-8993(79)90938-7","article-title":"Localization of lumbar epaxial motoneurons in the rat","volume":"170","author":"Brink","year":"1979","journal-title":"Brain Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/12\/6661\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:31:53Z","timestamp":1760139113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/12\/6661"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,15]]},"references-count":82,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23126661"],"URL":"https:\/\/doi.org\/10.3390\/ijms23126661","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,15]]}}}