{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:19:34Z","timestamp":1789165174800,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>TDP\u201043 pathology is broadly observed in the cerebral cortex of patients with amyotrophic lateral sclerosis (ALS). RNS60, an experimental treatment for acute ischemic stroke and ALS, enhanced mitochondrial biogenesis and function in other preclinical models. We investigated whether RNS60 improved mitochondrial stability and upper motor neuron (UMN) health in a TDP\u201043 mouse model of ALS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      prpTDP\u201043\n                      <jats:sup>A315T<\/jats:sup>\n                      \u2010UeGFP mice, in which UMNs express green fluorescent protein (eGFP), and WT\u2010UeGFP mice were treated with RNS60 or placebo intraperitoneally every other day from post\u2010natal day (P) 30 until P90. Astrogliosis and microgliosis in brain and spinal cord were quantified by immunocytochemistry. Mitochondrial ultrastructure was studied via electron microscopy, and mitochondrial function was assessed using flow cytometry. Neuromuscular junction (NMJ) integrity was assessed in gastrocnemius, tibialis, and diaphragm muscles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RNS60 treatment reduced defective mitochondria in UMNs (prpTDP\u201043\n                      <jats:sup>A315T<\/jats:sup>\n                      \u2009+\u2009vehicle: 53.2%\u2009\u00b1\u20090.71%; prpTDP\u201043\n                      <jats:sup>A315T<\/jats:sup>\n                      \u2009+\u2009RNS60: 19.6%\u2009\u00b1\u20091.4%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001) and spinal motor neurons (prpTDP\u201043\n                      <jats:sup>A315T<\/jats:sup>\n                      \u2009+\u2009vehicle: 70.1%\u2009\u00b1\u20090.4.48%; prpTDP\u201043\n                      <jats:sup>A315T<\/jats:sup>\n                      \u2009+\u2009RNS60: 33.5%\u2009\u00b1\u20094.43%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). It increased mitochondrial membrane polarization (prpTDP\u201043\n                      <jats:sup>A315T<\/jats:sup>\n                      \u2010UeGFP\u2009+\u2009vehicle: 7184\u2009\u00b1\u20091689 mean intensity; prpTDP\u201043\n                      <jats:sup>A315T<\/jats:sup>\n                      \u2010UeGFP+RNS60: 22120\u2009\u00b1\u20094818 mean intensity,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.032), reduced the extent of astrogliosis and microgliosis in motor cortex and spinal cord, protected UMNs compared to placebo, and enhanced the proportion of intact NMJs in leg and diaphragm muscles (prpTDP\u201043\n                      <jats:sup>A315T<\/jats:sup>\n                      \u2010UeGFP\u2009+\u2009vehicle: 29.6%\u2009\u00b1\u20093.6%; prpTDP\u201043\n                      <jats:sup>A315T<\/jats:sup>\n                      \u2010UeGFP\u2009+\u2009RNS60: 64.3%\u2009\u00b1\u20094.4%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These results suggest that RNS60 treatment promotes motor neuron health in ALS by protecting mitochondrial structure and function, preserving NMJ integrity, and reducing gliosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.70289","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T07:08:54Z","timestamp":1780556934000},"page":"463-473","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Effects of\n                    <scp>RNS60<\/scp>\n                    in\n                    <scp>TDP<\/scp>\n                    \u201043 Pathology\u2010Associated Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"74","author":[{"given":"Danny R.","family":"Vesevick","sequence":"first","affiliation":[{"name":"Davee Department of Neurology and Clinical Neurological Sciences Northwestern University, Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supurna","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Revalesio  Tacoma Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0715-5652","authenticated-orcid":false,"given":"Andreas","family":"Kalmes","sequence":"additional","affiliation":[{"name":"Revalesio  Tacoma Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Hande","family":"Ozdinler","sequence":"additional","affiliation":[{"name":"Davee Department of Neurology and Clinical Neurological Sciences Northwestern University, Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Les Turner ALS Center Northwestern University, Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Chemistry of Life Processes Institute Northwestern University  Evanston Illinois USA"},{"name":"Robert H. Lurie Comprehensive Cancer Center Northwestern University, Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Mesulam Center for Cognitive Neurology and Alzheimer's Disease Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6595-3051","authenticated-orcid":false,"given":"Mukesh","family":"Gautam","sequence":"additional","affiliation":[{"name":"Davee Department of Neurology and Clinical Neurological Sciences Northwestern University, Feinberg School of Medicine  Chicago Illinois USA"},{"name":"Les Turner ALS Center Northwestern University, Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.07.033"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(25)00109-7"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1142617"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2019.103396"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.04.053"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06953-y"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007947"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt319"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.020"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1934-8"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1589-y"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2787-12.2013"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-062111-150527"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.31.060407.125547"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11050619"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.125.051179"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15573"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.08.044"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0295504"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-017-9771-4"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103606"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2214-z"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113279"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep30020"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1101-0"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-013-9503-3"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14399-5"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908767106"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22157781"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000001279"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106022"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.07.019"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.01.027"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-021-00303-4"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.13463"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2012.07.003"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2016.03.003"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-022-00331-z"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.02.028"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00143"}],"container-title":["Muscle &amp; 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