{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:07:05Z","timestamp":1773976025965,"version":"3.50.1"},"reference-count":87,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense Congressionally Directed Medical Research Programs Amyotrophic Lateral Sclerosis Research Program Therapeutic Idea Award","doi-asserted-by":"publisher","award":["W81XWH2210261"],"award-info":[{"award-number":["W81XWH2210261"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Georgia","award":["W81XWH2210261"],"award-info":[{"award-number":["W81XWH2210261"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a complex neuromuscular disease characterized by progressive motor neuron degeneration, neuromuscular junction dismantling, and muscle wasting. The pathological and therapeutic studies of ALS have long been neurocentric. However, recent insights have highlighted the significance of peripheral tissue, particularly skeletal muscle, in disease pathology and treatment. This is evidenced by restricted ALS-like muscle atrophy, which can retrogradely induce neuromuscular junction and motor neuron degeneration. Moreover, therapeutics targeting skeletal muscles can effectively decelerate disease progression by modulating muscle satellite cells for muscle repair, suppressing inflammation, and promoting the recovery or regeneration of the neuromuscular junction. This review summarizes and discusses therapeutic strategies targeting skeletal muscles for ALS treatment. It aims to provide a comprehensive reference for the development of novel therapeutics targeting skeletal muscles, potentially ameliorating the progression of ALS.<\/jats:p>","DOI":"10.3390\/biom14070878","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T14:26:50Z","timestamp":1721744810000},"page":"878","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Therapeutics Targeting Skeletal Muscle in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Jinghui","family":"Gao","sequence":"first","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elijah","family":"Sterling","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5974-8601","authenticated-orcid":false,"given":"Rachel","family":"Hankin","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aria","family":"Sikal","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8851-7885","authenticated-orcid":false,"given":"Yao","family":"Yao","sequence":"additional","affiliation":[{"name":"Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1136\/jnnp.2010.224501","article-title":"Rate of familial amyotrophic lateral sclerosis: A systematic review and meta-analysis","volume":"82","author":"Byrne","year":"2011","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.pneurobio.2016.05.004","article-title":"ALS: A bucket of genes, environment, metabolism and unknown ingredients","volume":"142","author":"Poza","year":"2016","journal-title":"Prog. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jns.2019.02.030","article-title":"Genetics of amyotrophic lateral sclerosis: A review","volume":"399","author":"Mathis","year":"2019","journal-title":"J. Neurol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/35097565","article-title":"From Charcot to Lou Gehrig: Deciphering selective motor neuron death in ALS","volume":"2","author":"Cleveland","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrneurol.2011.150","article-title":"Clinical genetics of amyotrophic lateral sclerosis: What do we really know?","volume":"7","author":"Andersen","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.expneurol.2014.05.015","article-title":"Glial cells in amyotrophic lateral sclerosis","volume":"262","author":"Philips","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Moloney, E.B., de Winter, F., and Verhaagen, J. (2014). ALS as a distal axonopathy: Molecular mechanisms affecting neuromuscular junction stability in the presymptomatic stages of the disease. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00252"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E756","DOI":"10.1073\/pnas.1222361110","article-title":"Intricate interplay between astrocytes and motor neurons in ALS","volume":"110","author":"Phatnani","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1093\/brain\/awad202","article-title":"Skeletal muscle in amyotrophic lateral sclerosis","volume":"146","author":"Shefner","year":"2023","journal-title":"Brain"},{"key":"ref_10","first-page":"61","article-title":"Riluzole: Real-world evidence supports significant extension of median survival times in patients with amyotrophic lateral sclerosis","volume":"7","author":"Hinchcliffe","year":"2017","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cho, H., and Shukla, S. (2021). Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis. Pharmaceuticals, 14.","DOI":"10.3390\/ph14010029"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1056\/NEJMoa1916945","article-title":"Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis","volume":"383","author":"Paganoni","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0303-8467(75)80050-3","article-title":"The case of the saltimbanque Prosper Lecomte. A contribution to the study of the history of progressive muscular atrophy (Aran-Duchenne) and amyotrophic lateral sclerosis (Charcot)","volume":"78","author":"Veltema","year":"1975","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3109\/00207459108985432","article-title":"Muscle morphometry in amyotrophic lateral sclerosis","volume":"58","author":"Iwasaki","year":"1991","journal-title":"Int. J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s40478-014-0165-z","article-title":"Mitochondrial abnormalities and low grade inflammation are present in the skeletal muscle of a minority of patients with amyotrophic lateral sclerosis; an observational myopathology study","volume":"2","author":"King","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1212\/WNL.24.9.834","article-title":"Serum creatine phosphokinase in amyotrophic lateral sclerosis. Correlation with sex, duration, and skeletal muscle biopsy","volume":"24","author":"Amrit","year":"1974","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1378\/chest.103.2.508","article-title":"Pulmonary-Function at Diagnosis of Amyotrophic-Lateral-Sclerosis\u2014Rate of Deterioration","volume":"103","author":"Schiffman","year":"1993","journal-title":"Chest"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5527","DOI":"10.1113\/JP278835","article-title":"The role of skeletal muscle in amyotrophic lateral sclerosis: A \u2018dying-back\u2019 or \u2018dying-forward\u2019 phenomenon?","volume":"597","author":"Tsitkanou","year":"2019","journal-title":"J. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/nrn1788","article-title":"Axon degeneration mechanisms: Commonality amid diversity","volume":"6","author":"Coleman","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1523\/JNEUROSCI.20-07-02534.2000","article-title":"Early and selective loss of neuromuscular synapse subtypes with low sprouting competence in motoneuron diseases","volume":"20","author":"Frey","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/s12031-010-9467-1","article-title":"The \u201cDying-Back\u201d Phenomenon of Motor Neurons in ALS","volume":"43","author":"Melamed","year":"2011","journal-title":"J. Mol. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4825","DOI":"10.1523\/JNEUROSCI.22-12-04825.2002","article-title":"Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease","volume":"22","author":"Lino","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Martin, L.J., and Wong, M. (2020). Skeletal Muscle-Restricted Expression of Human SOD1 in Transgenic Mice Causes a Fatal ALS-Like Syndrome. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.592851"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1093\/hmg\/ddq106","article-title":"Skeletal muscle-restricted expression of human SOD1 causes motor neuron degeneration in transgenic mice","volume":"19","author":"Wong","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/2044-5040-1-3","article-title":"Muscle atrophy induced by SOD1G93A expression does not involve the activation of caspase in the absence of denervation","volume":"1","author":"Dobrowolny","year":"2011","journal-title":"Skelet. Muscle"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00401-009-0536-x","article-title":"Synaptic degeneration in Alzheimer\u2019s disease","volume":"118","author":"Arendt","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s disease: Mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.1074069","article-title":"Alzheimer\u2019s disease is a synaptic failure","volume":"298","author":"Selkoe","year":"2002","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.9.2.493","article-title":"Satellite cell of skeletal muscle fibers","volume":"9","author":"Mauro","year":"1961","journal-title":"J. Biophys. Biochem. Cytol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.semcdb.2017.11.011","article-title":"Function of the myogenic regulatory factors Myf5, MyoD, Myogenin and MRF4 in skeletal muscle, satellite cells and regenerative myogenesis","volume":"72","author":"Zammit","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S0092-8674(00)00066-0","article-title":"Pax7 is required for the specification of myogenic satellite cells","volume":"102","author":"Seale","year":"2000","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0092-8674(00)80189-0","article-title":"Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and Myf-5 act upstream of MyoD","volume":"89","author":"Tajbakhsh","year":"1997","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/aja.1001930106","article-title":"Myod and Myogenin Are Coexpressed in Regenerating Skeletal-Muscle of the Mouse","volume":"193","author":"Fuchtbauer","year":"1992","journal-title":"Dev. Dynam"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e09221","DOI":"10.7554\/eLife.09221","article-title":"Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions","volume":"4","author":"Liu","year":"2015","journal-title":"eLife"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e26464","DOI":"10.7554\/eLife.26464","article-title":"Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration","volume":"6","author":"Liu","year":"2017","journal-title":"eLife"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3109\/17482968.2011.566618","article-title":"Abnormalities of satellite cells function in amyotrophic lateral sclerosis","volume":"12","author":"Pradat","year":"2011","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3109\/01913123.2014.937842","article-title":"Skeletal muscle satellite cells in amyotrophic lateral sclerosis","volume":"38","author":"Scaramozza","year":"2014","journal-title":"Ultrastruct. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101087","DOI":"10.1016\/j.isci.2020.101087","article-title":"Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1 Mice Predates Disease Onset and Is A Promising Therapeutic Target","volume":"23","author":"Scaricamazza","year":"2020","journal-title":"iScience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/bpa.12774","article-title":"P2X7 activation enhances skeletal muscle metabolism and regeneration in SOD1G93A mouse model of amyotrophic lateral sclerosis","volume":"30","author":"Fabbrizio","year":"2020","journal-title":"Brain Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00018-021-04070-8","article-title":"Contingent intramuscular boosting of P2XR7 axis improves motor function in transgenic ALS mice","volume":"79","author":"Fabbrizio","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11302-015-9445-8","article-title":"Up-regulation of P2X7 receptors mediating proliferation of Schwann cells after sciatic nerve injury","volume":"11","author":"Song","year":"2015","journal-title":"Purinergic Signal"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1083\/jcb.200407021","article-title":"Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model","volume":"168","author":"Dobrowolny","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e23068","DOI":"10.1096\/fj.202300573R","article-title":"Therapy of autoimmune inflammation in sporadic amyotrophic lateral sclerosis: Dimethyl fumarate and H-151 downregulate inflammatory cytokines in the cGAS-STING pathway","volume":"37","author":"Zamiri","year":"2023","journal-title":"Faseb J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10974-019-09511-3","article-title":"The role of satellite and other functional cell types in muscle repair and regeneration","volume":"40","author":"Chen","year":"2019","journal-title":"J. Muscle Res. Cell M."},{"key":"ref_45","first-page":"25","article-title":"Skeletal muscle regeneration is modulated by inflammation","volume":"13","author":"Yang","year":"2018","journal-title":"J. Orthop. Transl."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Garabuczi, \u00c9., Tarban, N., Fige, \u00c9., Patsalos, A., Hal\u00e1sz, L., Szendi-Szatm\u00e1ri, T., Sarang, Z., Kir\u00e1ly, R., and Szondy, Z. (2023). Nur77 and PPAR\u03b3 regulate transcription and polarization in distinct subsets of M2-like reparative macrophages during regenerative inflammation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1139204"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.expneurol.2016.01.008","article-title":"Macrophage-mediated inflammation and glial response in the skeletal muscle of a rat model of familial amyotrophic lateral sclerosis (ALS)","volume":"277","author":"Macrander","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/nan.12483","article-title":"Expression profile of pattern recognition receptors in skeletal muscle of SOD1 amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients","volume":"44","author":"Lehmann","year":"2018","journal-title":"Neuropath. Appl. Neuro"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13395-015-0048-4","article-title":"Upregulated IL-1\u03b2 in dysferlin-deficient muscle attenuates regeneration by blunting the response to pro-inflammatory macrophages","volume":"5","author":"Cohen","year":"2015","journal-title":"Skelet. Muscle"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"E45","DOI":"10.1152\/ajpendo.1997.272.1.E45","article-title":"Skeletal muscle myosin heavy-chain synthesis rate in healthy humans","volume":"272","author":"Balagopal","year":"1997","journal-title":"Am. J. Physiol. ndocrinol. Metab."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ji, Y.A., Li, M., Chang, M.Y., Liu, R.Q., Qiu, J.Y., Wang, K.X., Deng, C.Y., Shen, Y.T., Zhu, J.W., and Wang, W. (2022). Inflammation: Roles in Skeletal Muscle Atrophy. Antioxidants, 11.","DOI":"10.3390\/antiox11091686"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Fabbrizio, P., Margotta, C., D\u2019Agostino, J., Suanno, G., Quetti, L., Bendotti, C., and Nardo, G. (2023). Intramuscular IL-10 Administration Enhances the Activity of Myogenic Precursor Cells and Improves Motor Function in ALS Mouse Model. Cells, 12.","DOI":"10.3390\/cells12071016"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nri.2016.150","article-title":"Regulation of muscle growth and regeneration by the immune system","volume":"17","author":"Tidball","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1016\/j.ymthe.2022.04.018","article-title":"Boosting the peripheral immune response in the skeletal muscles improved motor function in ALS transgenic mice","volume":"30","author":"Trolese","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Slater, C.R. (2017). The Structure of Human Neuromuscular Junctions: Some Unanswered Molecular Questions. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102183"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev.neuro.22.1.389","article-title":"Development of the vertebrate neuromuscular junction","volume":"22","author":"Sanes","year":"1999","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1242\/jcs.031047","article-title":"Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions","volume":"121","author":"Court","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Cruz, P.M.R., Cossins, J., Beeson, D., and Vincent, A. (2020). The Neuromuscular Junction in Health and Disease: Molecular Mechanisms Governing Synaptic Formation and Homeostasis. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.610964"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.expneurol.2003.10.004","article-title":"Amyotrophic lateral sclerosis is a distal axonopathy: Evidence in mice and man","volume":"185","author":"Fischer","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1038\/sj.embor.7400826","article-title":"The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic lateral sclerosis model","volume":"7","author":"Jokic","year":"2006","journal-title":"Embo Rep."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Badu-Mensah, A., Guo, X.F., Nimbalkar, S., Cai, Y.Q., and Hickman, J.J. (2022). ALS mutations in both human skeletal muscle and motoneurons differentially affects neuromuscular junction integrity and function. Biomaterials, 289.","DOI":"10.1016\/j.biomaterials.2022.121752"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Geijo-Barrientos, E., Pastore-Olmedo, C., De Mingo, P., Blanquer, M., Espuch, J.G., Iniesta, F., Iniesta, N.G., Garc\u00eda-Hern\u00e1ndez, A., Mart\u00edn-Estefan\u00eda, C., and Barrios, L. (2020). Intramuscular Injection of Bone Marrow Stem Cells in Amyotrophic Lateral Sclerosis Patients: A Randomized Clinical Trial. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00195"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1038\/s41598-020-58221-1","article-title":"Repeated intramuscular transplantations of hUCB-MSCs improves motor function and survival in the SOD1 G93A mice through activation of AMPK","volume":"10","author":"Kook","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1038\/mt.2008.197","article-title":"Direct Muscle Delivery of GDNF with Human Mesenchymal Stem Cells Improves Motor Neuron Survival and Function in a Rat Model of Familial ALS","volume":"16","author":"Suzuki","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/mt.2013.108","article-title":"Synergistic Effects of GDNF and VEGF on Lifespan and Disease Progression in a Familial ALS Rat Model","volume":"21","author":"Krakora","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1126\/science.7973664","article-title":"Gdnf\u2014A Potent Survival Factor for Motoneurons Present in Peripheral-Nerve and Muscle","volume":"266","author":"Henderson","year":"1994","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nature02544","article-title":"VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model","volume":"429","author":"Azzouz","year":"2004","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9229","DOI":"10.1073\/pnas.93.17.9229","article-title":"Cell death in the Schwann cell lineage and its regulation by neuregulin","volume":"93","author":"Syroid","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1126\/science.276.5312.599","article-title":"Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivo","volume":"276","author":"Sandrock","year":"1997","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1242\/dev.126.4.781","article-title":"Expression patterns of transmembrane and released forms of neuregulin during spinal cord and neuromuscular synapse development","volume":"126","author":"Loeb","year":"1999","journal-title":"Development"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"M\u00f3dol-Caballero, G., Herrando-Grabulosa, M., Garc\u00eda-Lareu, B., Solanes, N., Verd\u00e9s, S., Osta, R., Francos-Quijorna, I., L\u00f3pez-Vales, R., Calvo, A.C., and Bosch, A. (2020). Gene therapy for overexpressing Neuregulin 1 type I in skeletal muscles promotes functional improvement in the SOD1 ALS mice. Neurobiol. Dis., 137.","DOI":"10.1016\/j.nbd.2020.104793"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"101385","DOI":"10.1016\/j.isci.2020.101385","article-title":"Gene Therapy Enhances Neuromuscular Junction Innervation and Motor Function in Aged Mice","volume":"23","author":"Ueta","year":"2020","journal-title":"iScience"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.abb.2019.01.024","article-title":"Dysregulated mitochondrial Ca and ROS signaling in skeletal muscle of ALS mouse model","volume":"663","author":"Zhou","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Bernardini, C., Censi, F., Lattanzi, W., Barba, M., Calcagnini, G., Giuliani, A., Tasca, G., Sabatelli, M., Ricci, E., and Michetti, F. (2013). Mitochondrial Network Genes in the Skeletal Muscle of Amyotrophic Lateral Sclerosis Patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057739"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.nbd.2012.08.015","article-title":"Disruption of skeletal muscle mitochondrial network genes and miRNAs in amyotrophic lateral sclerosis","volume":"49","author":"Russell","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.neulet.2016.04.065","article-title":"Oxidative stress and mitochondrial damage in the pathogenesis of ALS: New perspectives","volume":"636","author":"Bozzo","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.freeradbiomed.2010.01.014","article-title":"Oxidative stress in skeletal muscle stimulates early expression of Rad in a mouse model of amyotrophic lateral sclerosis","volume":"48","author":"Halter","year":"2010","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"M\u00e9ndez-L\u00f3pez, I., Sancho-Bielsa, F.J., Engel, T., Garc\u00eda, A.G., and Pad\u00edn, J.F. (2021). Progressive Mitochondrial SOD1 Accumulation Causes Severe Structural, Metabolic and Functional Aberrations through OPA1 Down-Regulation in a Mouse Model of Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158194"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1080\/14737175.2019.1581610","article-title":"Edaravone for the treatment of amyotrophic lateral sclerosis","volume":"19","author":"Yoshino","year":"2019","journal-title":"Expert. Rev. Neurother."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Cha, S.J., and Kim, K. (2022). Effects of the Edaravone, a Drug Approved for the Treatment of Amyotrophic Lateral Sclerosis, on Mitochondrial Function and Neuroprotection. Antioxidants, 11.","DOI":"10.3390\/antiox11020195"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12964-018-0294-2","article-title":"Four-octyl itaconate activates Keap1-Nrf2 signaling to protect neuronal cells from hydrogen peroxide","volume":"16","author":"Liu","year":"2018","journal-title":"Cell Commun. Signal"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.apsb.2022.07.019","article-title":"Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis","volume":"13","author":"Zhou","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"101536","DOI":"10.1016\/j.molmet.2022.101536","article-title":"Pharmacological inhibition of ALCAT1 mitigates amyotrophic lateral sclerosis by attenuating SOD1 protein aggregation","volume":"63","author":"Liu","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.clinthera.2016.12.014","article-title":"Target Intestinal Microbiota to Alleviate Disease Progression in Amyotrophic Lateral Sclerosis","volume":"39","author":"Zhang","year":"2017","journal-title":"Clin. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Li, A., Li, X.J., Yi, J.X., Ma, J.J., and Zhou, J.S. (2021). Butyrate Feeding Reverses CypD-Related Mitoflash Phenotypes in Mouse Myofibers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147412"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Li, X.J., Dong, L., Li, A., Yi, J.X., Brotto, M., and Zhou, J.S. (2022). Butyrate Ameliorates Mitochondrial Respiratory Capacity of The Motor-Neuron-like Cell Line NSC34-G93A, a Cellular Model for ALS. Biomolecules, 12.","DOI":"10.3390\/biom12020333"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"RP92644","DOI":"10.7554\/eLife.92644.4","article-title":"Distinct transcriptomic profile of satellite cells contributes to preservation of neuromuscular junctions in extraocular muscles of ALS mice","volume":"12","author":"Li","year":"2024","journal-title":"eLife"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/7\/878\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:20:50Z","timestamp":1760109650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/7\/878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,22]]},"references-count":87,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["biom14070878"],"URL":"https:\/\/doi.org\/10.3390\/biom14070878","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,22]]}}}