{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:01:54Z","timestamp":1791054114025,"version":"4.1.0"},"reference-count":102,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kazan State Medical University","award":["1\/22-3"],"award-info":[{"award-number":["1\/22-3"]}]},{"name":"Kazan State Medical University","award":["21-14-00044"],"award-info":[{"award-number":["21-14-00044"]}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["1\/22-3"],"award-info":[{"award-number":["1\/22-3"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-14-00044"],"award-info":[{"award-number":["21-14-00044"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is manifested as skeletal muscle denervation, loss of motor neurons and finally severe respiratory failure. Mutations of RNA-binding protein FUS are one of the common genetic reasons of ALS accompanied by a \u2018dying back\u2019 type of degeneration. Using fluorescent approaches and microelectrode recordings, the early structural and functional alterations in diaphragm neuromuscular junctions (NMJs) were studied in mutant FUS mice at the pre-onset stage. Lipid peroxidation and decreased staining with a lipid raft marker were found in the mutant mice. Despite the preservation of the end-plate structure, immunolabeling revealed an increase in levels of presynaptic proteins, SNAP-25 and synapsin 1. The latter can restrain Ca2+-dependent synaptic vesicle mobilization. Indeed, neurotransmitter release upon intense nerve stimulation and its recovery after tetanus and compensatory synaptic vesicle endocytosis were markedly depressed in FUS mice. There was a trend to attenuation of axonal [Ca2+]in increase upon nerve stimulation at 20 Hz. However, no changes in neurotransmitter release and the intraterminal Ca2+ transient in response to low frequency stimulation or in quantal content and the synchrony of neurotransmitter release at low levels of external Ca2+ were detected. At a later stage, shrinking and fragmentation of end plates together with a decrease in presynaptic protein expression and disturbance of the neurotransmitter release timing occurred. Overall, suppression of synaptic vesicle exo\u2013endocytosis upon intense activity probably due to alterations in membrane properties, synapsin 1 levels and Ca2+ kinetics could be an early sign of nascent NMJ pathology, which leads to neuromuscular contact disorganization.<\/jats:p>","DOI":"10.3390\/ijms24109022","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T02:28:42Z","timestamp":1684722522000},"page":"9022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Early Alterations in Structural and Functional Properties in the Neuromuscular Junctions of Mutant FUS Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Marat A.","family":"Mukhamedyarov","sequence":"first","affiliation":[{"name":"Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5625-8658","authenticated-orcid":false,"given":"Aydar N.","family":"Khabibrakhmanov","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venera F.","family":"Khuzakhmetova","sequence":"additional","affiliation":[{"name":"Kazan Institute of Biochemistry and Biophysics, Federal Research Center \u2018\u2018Kazan Scientific Center of RAS\u201d, 2\/31 Lobachevsky St., P.O. Box 30, Kazan 420111, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4789-1800","authenticated-orcid":false,"given":"Arthur R.","family":"Giniatullin","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia"},{"name":"Kazan Institute of Biochemistry and Biophysics, Federal Research Center \u2018\u2018Kazan Scientific Center of RAS\u201d, 2\/31 Lobachevsky St., P.O. Box 30, Kazan 420111, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guzalia F.","family":"Zakirjanova","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia"},{"name":"Kazan Institute of Biochemistry and Biophysics, Federal Research Center \u2018\u2018Kazan Scientific Center of RAS\u201d, 2\/31 Lobachevsky St., P.O. Box 30, Kazan 420111, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita V.","family":"Zhilyakov","sequence":"additional","affiliation":[{"name":"Kazan Institute of Biochemistry and Biophysics, Federal Research Center \u2018\u2018Kazan Scientific Center of RAS\u201d, 2\/31 Lobachevsky St., P.O. Box 30, Kazan 420111, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamilla A.","family":"Mukhutdinova","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6019-5514","authenticated-orcid":false,"given":"Dmitry V.","family":"Samigullin","sequence":"additional","affiliation":[{"name":"Kazan Institute of Biochemistry and Biophysics, Federal Research Center \u2018\u2018Kazan Scientific Center of RAS\u201d, 2\/31 Lobachevsky St., P.O. Box 30, Kazan 420111, Russia"},{"name":"Department of Radiophotonics and Microwave Technologies, Kazan National Research Technical University, 10 K. Marx St., Kazan 420111, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel N.","family":"Grigoryev","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey V.","family":"Zakharov","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia"},{"name":"Laboratory of Neurobiology, Kazan Federal University, Kazan 420008, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey L.","family":"Zefirov","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1432-3455","authenticated-orcid":false,"given":"Alexey M.","family":"Petrov","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology, Kazan State Medial University, 49 Butlerova St., Kazan 420012, Russia"},{"name":"Kazan Institute of Biochemistry and Biophysics, Federal Research Center \u2018\u2018Kazan Scientific Center of RAS\u201d, 2\/31 Lobachevsky St., P.O. Box 30, Kazan 420111, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2000133","DOI":"10.1002\/adtp.202000133","article-title":"A Human-Based Functional NMJ System for Personalized ALS Modeling and Drug Testing","volume":"3","author":"Guo","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1111\/joa.13463","article-title":"Small junction, big problems: Neuromuscular junction pathology in mouse models of amyotrophic lateral sclerosis (ALS)","volume":"241","author":"Alhindi","year":"2022","journal-title":"J. Anat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00401-017-1708-8","article-title":"Motor neuron vulnerability and resistance in amyotrophic lateral sclerosis","volume":"133","author":"Nijssen","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/hmg\/ddx415","article-title":"Mitochondrial abnormalities and disruption of the neuromuscular junction precede the clinical phenotype and motor neuron loss in hFUSWT transgenic mice","volume":"27","author":"So","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1000183","DOI":"10.3389\/fnmol.2022.1000183","article-title":"Synaptic dysfunction in ALS and FTD: Anatomical and molecular changes provide insights into mechanisms of disease","volume":"15","author":"Gelon","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1038\/s41593-019-0498-9","article-title":"FUS-mediated regulation of acetylcholine receptor transcription at neuromuscular junctions is compromised in amyotrophic lateral sclerosis","volume":"22","author":"Picchiarelli","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10465","DOI":"10.1038\/ncomms10465","article-title":"ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function","volume":"7","author":"Sharma","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1007\/s12035-021-02658-6","article-title":"Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis","volume":"59","author":"Verma","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_9","first-page":"551","article-title":"Amyotrophic Lateral Sclerosis: Modern Views on the Pathogenesis and Experimental Models","volume":"68","author":"Mukhamedyarov","year":"2018","journal-title":"Zhurnal Vyss. Nervn. Deyatelnosti Im. IP Pavlov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.neurol.2020.06.010","article-title":"FUS mutation is probably the most common pathogenic gene for JALS, especially sporadic JALS","volume":"177","author":"Chen","year":"2021","journal-title":"Rev. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s12015-022-10489-8","article-title":"Amyotrophic Lateral Sclerosis, FUS and Protein Synthesis Defects","volume":"19","author":"Assoni","year":"2023","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.cub.2005.01.058","article-title":"The RNA binding protein TLS is translocated to dendritic spines by mGluR5 activation and regulates spine morphology","volume":"15","author":"Fujii","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.neuron.2013.07.033","article-title":"Converging mechanisms in ALS and FTD: Disrupted RNA and protein homeostasis","volume":"79","author":"Ling","year":"2013","journal-title":"Neuron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13613","DOI":"10.1038\/s41598-021-93189-6","article-title":"Identification of a novel interaction of FUS and syntaphilin may explain synaptic and mitochondrial abnormalities caused by ALS mutations","volume":"11","author":"Salam","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1016\/j.stemcr.2021.03.029","article-title":"Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition","volume":"16","author":"Krasnow","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/76615","article-title":"Proteomic analysis of NMDA receptor-adhesion protein signaling complexes","volume":"3","author":"Husi","year":"2000","journal-title":"Nat. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nrneurol.2014.184","article-title":"The phenotypic variability of amyotrophic lateral sclerosis","volume":"10","author":"Swinnen","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/cphy.c180012","article-title":"Evolution and Functional Differentiation of the Diaphragm Muscle of Mammals","volume":"9","author":"Fogarty","year":"2019","journal-title":"Compr. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.resp.2011.10.015","article-title":"Structure-activity relationships in rodent diaphragm muscle fibers vs. neuromuscular junctions","volume":"180","author":"Sieck","year":"2012","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rocha, M.C., Pousinha, P.A., Correia, A.M., Sebastiao, A.M., and Ribeiro, J.A. (2013). Early changes of neuromuscular transmission in the SOD1(G93A) mice model of ALS start long before motor symptoms onset. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073846"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119300","DOI":"10.1016\/j.lfs.2021.119300","article-title":"Early differences in membrane properties at the neuromuscular junctions of ALS model mice: Effects of 25-hydroxycholesterol","volume":"273","author":"Zakyrjanova","year":"2021","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s11302-015-9465-4","article-title":"Presymptomatic and symptomatic ALS SOD1(G93A) mice differ in adenosine A1 and A2A receptor-mediated tonic modulation of neuromuscular transmission","volume":"11","author":"Nascimento","year":"2015","journal-title":"Purinergic Signal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1523\/JNEUROSCI.1379-14.2015","article-title":"Early and persistent abnormal decoding by glial cells at the neuromuscular junction in an ALS model","volume":"35","author":"Arbour","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yi, J., Li, A., Li, X., Park, K., Zhou, X., Yi, F., Xiao, Y., Yoon, D., Tan, T., and Ostrow, L.W. (2021). MG53 Preserves Neuromuscular Junction Integrity and Alleviates ALS Disease Progression. Antioxidants, 10.","DOI":"10.3390\/antiox10101522"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25266","DOI":"10.1074\/jbc.M113.492017","article-title":"Fused in sarcoma (FUS) protein lacking nuclear localization signal (NLS) and major RNA binding motifs triggers proteinopathy and severe motor phenotype in transgenic mice","volume":"288","author":"Shelkovnikova","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10048-018-0553-9","article-title":"FUS(1-359) transgenic mice as a model of ALS: Pathophysiological and molecular aspects of the proteinopathy","volume":"19","author":"Funikov","year":"2018","journal-title":"Neurogenetics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113986","DOI":"10.1016\/j.biopha.2022.113986","article-title":"In FUS [1-359]-tg mice O,S-dibenzoyl thiamine reduces muscle atrophy, decreases glycogen synthase kinase 3 beta, and normalizes the metabolome","volume":"156","author":"Probert","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sambon, M., Gorlova, A., Demelenne, A., Alhama-Riba, J., Coumans, B., Lakaye, B., Wins, P., Fillet, M., Anthony, D.C., and Strekalova, T. (2020). Dibenzoylthiamine Has Powerful Antioxidant and Anti-Inflammatory Properties in Cultured Cells and in Mouse Models of Stress and Neurodegeneration. Biomedicines, 8.","DOI":"10.3390\/biomedicines8090361"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"dmm040238","DOI":"10.1242\/dmm.040238","article-title":"Vascular regression precedes motor neuron loss in the FUS (1-359) ALS mouse model","volume":"12","author":"Crivello","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12607","DOI":"10.1111\/gbb.12607","article-title":"Behavioural impairments in mice of a novel FUS transgenic line recapitulate features of frontotemporal lobar degeneration","volume":"18","author":"Lysikova","year":"2019","journal-title":"Genes Brain Behav."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/cns.13280","article-title":"Neuro-Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice","volume":"26","author":"Shafarevich","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1080\/21678421.2017.1407796","article-title":"Riluzole does not improve lifespan or motor function in three ALS mouse models","volume":"19","author":"Hogg","year":"2018","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1111\/j.1742-4658.2009.07057.x","article-title":"Proteomic characterization of lipid raft proteins in amyotrophic lateral sclerosis mouse spinal cord","volume":"276","author":"Zhai","year":"2009","journal-title":"FEBS J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fernandez-Beltran, L.C., Godoy-Corchuelo, J.M., Losa-Fontangordo, M., Williams, D., Matias-Guiu, J., and Corrochano, S. (2021). A Transcriptomic Meta-Analysis Shows Lipid Metabolism Dysregulation as an Early Pathological Mechanism in the Spinal Cord of SOD1 Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179553"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"883","DOI":"10.3389\/fphar.2019.00883","article-title":"Ambroxol Hydrochloride Improves Motor Functions and Extends Survival in a Mouse Model of Familial Amyotrophic Lateral Sclerosis","volume":"10","author":"Bouscary","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5389","DOI":"10.7150\/thno.72614","article-title":"Subpial delivery of adeno-associated virus 9-synapsin-caveolin-1 (AAV9-SynCav1) preserves motor neuron and neuromuscular junction morphology, motor function, delays disease onset, and extends survival in hSOD1(G93A) mice","volume":"12","author":"Wang","year":"2022","journal-title":"Theranostics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7545","DOI":"10.1096\/fj.201802652RR","article-title":"Neuron-targeted caveolin-1 improves neuromuscular function and extends survival in SOD1(G93A) mice","volume":"33","author":"Sawada","year":"2019","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"105205","DOI":"10.1016\/j.chemphyslip.2022.105205","article-title":"Influence of ceramide on lipid domain stability studied with small-angle neutron scattering: The role of acyl chain length and unsaturation","volume":"245","author":"DiPasquale","year":"2022","journal-title":"Chem. Phys. Lipids"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"121507","DOI":"10.1016\/j.lfs.2023.121507","article-title":"Sphingomyelinase modulates synaptic vesicle mobilization at the mice neuromuscular junctions","volume":"318","author":"Tsentsevitsky","year":"2023","journal-title":"Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Petrov, A.M., Shalagina, M.N., Protopopov, V.A., Sergeev, V.G., Ovechkin, S.V., Ovchinina, N.G., Sekunov, A.V., Zefirov, A.L., Zakirjanova, G.F., and Bryndina, I.G. (2019). Changes in Membrane Ceramide Pools in Rat Soleus Muscle in Response to Short-Term Disuse. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194860"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"121120","DOI":"10.1016\/j.lfs.2022.121120","article-title":"K(ATP) channels as ROS-dependent modulator of neurotransmitter release at the neuromuscular junctions","volume":"310","author":"Tsentsevitsky","year":"2022","journal-title":"Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.freeradbiomed.2020.05.017","article-title":"Cadmium desynchronizes neurotransmitter release in the neuromuscular junction: Key role of ROS","volume":"155","author":"Tsentsevitsky","year":"2020","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ijdevneu.2013.12.010","article-title":"Kinetics of neurotransmitter release in neuromuscular synapses of newborn and adult rats","volume":"34","author":"Khuzakhmetova","year":"2014","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_44","first-page":"49","article-title":"The statistics of transmitter release at chemical synapses","volume":"17","author":"McLachlan","year":"1978","journal-title":"Int. Rev. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109021","DOI":"10.1016\/j.neuropharm.2022.109021","article-title":"GIRK channel as a versatile regulator of neurotransmitter release via L-type Ca2+ channel-dependent mechanism in the neuromuscular junction","volume":"209","author":"Tsentsevitsky","year":"2022","journal-title":"Neuropharmacology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bukharaeva, E.A., Skorinkin, A.I., Samigullin, D.V., and Petrov, A.M. (2022). Presynaptic Acetylcholine Receptors Modulate the Time Course of Action Potential-Evoked Acetylcholine Quanta Secretion at Neuromuscular Junctions. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081771"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ginebaugh, S.P., Badawi, Y., Tarr, T.B., and Meriney, S.D. (2022). Neuromuscular Active Zone Structure and Function in Healthy and Lambert-Eaton Myasthenic Syndrome States. Biomolecules, 12.","DOI":"10.3390\/biom12060740"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.neuroscience.2019.04.011","article-title":"Calcium influx through muscle nAChR-channels: One route, multiple roles","volume":"439","author":"Grassi","year":"2020","journal-title":"Neuroscience"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.neuron.2017.02.047","article-title":"The Mechanisms and Functions of Synaptic Facilitation","volume":"94","author":"Jackman","year":"2017","journal-title":"Neuron"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1111\/joa.13526","article-title":"Maturation of a postsynaptic domain: Role of small Rho GTPases in organising nicotinic acetylcholine receptor aggregates at the vertebrate neuromuscular junction","volume":"241","author":"Henriquez","year":"2022","journal-title":"J. Anat."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"134434","DOI":"10.1016\/j.neulet.2019.134434","article-title":"Nicotinic acetylcholine receptor at vertebrate motor endplates: Endocytosis, recycling, and degradation","volume":"711","author":"Rudolf","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1002\/jcsm.12945","article-title":"Muscle cells of sporadic amyotrophic lateral sclerosis patients secrete neurotoxic vesicles","volume":"13","author":"Duddy","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Romagnoli, C., Sharma, P., Zonefrati, R., Palmini, G., Lucattelli, E., Ward, D.T., Ellinger, I., Innocenti, M., and Brandi, M.L. (2021). Study of the Expression and Function of Calcium-Sensing Receptor in Human Skeletal Muscle. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147282"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e202213128","DOI":"10.1085\/jgp.202213128","article-title":"Nerve-dependent distribution of subsynaptic type 1 inositol 1,4,5-trisphosphate receptor at the neuromuscular junction","volume":"154","author":"Volpe","year":"2022","journal-title":"J. Gen. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1038\/s41467-021-23188-8","article-title":"Synaptic FUS accumulation triggers early misregulation of synaptic RNAs in a mouse model of ALS","volume":"12","author":"Sahadevan","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.tins.2023.01.001","article-title":"Condensate biology of synaptic vesicle clusters","volume":"46","author":"Sansevrino","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"bio055129","DOI":"10.1242\/bio.055129","article-title":"Overexpression of an ALS-associated FUS mutation in C. elegans disrupts NMJ morphology and leads to defective neuromuscular transmission","volume":"9","author":"Markert","year":"2020","journal-title":"Biol. Open."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.celrep.2017.09.028","article-title":"Post-transcriptional Inhibition of Hsc70-4\/HSPA8 Expression Leads to Synaptic Vesicle Cycling Defects in Multiple Models of ALS","volume":"21","author":"Coyne","year":"2017","journal-title":"Cell. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6403","DOI":"10.1038\/s41598-019-42833-3","article-title":"SNAP-25 isoforms differentially regulate synaptic transmission and long-term synaptic plasticity at central synapses","volume":"9","author":"Irfan","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2011.10.035","article-title":"Presynaptic residual calcium and synaptic facilitation at hippocampal synapses of mice with altered expression of SNAP-25","volume":"1431","author":"Scullin","year":"2012","journal-title":"Brain Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1523\/JNEUROSCI.0844-16.2016","article-title":"Synapsin II Regulation of GABAergic Synaptic Transmission Is Dependent on Interneuron Subtype","volume":"37","author":"Feliciano","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zhang, M., and Augustine, G.J. (2021). Synapsins and the Synaptic Vesicle Reserve Pool: Floats or Anchors?. Cells, 10.","DOI":"10.3390\/cells10030658"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e47434","DOI":"10.7554\/eLife.47434","article-title":"The readily-releasable pool dynamically regulates multivesicular release","volume":"8","author":"Vaden","year":"2019","journal-title":"Elife"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"101676","DOI":"10.1016\/j.arr.2022.101676","article-title":"ATP-sensitive potassium channels: A double-edged sword in neurodegenerative diseases","volume":"80","author":"Lv","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13024-022-00591-3","article-title":"FUS-ALS hiPSC-derived astrocytes impair human motor units through both gain-of-toxicity and loss-of-support mechanisms","volume":"18","author":"Terrie","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"19590","DOI":"10.1523\/JNEUROSCI.3396-13.2013","article-title":"Defects in synapse structure and function precede motor neuron degeneration in Drosophila models of FUS-related ALS","volume":"33","author":"Shahidullah","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e1062","DOI":"10.1212\/WNL.0000000000201657","article-title":"Association between Serum Lipids and Survival in Patients with Amyotrophic Lateral Sclerosis: A Meta-analysis and Population-Based Study","volume":"100","author":"Hackeng","year":"2023","journal-title":"Neurology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s40035-022-00322-0","article-title":"Deciphering lipid dysregulation in ALS: From mechanisms to translational medicine","volume":"11","author":"Agrawal","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"ref_69","first-page":"524","article-title":"25-Hydroxycholesterol as a Signaling Molecule of the Nervous System","volume":"87","author":"Odnoshivkina","year":"2022","journal-title":"Biochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/ana.10312","article-title":"Evidence that accumulation of ceramides and cholesterol esters mediates oxidative stress-induced death of motor neurons in amyotrophic lateral sclerosis","volume":"52","author":"Cutler","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fnmol.2018.00012","article-title":"Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of Oxysterols and Phytosterols","volume":"11","author":"Vejux","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/s41598-020-80378-y","article-title":"Sterol auto-oxidation adversely affects human motor neuron viability and is a neuropathological feature of amyotrophic lateral sclerosis","volume":"11","author":"Dodge","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_73","first-page":"1166","article-title":"Changes in the Metabolism of Sphingoid Bases in the Brain and Spinal Cord of Transgenic FUS(1-359) Mice, a Model of Amyotrophic Lateral Sclerosis","volume":"84","author":"Gutner","year":"2019","journal-title":"Biochemistry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41418-022-01089-7","article-title":"SPY1 inhibits neuronal ferroptosis in amyotrophic lateral sclerosis by reducing lipid peroxidation through regulation of GCH1 and TFR1","volume":"30","author":"Wang","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.mcn.2018.03.006","article-title":"24S-hydroxycholesterol suppresses neuromuscular transmission in SOD1(G93A) mice: A possible role of NO and lipid rafts","volume":"88","author":"Mukhutdinova","year":"2018","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e1290","DOI":"10.1038\/cddis.2014.243","article-title":"Loss of function of the ALS protein SigR1 leads to ER pathology associated with defective autophagy and lipid raft disturbances","volume":"5","author":"Vollrath","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"C627","DOI":"10.1152\/ajpcell.00365.2016","article-title":"Membrane lipid rafts are disturbed in the response of rat skeletal muscle to short-term disuse","volume":"312","author":"Petrov","year":"2017","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2017.11.009","article-title":"Clomipramine counteracts lipid raft disturbance due to short-term muscle disuse","volume":"664","author":"Bryndina","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"621","DOI":"10.5483\/BMBRep.2022.55.12.142","article-title":"Acid sphingomyelinase inhibition improves motor behavioral deficits and neuronal loss in an amyotrophic lateral sclerosis mouse model","volume":"55","author":"Choi","year":"2022","journal-title":"BMB Rep."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Bryndina, I.G., Shalagina, M.N., Protopopov, V.A., Sekunov, A.V., Zefirov, A.L., Zakirjanova, G.F., and Petrov, A.M. (2021). Early Lipid Raft-Related Changes: Interplay between Unilateral Denervation and Hindlimb Suspension. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052239"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.bbalip.2016.04.010","article-title":"Similar oxysterols may lead to opposite effects on synaptic transmission: Olesoxime versus 5alpha-cholestan-3-one at the frog neuromuscular junction","volume":"1861","author":"Kasimov","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1002\/cne.24466","article-title":"Sphingolipids regulate neuromuscular synapse structure and function in Drosophila","volume":"526","author":"West","year":"2018","journal-title":"J. Comp. Neurol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.cbi.2008.03.020","article-title":"Role of lipid rafts in agrin-elicited acetylcholine receptor clustering","volume":"175","author":"Pato","year":"2008","journal-title":"Chem. Biol. Interact."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Krivoi, I.I., and Petrov, A.M. (2019). Cholesterol and the Safety Factor for Neuromuscular Transmission. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051046"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.bbrc.2005.01.111","article-title":"Synaptic proteins and SNARE complexes are localized in lipid rafts from rat brain synaptosomes","volume":"329","author":"Gil","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.neuroscience.2015.03.036","article-title":"Sphingomyelin derivatives increase the frequency of microvesicle and granule fusion in chromaffin cells","volume":"295","author":"Montes","year":"2015","journal-title":"Neuroscience"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1074\/mcp.M600161-MCP200","article-title":"Quantitative proteomics analysis of detergent-resistant membranes from chemical synapses: Evidence for cholesterol as spatial organizer of synaptic vesicle cycling","volume":"5","author":"Jia","year":"2006","journal-title":"Mol. Cell. Proteom."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/ejn.13552","article-title":"Synapsins regulate brain-derived neurotrophic factor-mediated synaptic potentiation and axon elongation by acting on membrane rafts","volume":"45","author":"Kao","year":"2017","journal-title":"Eur. J. Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1097\/NEN.0000000000000086","article-title":"Semaphorin 3A signaling through neuropilin-1 is an early trigger for distal axonopathy in the SOD1G93A mouse model of amyotrophic lateral sclerosis","volume":"73","author":"Venkova","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"105052","DOI":"10.1016\/j.nbd.2020.105052","article-title":"Muscle fiber-type specific terminal Schwann cell pathology leads to sprouting deficits following partial denervation in SOD1(G93A) mice","volume":"145","author":"Harrison","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"7759","DOI":"10.1523\/JNEUROSCI.1748-18.2020","article-title":"Properties of Glial Cell at the Neuromuscular Junction Are Incompatible with Synaptic Repair in the SOD1(G37R) ALS Mouse Model","volume":"40","author":"Martineau","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1112405","DOI":"10.3389\/fncel.2023.1112405","article-title":"Large-scale analyses of CAV1 and CAV2 suggest their expression is higher in post-mortem ALS brain tissue and affects survival","volume":"17","author":"Adey","year":"2023","journal-title":"Front. Cell. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1007\/s12035-020-02216-6","article-title":"Simvastatin Enhances Muscle Regeneration Through Autophagic Defect-Mediated Inflammation and mTOR Activation in G93ASOD1 Mice","volume":"58","author":"Wang","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"108730","DOI":"10.1016\/j.celrep.2021.108730","article-title":"Rare variant burden analysis within enhancers identifies CAV1 as an ALS risk gene","volume":"34","author":"Zhang","year":"2021","journal-title":"Cell. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1111\/j.1469-7793.1999.0879s.x","article-title":"Noradrenaline synchronizes evoked quantal release at frog neuromuscular junctions","volume":"517","author":"Bukcharaeva","year":"1999","journal-title":"J. Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.neuroscience.2018.12.027","article-title":"Action of Hydrogen Peroxide on Synaptic Transmission at the Mouse Neuromuscular Junction","volume":"399","author":"Giniatullin","year":"2019","journal-title":"Neuroscience"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1113\/jphysiol.1979.sp012784","article-title":"Voltage clamping of unparalysed cut rat diaphragm for study of transmitter release","volume":"290","author":"Glavinovic","year":"1979","journal-title":"J. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"245","DOI":"10.26907\/2542-064X.2019.2.245-254","article-title":"Elph: An Open-Source Program for Acquisition Control and Analysis of Electrophysiological Signals","volume":"161","author":"Zakharov","year":"2019","journal-title":"Uchenye Zap. Kazan. Univ. Seriya Estestv. Nauk."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11745-013-3845-8","article-title":"The beta-subunit of cholera toxin has a high affinity for ganglioside GM1 embedded into solid supported lipid membranes with a lipid raft-like composition","volume":"49","author":"Margheri","year":"2014","journal-title":"Lipids"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00418-008-0509-5","article-title":"Use of Bodipy-labeled sphingolipid and cholesterol analogs to examine membrane microdomains in cells","volume":"130","author":"Marks","year":"2008","journal-title":"Histochem. Cell. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"54","DOI":"10.32607\/20758251-2019-11-2-54-62","article-title":"Septin Polymerization Slows Synaptic Vesicle Recycling in Motor Nerve Endings","volume":"11","author":"Grigoryev","year":"2019","journal-title":"Acta Nat."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Zhilyakov, N., Arkhipov, A., Malomouzh, A., and Samigullin, D. (2021). Activation of Neuronal Nicotinic Receptors Inhibits Acetylcholine Release in the Neuromuscular Junction by Increasing Ca2+ Flux through Cav1 Channels. Int. J. Mol. Sci., 22.","DOI":"10.22541\/au.162321373.36083817\/v1"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/9022\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:38:51Z","timestamp":1760125131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/10\/9022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,19]]},"references-count":102,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24109022"],"URL":"https:\/\/doi.org\/10.3390\/ijms24109022","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,19]]}}}