{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T07:04:55Z","timestamp":1779433495125,"version":"3.53.1"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Synaptic Neurosci."],"abstract":"<jats:p>\n                    Motor neuron disease (MND) is marked by progressive neurodegeneration in which presynaptic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -handling and mitochondrial metabolism are thought to be vulnerable, but direct functional studies in human brain are scarce because most material is frozen long-term. Here, we show that synaptosomes isolated from paired fresh and experimentally frozen mouse cortex, and from cryopreserved human motor cortex, retain recognisable synaptosome ultrastructural features, synaptic proteome enrichment, and depolarisation-evoked Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -mobilisation. K\n                    <jats:sup>+<\/jats:sup>\n                    and veratridine elicited robust, pharmacologically suppressible Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx across preparations, and response amplitudes in human samples varied by region but did not correlate with donor age, post-mortem interval (PMI), or years in storage. Synaptosomes from neuropathologically confirmed MND motor cortex and hSOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    mouse cortex showed significantly greater depolarisation-evoked Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry than their respective controls, suggesting that increased presynaptic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx is shared across our human MND cohort and the hSOD1\n                    <jats:sup>G93A<\/jats:sup>\n                    mouse model. Using synaptosome preparations from MND and control motor cortices in Seahorse respiratory assays, we found that Complex IV-driven oxygen consumption (TMPD\/ascorbate\u2013evoked and azide-sensitive) was reduced in MND synaptosomes, whereas donor-matched free-mitochondrial fractions showed no group difference, supporting a Complex IV defect detectable in the synaptosome-enriched fraction within this cohort. By defining protein-to-OCR relationships for both fractions, we provide practical parameters for applying these assays to archived human cohorts. Together, these data suggest that archived cryopreserved human brain tissues can support informative synaptosome Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and bioenergetic readouts, and that synaptosome-enriched preparations may reveal disease-relevant presynaptic phenotypes in MND that are not evident in donor-matched bulk mitochondrial isolates.\n                  <\/jats:p>","DOI":"10.3389\/fnsyn.2026.1760254","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:08:14Z","timestamp":1779430094000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Synaptosomes isolated from cryopreserved MND motor cortex reveal altered calcium handling and reduced complex IV\u2013linked respiration"],"prefix":"10.3389","volume":"18","author":[{"given":"Sean D.","family":"Morrison","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland","place":["St Lucia, QLD, Australia"]},{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland","place":["St Lucia, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotten","family":"Ragnarsson","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland","place":["St Lucia, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah O.","family":"Cook","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland","place":["St Lucia, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Rothnagel","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland","place":["St Lucia, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst","family":"Wolvetang","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland","place":["St Lucia, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahaa","family":"Al-mhanawi","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland","place":["St Lucia, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed R.","family":"Shaker","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, The University of Queensland","place":["St Lucia, QLD, Australia"]},{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Education City","place":["Doha, Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Robertson","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland","place":["St Lucia, QLD, Australia"]},{"name":"Anatomical Pathology, Pathology Queensland","place":["Brisbane, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Dodd","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland","place":["St Lucia, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter G.","family":"Noakes","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland","place":["St Lucia, QLD, Australia"]},{"name":"Queensland Brain Institute, The University of Queensland","place":["St Lucia, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e104073","DOI":"10.15252\/embj.2019104073","article-title":"A novel approach to measure mitochondrial respiration in frozen biological samples","volume":"39","author":"Acin-Perez","year":"2020","journal-title":"EMBO J."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"100260","DOI":"10.1016\/j.crmeth.2022.100260","article-title":"An improved organotypic cell culture system to study tissue-resident macrophages ex vivo","volume":"2","author":"Aktories","year":"2022","journal-title":"Cell Rep. Methods"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1111\/j.1471-4159.1990.tb01946.x","article-title":"Stimulation of synaptosomal gamma-aminobutyric acid synthesis by glutamate and glutamine","volume":"54","author":"Battaglioli","year":"1990","journal-title":"J. Neurochem."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/s41593-021-01006-0","article-title":"Answer ALS, a large-scale resource for sporadic and familial ALS combining clinical and multi-omics data from induced pluripotent cell lines","volume":"25","author":"Baxi","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/embj.201386120","article-title":"Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting","volume":"33","author":"Biesemann","year":"2014","journal-title":"EMBO J."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e0151615","DOI":"10.1371\/journal.pone.0151615","article-title":"Individual case analysis of postmortem interval time on brain tissue preservation","volume":"11","author":"Blair","year":"2016","journal-title":"PLoS One"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"Biochem. J."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/ana.23937","article-title":"Stages of pTDP-43 pathology in amyotrophic lateral sclerosis","volume":"74","author":"Brettschneider","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.nbd.2006.01.001","article-title":"Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS","volume":"22","author":"Browne","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"7378","DOI":"10.1038\/s41598-022-09751-3","article-title":"Hyperexcitability in young iPSC-derived C9ORF72 mutant motor neurons is associated with increased intracellular calcium release","volume":"12","author":"Burley","year":"2022","journal-title":"Sci. Rep."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1096\/fj.201700835R","article-title":"Defects in synaptic transmission at the neuromuscular junction precede motor deficits in a TDP-43Q331K transgenic mouse model of amyotrophic lateral sclerosis","volume":"32","author":"Chand","year":"2018","journal-title":"FASEB J."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuint.2015.04.004","article-title":"SWATH analysis of the synaptic proteome in Alzheimer's disease","volume":"87","author":"Chang","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/s41593-025-01896-4","article-title":"Mitochondrial respiratory complex IV deficiency recapitulates amyotrophic lateral sclerosis","volume":"28","author":"Cheng","year":"2025","journal-title":"Nat. Neurosci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"4524","DOI":"10.1523\/JNEUROSCI.5817-10.2011","article-title":"Intrinsic bioenergetic properties and stress sensitivity of dopaminergic synaptosomes","volume":"31","author":"Choi","year":"2011","journal-title":"J. Neurosci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1111\/j.1471-4159.2009.06055.x","article-title":"Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: spare respiratory capacity and stochastic mitochondrial failure","volume":"109","author":"Choi","year":"2009","journal-title":"J. Neurochem."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1001\/archneurol.2010.128","article-title":"Mitochondrial respiratory chain dysfunction in muscle from patients with amyotrophic lateral sclerosis","volume":"67","author":"Crugnola","year":"2010","journal-title":"Arch. Neurol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/BF02834357","article-title":"Optimization of freezing, storage, and thawing conditions for the preparation of metabolically active synaptosomes from frozen rat and human brain","volume":"4","author":"Dodd","year":"1986","journal-title":"Neurochem. Pathol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/0006-8993(81)91086-6","article-title":"A rapid method for preparing synaptosomes: comparison, with alternative procedures","volume":"226","author":"Dodd","year":"1981","journal-title":"Brain Res."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1038\/nprot.2008.171","article-title":"A rapid percoll gradient procedure for preparation of synaptosomes","volume":"3","author":"Dunkley","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/978-1-4939-8739-9","article-title":"Synaptosome preparations: which procedure should I use?","volume":"141","author":"Dunkley","year":"2018","journal-title":"NeuroMethods"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"11159","DOI":"10.1073\/pnas.0402026101","article-title":"Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model","volume":"101","author":"Dupuis","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/S0022-3565(24)38752-X","article-title":"Drug interactions with the dopamine transporter in cryopreserved human caudate","volume":"296","author":"Eshleman","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1101\/pdb.top074450","article-title":"The synaptosome as a model system for studying synaptic physiology","volume":"2015","author":"Evans","year":"2015","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3627","DOI":"10.3390\/ijms23073627","article-title":"Synapses: the brain's energy-demanding sites","volume":"23","author":"Faria-Pereira","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"6868","DOI":"10.1021\/ac900881z","article-title":"Quantitative microplate-based respirometry with correction for oxygen diffusion","volume":"81","author":"Gerencser","year":"2009","journal-title":"Anal. Chem."},{"key":"ref9001","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/s0003-2697(02)00534-1","article-title":"In situ assay of the intramitochondrial enzymes: use of alamethicin for permeabilization of mitochondria","volume":"313","author":"Gostimskaya","year":"2002","journal-title":"Analytical Biochem."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.ceca.2009.12.002","article-title":"Calcium dysregulation in amyotrophic lateral sclerosis","volume":"47","author":"Grosskreutz","year":"2010","journal-title":"Cell Calcium"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1126\/science.8209258","article-title":"Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation","volume":"264","author":"Gurney","year":"1994","journal-title":"Science"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"eaau3644","DOI":"10.1126\/science.aau3644","article-title":"Local protein synthesis is a ubiquitous feature of neuronal pre- and postsynaptic compartments","volume":"364","author":"Hafner","year":"2019","journal-title":"Science"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1111\/j.1471-4159.1986.tb04523.x","article-title":"Uptake of gamma-aminobutyric acid and glycine by synaptosomes from postmortem human brain","volume":"47","author":"Hardy","year":"1986","journal-title":"J. Neurochem."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jns.2005.02.006","article-title":"Background and gender effects on survival in the TgN (SOD1-G93A) 1Gur mouse model of ALS","volume":"236","author":"Heiman-Patterson","year":"2005","journal-title":"J. Neurol. Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.4103\/1673-5374.382985","article-title":"Pathological mechanisms of amyotrophic lateral sclerosis","volume":"19","author":"Hu","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.tcb.2014.04.002","article-title":"NAD+ and sirtuins in aging and disease","volume":"24","author":"Imai","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1242\/dmm.024547","article-title":"Using the mouse to model human disease: increasing validity and reproducibility","volume":"9","author":"Justice","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1006\/exnr.1999.7190","article-title":"ALS-linked Cu\/Zn-SOD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanism involving increased oxidative stress and perturbed calcium homeostasis","volume":"160","author":"Kruman","year":"1999","journal-title":"Exp. Neurol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1177\/1073858406287661","article-title":"Mitochondria at the synapse","volume":"12","author":"Ly","year":"2006","journal-title":"Neuroscientist"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.nicl.2018.03.002","article-title":"Prefrontal cortical thickness in motor neuron disease","volume":"18","author":"Machts","year":"2018","journal-title":"Neuroimage Clin."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"4296","DOI":"10.1073\/pnas.1200658109","article-title":"Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis","volume":"109","author":"Marinkovic","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"29626","DOI":"10.1074\/jbc.M203065200","article-title":"Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice","volume":"277","author":"Mattiazzi","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.genm.2010.11.010","article-title":"Effects of gender in amyotrophic lateral sclerosis","volume":"7","author":"McCombe","year":"2010","journal-title":"Gend. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1016\/S0022-3565(24)35014-1","article-title":"Calcium channels involved in K+- and veratridine-induced increase of cytosolic calcium concentration in human cerebral cortical Synaptosomes1","volume":"290","author":"Meder","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"7189","DOI":"10.1074\/jbc.M116.774471","article-title":"Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements","volume":"292","author":"Mookerjee","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1111\/j.1471-4159.1984.tb12851.x","article-title":"Rapid preparation of synaptosomes from mammalian brain using nontoxic isoosmotic gradient material (Percoll)","volume":"43","author":"Nagy","year":"1984","journal-title":"J. Neurochem."},{"key":"ref43","volume-title":"Australian Code for the Care and Use of Animals for Scientific Purposes","year":"2013"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1152\/physrev.2000.80.1.315","article-title":"Mitochondria and neuronal survival","volume":"80","author":"Nicholls","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1038\/labinvest.2014.103","article-title":"Flow cytometry analysis of synaptosomes from post-mortem human brain reveals changes specific to lewy body and Alzheimer's disease","volume":"94","author":"Postupna","year":"2014","journal-title":"Lab. Investig."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/nrm3412","article-title":"Mitochondria as sensors and regulators of calcium signalling","volume":"13","author":"Rizzuto","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nrn3430","article-title":"The changing scene of amyotrophic lateral sclerosis","volume":"14","author":"Robberecht","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e21746","DOI":"10.1371\/journal.pone.0021746","article-title":"High throughput microplate respiratory measurements using minimal quantities of isolated mitochondria","volume":"6","author":"Rogers","year":"2011","journal-title":"PLoS One"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1111\/j.1471-4159.2006.03938.x","article-title":"Glycerotoxin stimulates neurotransmitter release from N-type Ca2+ channel expressing neurons","volume":"98","author":"Schenning","year":"2006","journal-title":"J. Neurochem."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/0304-3940(91)90653-b","article-title":"Evidence of glutamatergic deficiency in schizophrenia","volume":"121","author":"Sherman","year":"1991","journal-title":"Neurosci. Lett."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"132933","DOI":"10.1016\/j.neulet.2017.06.052","article-title":"The role of mitochondria in amyotrophic lateral sclerosis","volume":"710","author":"Smith","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"ENEURO.0369-0319.2020","DOI":"10.1523\/ENEURO.0369-19.2020","article-title":"Synaptic actions of amyotrophic lateral sclerosis-associated G85R-SOD1 in the squid giant synapse","volume":"7","author":"Song","year":"2020","journal-title":"eNeuro"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.stem.2015.05.004","article-title":"Programming and reprogramming cellular age in the era of induced pluripotency","volume":"16","author":"Studer","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s13578-020-00511-2","article-title":"CNS glucose metabolism in amyotrophic lateral sclerosis: a therapeutic target?","volume":"11","author":"Tefera","year":"2021","journal-title":"Cell Biosci."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/S0960-8966(03)00104-4","article-title":"Sexual differences in onset of disease and response to exercise in a transgenic model of ALS","volume":"13","author":"Veldink","year":"2003","journal-title":"Neuromuscul. Disord."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/978-94-007-2888-2_3","article-title":"Development and optimization of FLIPR high throughput calcium assays for ion channels and GPCRs","volume":"740","author":"Vetter","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1540","DOI":"10.1093\/brain\/awn071","article-title":"Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis","volume":"131","author":"Vucic","year":"2008","journal-title":"Brain"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.celrep.2014.03.019","article-title":"Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons","volume":"7","author":"Wainger","year":"2014","journal-title":"Cell Rep."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1212\/WNL.0000000000002135","article-title":"Brain morphologic changes in asymptomatic C9orf72 repeat expansion carriers","volume":"85","author":"Walhout","year":"2015","journal-title":"Neurology"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1038\/nm.4130","article-title":"The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity","volume":"22","author":"Wang","year":"2016","journal-title":"Nat. Med."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1042\/bj0900293","article-title":"The separation of synaptic vesicles from nerve-ending particles ('synaptosomes')","volume":"90","author":"Whittaker","year":"1964","journal-title":"Biochem. J."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3390\/cells14040276","article-title":"Mitochondrial dysfunction in neurodegenerative diseases","volume":"14","author":"Yang","year":"2025","journal-title":"Cells"}],"container-title":["Frontiers in Synaptic Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnsyn.2026.1760254\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:08:16Z","timestamp":1779430096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnsyn.2026.1760254\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":63,"alternative-id":["10.3389\/fnsyn.2026.1760254"],"URL":"https:\/\/doi.org\/10.3389\/fnsyn.2026.1760254","relation":{},"ISSN":["1663-3563"],"issn-type":[{"value":"1663-3563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]},"article-number":"1760254"}}