{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:42:00Z","timestamp":1792460520472,"version":"4.5.0"},"reference-count":188,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PSI2017-83893-R"],"award-info":[{"award-number":["PSI2017-83893-R"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00e0\u00ada, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["PSI2017-90806-REDT"],"award-info":[{"award-number":["PSI2017-90806-REDT"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disease caused by degeneration of motor neurons (MNs). ALS pathogenic features include accumulation of misfolded proteins, glutamate excitotoxicity, mitochondrial dysfunction at distal axon terminals, and neuronal cytoskeleton changes. Synergies between loss of C9orf72 functions and gain of function by toxic effects of repeat expansions also contribute to C9orf72-mediated pathogenesis. However, the impact of haploinsufficiency of C9orf72 on neurons and in synaptic functions requires further examination. As the motor neurons degenerate, the disease symptoms will lead to neurotransmission deficiencies in the brain, spinal cord, and neuromuscular junction. Altered neuronal excitability, synaptic morphological changes, and C9orf72 protein and DPR localization at the synapses, suggest a potential involvement of C9orf72 at synapses. In this review article, we provide a conceptual framework for assessing the putative involvement of C9orf72 as a synaptopathy, and we explore the underlying and common disease mechanisms with other neurodegenerative diseases. Finally, we reflect on the major challenges of understanding C9orf72-ALS as a synaptopathy focusing on integrating mitochondrial and neuronal cytoskeleton degeneration as biomarkers and potential targets to treat ALS neurodegeneration.<\/jats:p>","DOI":"10.3389\/fncel.2021.660693","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T05:24:53Z","timestamp":1622525093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Synaptopathy Mechanisms in ALS Caused by C9orf72 Repeat Expansion"],"prefix":"10.3389","volume":"15","author":[{"given":"Agnes L.","family":"Nishimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.stemcr.2020.01.010","article-title":"Knocking out C9ORF72 exacerbates axonal trafficking defects associated with hexanucleotide repeat expansion and reduces levels of heat shock proteins","volume":"14","author":"Abo-Rady","year":"2020","journal-title":"Stem Cell Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"203536","DOI":"10.1155\/2012\/203536","article-title":"Intracellular Ca2+ stores and Ca2+ influx are both required for BDNF to rapidly increase quantal vesicular transmitter release","volume":"2012","author":"Amaral","year":"2012","journal-title":"Neural Plast."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.expneurol.2011.12.013","article-title":"Protein aggregates in Huntington\u2019s disease","volume":"238","author":"Arrasate","year":"2012","journal-title":"Exp. Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.neuron.2013.02.004","article-title":"Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD\/ALS","volume":"77","author":"Ash","year":"2013","journal-title":"Neuron"},{"key":"B5","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s40478-015-0238-7","article-title":"C9ORF72 expression and cellular localization over mouse development","volume":"3","author":"Atkinson","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1097\/00004647-200110000-00001","article-title":"An energy budget for signaling in the grey matter of the brain","volume":"21","author":"Attwell","year":"2001","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2378","DOI":"10.1093\/hmg\/ddw105","article-title":"Axonal transport defects are a common phenotype in Drosophila models of ALS","volume":"25","author":"Baldwin","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/s41582-018-0047-2","article-title":"C9orf72-mediated ALS and FTD: multiple pathways to disease","volume":"14","author":"Balendra","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/00016489209137072","article-title":"The acoustic cortex in Alzheimer\u2019s disease","volume":"494","author":"Baloyannis","year":"1992","journal-title":"Acta Otolaryngol. Suppl."},{"key":"B10","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1080\/000164801300043884","article-title":"The acoustic cortex in frontal dementia","volume":"121","author":"Baloyannis","year":"2001","journal-title":"Acta Otolaryngol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1080\/21678421.2019.1646769","article-title":"Neurofilaments in pre-symptomatic ALS and the impact of genotype","volume":"20","author":"Benatar","year":"2019","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.2174\/1381612826666200113162641","article-title":"Excitotoxicity as a target against neurodegenerative processes","volume":"26","author":"Binvignat","year":"2020","journal-title":"Curr. Pharm. Des."},{"key":"B13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1750-1326-7-23","article-title":"Absence of amyloid beta oligomers at the postsynapse and regulated synaptic Zn2+ in cognitively intact aged individuals with Alzheimer\u2019s disease neuropathology","volume":"7","author":"Bjorklund","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"B14","doi-asserted-by":"publisher","first-page":"11043","DOI":"10.1523\/JNEUROSCI.1924-09.2009","article-title":"Neurofilaments bind tubulin and modulate its polymerization","volume":"29","author":"Bocquet","year":"2009","journal-title":"J. Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1038\/nn.2660","article-title":"Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS","volume":"13","author":"Bosco","year":"2010","journal-title":"Nat. Neurosci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/nrneurol.2013.221","article-title":"Amyotrophic lateral sclerosis\u2014a model of corticofugal axonal spread","volume":"9","author":"Braak","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/nrm3609","article-title":"Functions of cofilin in cell locomotion and invasion","volume":"14","author":"Bravo-Cordero","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s00401-014-1299-6","article-title":"TDP-43 pathology and neuronal loss in amyotrophic lateral sclerosis spinal cord","volume":"128","author":"Brettschneider","year":"2014","journal-title":"Acta Neuropathol."},{"key":"B19","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":"B20","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/0092-8674(92)90154-5","article-title":"Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG). repeat at the 3\u2032 end of a transcript encoding a protein kinase family member","volume":"68","author":"Brook","year":"1992","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1074\/jbc.M113.490862","article-title":"Collapsin response mediator protein 5 (CRMP5). induces mitophagy, thereby regulating mitochondrion numbers in dendrites","volume":"289","author":"Brot","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1002\/syn.890080205","article-title":"Organization of mitochondria in olfactory bulb granule cell dendritic spines","volume":"8","author":"Cameron","year":"1991","journal-title":"Synapse"},{"key":"B23","doi-asserted-by":"publisher","first-page":"972","DOI":"10.3390\/brainsci10120972","article-title":"The significance of tau aggregates in the human","volume":"10","author":"Castellani","year":"2020","journal-title":"Brain Sci."},{"key":"B24","first-page":"255","article-title":"Decreased numbers of dendritic spines on cortical pyramidal neurons in dementia. A quantitative Golgi study on biopsy samples","volume":"6","author":"Catala","year":"1988","journal-title":"Hum. Neurobiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e00045","DOI":"10.1042\/AN20100019","article-title":"Mitochondria and neuroplasticity","volume":"2","author":"Cheng","year":"2010","journal-title":"ASN Neuro"},{"key":"B25","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.jmb.2007.01.088","article-title":"Haploinsuffciency for Znf9 in Znf9+\/\u2013 mice is associated with multiorgan abnormalities resembling myotonic dystrophy","volume":"368","author":"Chen","year":"2007","journal-title":"J. Mol. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.ajpath.2012.10.027","article-title":"Mutant LRRK2 elicits calcium imbalance and depletion of dendritic mitochondria in neurons","volume":"182","author":"Cherra","year":"2013","journal-title":"Am. J. Pathol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/j.bbadis.2006.04.002","article-title":"Axonal transport and neurodegenerative disease","volume":"1762","author":"Chevalier-Larsen","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"B29","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1038\/s41593-019-0397-0","article-title":"C9ORF72-ALS\/FTD-associated poly (GR) binds Atp5a1 and compromises mitochondrial function in vivo","volume":"22","author":"Choi","year":"2019","journal-title":"Nat. Neurosci."},{"key":"B203","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1523\/JNEUROSCI.04-08-02080.1984","article-title":"Initial expression of neurofilaments and vimentin in the central and peripheral nervous system of the mouse embryo in vivo","volume":"4","author":"Cochard","year":"1984","journal-title":"J. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1212\/01.wnl.0000140626.48118.0a","article-title":"A focus on the synapse for neuroprotection in Alzheimer disease and other dementias","volume":"63","author":"Coleman","year":"2004","journal-title":"Neurology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"R677","DOI":"10.1016\/j.cub.2015.06.020","article-title":"Coordinating neuronal actin-microtubule dynamics","volume":"25","author":"Coles","year":"2015","journal-title":"Curr. Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"105246","DOI":"10.1016\/j.nbd.2020.105246","article-title":"Increased glutamate transmission onto dorsal striatum spiny projection neurons in Pink1 knockout rats","volume":"150","author":"Creed","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1016\/j.stemcr.2020.03.023","article-title":"Impairment of mitochondrial calcium buffering links mutations in C9ORF72 and TARDBP in iPS-derived motor neurons from patients with ALS\/FTD","volume":"14","author":"Dafinca","year":"2020","journal-title":"Stem Cell Reports"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1002\/stem.2388","article-title":"C9orf72 hexanucleotide expansions are associated with altered endoplasmic reticulum calcium homeostasis and stress granule formation in induced pluripotent stem cell-derived neurons from patients with amyotrophic lateral sclerosis and frontotemporal dementia","volume":"34","author":"Dafinca","year":"2016","journal-title":"Stem Cells"},{"key":"B37","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"key":"B38","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1002\/ana.410270502","article-title":"Synapse loss in frontal cortex biopsies in Alzheimer\u2019s disease: correlation with cognitive severity","volume":"27","author":"DeKosky","year":"1990","journal-title":"Ann. Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"5999","DOI":"10.1038\/ncomms6999","article-title":"Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability","volume":"6","author":"Devlin","year":"2015","journal-title":"Nat. Commun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/0006-8993(87)90028-x","article-title":"Morphometric and dendritic analysis of fascia dentata granule cells in human aging and senile dementia","volume":"402","author":"de Ruiter","year":"1987","journal-title":"Brain Res."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15214","article-title":"Mislocalisation of TDP-43 to the cytoplasm causes cortical hyperexcitability and reduced excitatory neurotransmission in the motor cortex","author":"Dyer","year":"2020","journal-title":"J. Neurochem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1523\/JNEUROSCI.18-02-00720.1998","article-title":"Splice variant-specific interaction of the NMDA receptor subunit NR1 with neuronal intermediate filaments","volume":"18","author":"Ehlers","year":"1998","journal-title":"J. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"5077","DOI":"10.1523\/JNEUROSCI.14-08-05077.1994","article-title":"Dendritic pathology of granule cells in Alzheimer\u2019s disease is unrelated to neuritic plaques","volume":"14","author":"Einstein","year":"1994","journal-title":"J. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"19606","DOI":"10.1038\/s41598-020-76456-w","article-title":"Changes in neuronal excitability and synaptic transmission in nucleus accumbens in a transgenic Alzheimer\u2019s disease mouse model","volume":"10","author":"Fernandez-Perez","year":"2020","journal-title":"Sci. Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3877","DOI":"10.1523\/JNEUROSCI.11-12-03877.1991","article-title":"Proliferative and degenerative changes in striatal spiny neurons in Huntington\u2019s disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry","volume":"11","author":"Ferrante","year":"1991","journal-title":"J. Neurosci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1159\/000051214","article-title":"Neurons and their dendrites in frontotemporal dementia","volume":"10","author":"Ferrer","year":"1999","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"B46","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1007\/BF00294247","article-title":"Down\u2019s syndrome and Alzheimer\u2019s disease: dendritic spine counts in the hippocampus","volume":"79","author":"Ferrer","year":"1990","journal-title":"Acta Neuropathol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1136\/jnnp.54.10.932","article-title":"Dementia of frontal lobe type and motor neuron disease. A Golgi study of the frontal cortex","volume":"54","author":"Ferrer","year":"1991","journal-title":"J. Neurol. Neurosurg. Psychiatry."},{"key":"B48","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1136\/jnnp.54.10.932","article-title":"Driven to decay: excitability and synaptic abnormalities in amyotrophic lateral sclerosis","volume":"140","author":"Fogarty","year":"2018","journal-title":"Brain Res. Bull."},{"key":"B49","doi-asserted-by":"publisher","first-page":"189","DOI":"10.4103\/1673-5374.244782","article-title":"Amyotrophic lateral sclerosis as a synaptopathy","volume":"14","author":"Fogarty","year":"2019","journal-title":"Neural Regen. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"609","DOI":"10.3389\/fnins.2017.00609","article-title":"Motor areas show altered dendritic structure in an amyotrophic lateral sclerosis mouse model","volume":"11","author":"Fogarty","year":"2017","journal-title":"Front. Neurosci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/nature14974","article-title":"GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport","volume":"525","author":"Freibaum","year":"2015","journal-title":"Nature"},{"key":"B52","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s40478-018-0579-0","article-title":"Novel antibodies reveal presynaptic localization of C9orf72 protein and reduced protein levels in C9orf72 mutation carriers","volume":"6","author":"Frick","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"B53","doi-asserted-by":"publisher","first-page":"eabg3013","DOI":"10.1126\/sciadv.abg3013","article-title":"C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility","volume":"7","author":"Fumagalli","year":"2021","journal-title":"Sci. Adv."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1093\/brain\/awaa098","article-title":"Neurofilaments: neurobiological foundations for biomarker applications","volume":"143","author":"Gafson","year":"2020","journal-title":"Brain"},{"key":"B55","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/373523a0","article-title":"Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein","volume":"373","author":"Games","year":"1995","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","first-page":"41765","DOI":"10.1038\/srep41765","article-title":"Apical dendrite degeneration, a novel cellular pathology for Betz cells in ALS","volume":"7","author":"Genc","year":"2017","journal-title":"Sci. Rep."},{"key":"B57","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1002\/ana.24980","article-title":"Phosphorylated neurofilament heavy chain: a biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis","volume":"82","author":"Gendron","year":"2017","journal-title":"Ann. Neurol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1007\/s00441-014-2082-7","article-title":"Neurofilament dynamics and involvement in neurological disorders","volume":"360","author":"Gentil","year":"2015","journal-title":"Cell Tissue Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1523\/JNEUROSCI.0876-20.2020","article-title":"Implications of oligomeric amyloid-beta (oA\u03b242). signaling through alpha7beta2-nicotinic acetylcholine receptors (nAChR) on basal forebrain cholinergic neuronal intrinsic excitability and cognitive decline","volume":"41","author":"George","year":"2020","journal-title":"J. Neurosci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/0304-3940(87)90720-8","article-title":"The septo-hippocampal pathway in patients suffering from senile dementia of Alzheimer\u2019s type. Evidence for neuronal plasticity?","volume":"76","author":"Gertz","year":"1987","journal-title":"Neurosci. Lett."},{"key":"B61","doi-asserted-by":"publisher","first-page":"3827","DOI":"10.1038\/s41467-019-11837-y","article-title":"Modulation of actin polymerization affects nucleocytoplasmic transport in multiple forms of amyotrophic lateral sclerosis","volume":"10","author":"Giampetruzzi","year":"2019","journal-title":"Nat. Commun."},{"key":"B62","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3389\/fnmol.2016.00004","article-title":"The ubiquitin-proteasome system: potential therapeutic targets for Alzheimer\u2019s disease and spinal cord injury","volume":"9","author":"Gong","year":"2016","journal-title":"Front. Mol. Neurosci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1126\/science.3155875","article-title":"Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington\u2019s disease","volume":"227","author":"Graveland","year":"1985","journal-title":"Science"},{"key":"B64","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1006\/exnr.2000.7626","article-title":"Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production","volume":"169","author":"Guidetti","year":"2001","journal-title":"Exp. Neurol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nrn.2016.38","article-title":"The expanding biology of the C9orf72 nucleotide repeat expansion in neurodegenerative disease","volume":"17","author":"Haeusler","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1046\/j.1471-4159.2000.0750373.x","article-title":"Site-specific phosphorylation of neurofilament-L is mediated by calcium\/calmodulin-dependent protein kinase II in the apical dendrites during long-term potentiation","volume":"75","author":"Hashimoto","year":"2000","journal-title":"J. Neurochem."},{"key":"B67","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1177\/1073858417705059","article-title":"The actin cytoskeleton in SMA and ALS: how does it contribute to motoneuron degeneration?","volume":"24","author":"Hensel","year":"2018","journal-title":"Neuroscientist"},{"key":"B68","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1093\/brain\/aws367","article-title":"Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour","volume":"136","author":"Hernandez-Hernandez","year":"2013","journal-title":"Brain"},{"key":"B69","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1242\/dmm.029892","article-title":"Viral delivery of C9orf72 hexanucleotide repeat expansions in mice leads to repeat-length-dependent neuropathology and behavioural deficits","volume":"10","author":"Herranz-Martin","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"B70","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s40478-020-01030-4","article-title":"Deregulated expression of a longevity gene, Klotho, in the C9orf72 deletion mice with impaired synaptic plasticity and adult hippocampal neurogenesis","volume":"8","author":"Ho","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"B71","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.neuint.2004.03.007","article-title":"Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer\u2019s disease","volume":"45","author":"Hynd","year":"2004","journal-title":"Neurochem. Int."},{"key":"B72","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s12031-012-9848-8","article-title":"Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume","volume":"49","author":"Ivannikov","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"E4016","DOI":"10.1073\/pnas.1309143110","article-title":"Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model","volume":"110","author":"Janezic","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"B74","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/ng0796-316","article-title":"Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice","volume":"13","author":"Jansen","year":"1996","journal-title":"Nat. Genet."},{"key":"B75","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.nbd.2012.03.036","article-title":"AAV2 mediated retrograde transduction of corticospinal motor neurons reveals initial and selective apical dendrite degeneration in ALS","volume":"47","author":"Jara","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"B76","doi-asserted-by":"publisher","first-page":"e10722","DOI":"10.15252\/emmm.201910722","article-title":"Synaptic dysfunction induced by glycine-alanine dipeptides in C9orf72-ALS\/FTD is rescued by SV2 replenishment","volume":"12","author":"Jensen","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"B77","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.neuron.2016.04.006","article-title":"Gain of toxicity from ALS\/FTD-linked repeat expansions in C9ORF72 is alleviated by antisense oligonucleotides targeting GGGGCC-containing RNAs","volume":"90","author":"Jiang","year":"2016","journal-title":"Neuron"},{"key":"B78","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1016\/j.ajpath.2011.07.013","article-title":"RNA Foci, CUGBP1 and ZNF9 are the primary targets of the mutant CUG and CCUG repeats expanded in myotonic dystrophies type 1 and type 2","volume":"179","author":"Jones","year":"2011","journal-title":"Am. J. Pathol."},{"key":"B201","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/0197-4580(94)00169-2","article-title":"Mice overexpressing the human neurofilament heavy gene as a model of ALS","volume":"16","author":"Julien","year":"1995","journal-title":"Neurobiol. Aging."},{"key":"B79","doi-asserted-by":"publisher","first-page":"6856","DOI":"10.1007\/s12035-019-1550-1","article-title":"Overview of impaired BDNF signaling, their coupled downstream serine-threonine kinases and SNARE\/SM complex in the neuromuscular junction of the amyotrophic lateral sclerosis model SOD1\u2013G93A mice","volume":"56","author":"Just-Borras","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.bbadis.2006.06.006","article-title":"Failure of protein quality control in amyotrophic lateral sclerosis","volume":"1762","author":"Kabashi","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"B81","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41582-018-0058-z","article-title":"Neurofilaments as biomarkers in neurological disorders","volume":"14","author":"Khalil","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.expneurol.2015.09.019","article-title":"Excitotoxicity in ALS: overstimulation, or overreaction?","volume":"275","author":"King","year":"2016","journal-title":"Exp. Neurol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"R471","DOI":"10.1016\/j.cub.2018.02.010","article-title":"Rab GTPases and membrane trafficking in neurodegeneration","volume":"28","author":"Kiral","year":"2018","journal-title":"Curr. Biol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"2667","DOI":"10.1152\/jn.2001.86.6.2667","article-title":"Electrophysiological and morphological changes in striatal spiny neurons in R6\/2 Huntington\u2019s disease transgenic mice","volume":"86","author":"Klapstein","year":"2001","journal-title":"J. Neurophysiol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1007\/s00401-001-0477-5","article-title":"Neuron loss from the hippocampus of Alzheimer\u2019s disease exceeds extracellular neurofibrillary tangle formation","volume":"103","author":"Kril","year":"2002","journal-title":"Acta Neuropathol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"4765","DOI":"10.1093\/hmg\/ddx350","article-title":"C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicity","volume":"26","author":"Lee","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"B86","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/0896-6273(94)90263-1","article-title":"A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease","volume":"13","author":"Lee","year":"1994","journal-title":"Neuron"},{"key":"B88","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1111\/jnc.13713","article-title":"Synaptopathies: synaptic dysfunction in neurological disorders - a review from students to students","volume":"138","author":"Lepeta","year":"2016","journal-title":"J. Neurochem."},{"key":"B89","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/bioinformatics\/bts725","article-title":"The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs","volume":"29","author":"Levine","year":"2013","journal-title":"Bioinformatics"},{"key":"B90","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.cell.2004.11.003","article-title":"The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses","volume":"119","author":"Li","year":"2004","journal-title":"Cell"},{"key":"B91","doi-asserted-by":"publisher","first-page":"3940","DOI":"10.1093\/hmg\/ddz230","article-title":"Smcr8 deficiency disrupts axonal transport-dependent lysosomal function and promotes axonal swellings and gain of toxicity in C9ALS\/FTD mouse models","volume":"28","author":"Liang","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"B92","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1242\/dmm.030049","article-title":"Early VGLUT1-specific parallel fiber synaptic deficits and dysregulated cerebellar circuit in the KIKO mouse model of Friedreich ataxia","volume":"10","author":"Lin","year":"2017","journal-title":"Dis. Model. Mech."},{"key":"B93","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1093\/hmg\/ddl132","article-title":"Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy","volume":"15","author":"Lin","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"B94","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/nature11557","article-title":"Progressive degeneration of human neural stem cells caused by pathogenic LRRK2","volume":"491","author":"Liu","year":"2012","journal-title":"Nature"},{"key":"B95","doi-asserted-by":"publisher","first-page":"816.e7","DOI":"10.1016\/j.neuron.2018.09.044","article-title":"ALS\/FTD-linked mutation in FUS suppresses intra-axonal protein synthesis and drives disease without nuclear loss-of-function of FUS","volume":"100","author":"Lopez-Erauskin","year":"2018","journal-title":"Neuron"},{"key":"B96","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.neuron.2016.09.015","article-title":"Poly(GR) in C9ORF72-related ALS\/FTD compromises mitochondrial function and increases oxidative stress and DNA damage in iPSC-derived motor neurons","volume":"92","author":"Lopez-Gonzalez","year":"2016","journal-title":"Neuron"},{"key":"B202","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1136\/jnnp-2014-307672","article-title":"Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study","volume":"86","author":"Lu","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B97","doi-asserted-by":"publisher","first-page":"a009357","DOI":"10.1101\/cshperspect.a009357","article-title":"The role of autophagy in Parkinson\u2019s disease","volume":"2","author":"Lynch-Day","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1093\/hmg\/ddt528","article-title":"Abnormal mitochondrial transport and morphology are common pathological denominators in SOD1 and TDP43 ALS mouse models","volume":"23","author":"Magrane","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B99","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.neuron.2004.09.012","article-title":"LTP and LTD: an embarrassment of riches","volume":"44","author":"Malenka","year":"2004","journal-title":"Neuron"},{"key":"B100","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1126\/science.285.5435.1870","article-title":"Long-term potentiation\u2013a decade of progress?","volume":"285","author":"Malenka","year":"1999","journal-title":"Science"},{"key":"B101","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3233\/JAD-130761","article-title":"Reduced VDAC1 protects against Alzheimer\u2019s disease, mitochondria and synaptic deficiencies","volume":"37","author":"Manczak","year":"2013","journal-title":"J Alzheimers Dis."},{"key":"B102","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/0896-6273(94)90264-x","article-title":"Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer\u2019s disease paired helical filament tau","volume":"13","author":"Matsuo","year":"1994","journal-title":"Neuron"},{"key":"B103","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1007\/s11064-006-9170-3","article-title":"Mitochondrial regulation of neuronal plasticity","volume":"32","author":"Mattson","year":"2007","journal-title":"Neurochem. Res."},{"key":"B104","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.neuron.2008.10.010","article-title":"Mitochondria in neuroplasticity and neurological disorders","volume":"60","author":"Mattson","year":"2008","journal-title":"Neuron"},{"key":"B105","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/s0006-291x(03)00627-2","article-title":"Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death","volume":"304","author":"Mattson","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B106","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1046\/j.1471-4159.1995.65041740.x","article-title":"Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2+ concentration and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons","volume":"65","author":"Mattson","year":"1995","journal-title":"J. Neurochem."},{"key":"B107","doi-asserted-by":"publisher","first-page":"6480","DOI":"10.1007\/s12035-017-0856-0","article-title":"Causative genes in amyotrophic lateral sclerosis and protein degradation pathways: a link to neurodegeneration","volume":"55","author":"Maurel","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1038\/sj.cdd.4400764","article-title":"Neurodegeneration: diseases of the cytoskeleton?","volume":"7","author":"McMurray","year":"2000","journal-title":"Cell Death Differ."},{"key":"B109","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/0006-8993(88)90124-2","article-title":"Atrophy of medium spiny I striatal dendrites in advanced Parkinson\u2019s disease","volume":"455","author":"McNeill","year":"1988","journal-title":"Brain Res."},{"key":"B110","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s00401-020-02252-5","article-title":"Mitochondrial bioenergetic deficits in C9orf72 amyotrophic lateral sclerosis motor neurons cause dysfunctional axonal homeostasis","volume":"141","author":"Mehta","year":"2021","journal-title":"Acta Neuropathol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.bbadis.2014.05.019","article-title":"Myotonic dystrophies: an update on clinical aspects, genetic, pathology and molecular pathomechanisms","volume":"1852","author":"Meola","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"B112","doi-asserted-by":"publisher","first-page":"4439","DOI":"10.1093\/emboj\/19.17.4439","article-title":"Recruitment of human muscleblind proteins to (CUG)(n). expansions associated with myotonic dystrophy","volume":"19","author":"Miller","year":"2000","journal-title":"EMBO J."},{"key":"B113","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1126\/science.1256800","article-title":"C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins","volume":"345","author":"Mizielinska","year":"2014","journal-title":"Science"},{"key":"B114","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1126\/science.1232927","article-title":"The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD\/ALS","volume":"339","author":"Mori","year":"2013","journal-title":"Science"},{"key":"B115","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1046\/j.1365-2443.1996.05005.x","article-title":"Phosphorylation of Ser-3 of cofilin regulates its essential function on actin","volume":"1","author":"Moriyama","year":"1996","journal-title":"Genes Cells"},{"key":"B116","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1242\/jcs.104.3.917","article-title":"The regulation of bidirectional mitochondrial transport is coordinated with axonal outgrowth","volume":"104","author":"Morris","year":"1993","journal-title":"J. Cell Sci."},{"key":"B117","doi-asserted-by":"publisher","first-page":"4050","DOI":"10.1523\/JNEUROSCI.20-11-04050.2000","article-title":"High-level neuronal expression of abeta 1\u201342 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation","volume":"20","author":"Mucke","year":"2000","journal-title":"J. Neurosci."},{"key":"B118","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.semcdb.2011.08.007","article-title":"Neuronal polarization and the cytoskeleton","volume":"22","author":"Neukirchen","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"B120","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.semcdb.2011.08.007","article-title":"Repeat-associated non-ATG translation: molecular mechanisms and contribution to neurological disease","volume":"42","author":"Nguyen","year":"2019","journal-title":"Annu. Rev. Neurosci."},{"key":"B122","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/j.1582-4934.2008.00276.x","article-title":"The ubiquitin-proteasome system in Alzheimer\u2019s disease","volume":"12","author":"Oddo","year":"2008","journal-title":"J. Cell Mol. Med."},{"key":"B123","doi-asserted-by":"publisher","first-page":"9122","DOI":"10.1038\/s41598-019-45530-3","article-title":"Augmentation of spinal cord glutamatergic synaptic currents in zebrafish primary motoneurons expressing mutant human TARDBP (TDP-43)","volume":"9","author":"Petel Legare","year":"2019","journal-title":"Sci. Rep."},{"key":"B124","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1126\/science.280.5364.737","article-title":"Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy","volume":"280","author":"Philips","year":"1998","journal-title":"Science"},{"key":"B125","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S1474-4422(11)70015-1","article-title":"Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease","volume":"10","author":"Philips","year":"2011","journal-title":"Lancet Neurol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.neuron.2014.12.007","article-title":"The roles of PINK1, parkin and mitochondrial fidelity in Parkinson\u2019s disease","volume":"85","author":"Pickrell","year":"2015","journal-title":"Neuron"},{"key":"B127","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/nature01598","article-title":"The cytoskeleton, cellular motility and the reductionist agenda","volume":"422","author":"Pollard","year":"2003","journal-title":"Nature"},{"key":"B128","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1002\/cne.20682","article-title":"Mitochondria form a filamentous reticular network in hippocampal dendrites but are present as discrete bodies in axons: a three-dimensional ultrastructural study","volume":"492","author":"Popov","year":"2005","journal-title":"J. Comp. Neurol."},{"key":"B129","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1074\/mcp.RA119.001888","article-title":"Arginine in C9ORF72 dipolypeptides mediates promiscuous proteome binding and multiple modes of toxicity","volume":"19","author":"Radwan","year":"2020","journal-title":"Mol. Cell. Proteomics"},{"key":"B130","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1111\/j.1471-4159.2004.02936.x","article-title":"Neurofilament-light increases the cell surface expression of the N-methyl-D-aspartate receptor and prevents its ubiquitination","volume":"92","author":"Ratnam","year":"2005","journal-title":"J. Neurochem."},{"key":"B131","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.stem.2013.01.008","article-title":"Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression","volume":"12","author":"Reinhardt","year":"2013","journal-title":"Cell Stem Cell"},{"key":"B132","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD","volume":"72","author":"Renton","year":"2011","journal-title":"Neuron"},{"key":"B133","doi-asserted-by":"publisher","first-page":"3092","DOI":"10.1111\/j.1460-9568.2004.03783.x","article-title":"Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington\u2019s disease mutation","volume":"20","author":"Ribchester","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"B134","doi-asserted-by":"publisher","first-page":"4337","DOI":"10.1523\/JNEUROSCI.19-11-04337.1999","article-title":"The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus","volume":"19","author":"Roberson","year":"1999","journal-title":"J. Neurosci."},{"key":"B135","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1093\/brain\/awu057","article-title":"Accumulation of oligomer-prone alpha-synuclein exacerbates synaptic and neuronal degeneration in vivo","volume":"137","author":"Rockenstein","year":"2014","journal-title":"Brain"},{"key":"B136","doi-asserted-by":"publisher","first-page":"104515","DOI":"10.1016\/j.nbd.2019.104515","article-title":"New pathologic mechanisms in nucleotide repeat expansion disorders","volume":"130","author":"Rodriguez","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"B137","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.ncl.2015.07.012","article-title":"Neuropathology of amyotrophic lateral sclerosis and its variants","volume":"33","author":"Saberi","year":"2015","journal-title":"Neurol. Clin."},{"key":"B138","doi-asserted-by":"publisher","first-page":"208ra149","DOI":"10.1126\/scitranslmed.3007529","article-title":"Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion","volume":"5","author":"Sareen","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"B139","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0197-4580(90)90059-9","article-title":"Quantitative assessment of cortical synaptic density in Alzheimer\u2019s disease","volume":"11","author":"Scheff","year":"1990","journal-title":"Neurobiol. Aging"},{"key":"B140","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1002\/ana.410330209","article-title":"Synapse loss in the temporal lobe in Alzheimer\u2019s disease","volume":"33","author":"Scheff","year":"1993","journal-title":"Ann. Neurol."},{"key":"B141","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.neurobiolaging.2003.08.002","article-title":"Synaptic pathology in Alzheimer\u2019s disease: a review of ultrastructural studies","volume":"24","author":"Scheff","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"B142","first-page":"107","article-title":"Dendritic changes in senile and presenile dementias","volume":"57","author":"Scheibel","year":"","journal-title":"Res. Publ. Assoc. Res. Nerv. Ment. Dis."},{"key":"B143","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/0047-6374(79)90123-4","article-title":"The hippocampus: organizational patterns in health and senescence","volume":"9","author":"Scheibel","year":"","journal-title":"Mech. Ageing Dev."},{"key":"B144","doi-asserted-by":"publisher","first-page":"2721","DOI":"10.1111\/j.1460-9568.2005.04109.x","article-title":"Oxygen consumption and mitochondrial membrane potential indicate developmental adaptation in energy metabolism of rat cortical neurons","volume":"21","author":"Schuchmann","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"B145","doi-asserted-by":"publisher","first-page":"26364","DOI":"10.1074\/jbc.270.44.26364","article-title":"Deletion of 3\u2032-untranslated region alters the level of mRNA expression of a neurofilament light subunit transgene","volume":"270","author":"Schwartz","year":"1995","journal-title":"J. Biol. Chem."},{"key":"B146","doi-asserted-by":"publisher","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":"B147","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.15252\/embj.201593350","article-title":"Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death","volume":"35","author":"Sellier","year":"2016","journal-title":"EMBO J."},{"key":"B148","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/s41467-017-02729-0","article-title":"C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca(2+)-permeable AMPA receptor-mediated excitotoxicity","volume":"9","author":"Selvaraj","year":"2018","journal-title":"Nat. Commun."},{"key":"B149","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nm.4490","article-title":"Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS\/FTD human induced motor neurons","volume":"24","author":"Shi","year":"2018","journal-title":"Nat. Med."},{"key":"B150","doi-asserted-by":"publisher","first-page":"6292","DOI":"10.1523\/JNEUROSCI.21-16-06292.2001","article-title":"Sex differences and opposite effects of stress on dendritic spine density in the male versus female hippocampus","volume":"21","author":"Shors","year":"2001","journal-title":"J. Neurosci."},{"key":"B151","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1023\/a:1005552126516","article-title":"The local control of cytosolic Ca2+ as a propagator of CNS communication\u2014integration of mitochondrial transport mechanisms and cellular responses","volume":"32","author":"Simpson","year":"2000","journal-title":"J. Bioenerg. Biomembr."},{"key":"B152","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1038\/nn.4407","article-title":"C9ORF72 interaction with cofilin modulates actin dynamics in motor neurons","volume":"19","author":"Sivadasan","year":"2016","journal-title":"Nat. Neurosci."},{"key":"B153","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1038\/s41582-019-0257-2","article-title":"Axonal transport and neurological disease","volume":"15","author":"Sleigh","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"B154","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1523\/JNEUROSCI.17-01-00190.1997","article-title":"Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat","volume":"17","author":"Spacek","year":"1997","journal-title":"J. Neurosci."},{"key":"B155","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"B156","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/0006-8993(86)90130-7","article-title":"Hippocampal long-term potentiation increases mitochondrial calcium pump activity in rat","volume":"382","author":"Stanton","year":"1986","journal-title":"Brain Res."},{"key":"B157","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1111\/j.1469-7793.1997.501bd.x","article-title":"Kinetic analysis of the phosphorylation-dependent interactions of synapsin I with rat brain synaptic vesicles","volume":"504","author":"Stefani","year":"1997","journal-title":"J Physiol."},{"key":"B158","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1074\/jbc.M113.526129","article-title":"Brain-derived neurotrophic factor (BDNF)-induced mitochondrial motility arrest and presynaptic docking contribute to BDNF-enhanced synaptic transmission","volume":"289","author":"Su","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B159","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s40478-016-0324-5","article-title":"The ALS\/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway","volume":"4","author":"Sullivan","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"B160","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.3233\/JAD-170585","article-title":"Mitochondria and mitochondrial cascades in Alzheimer\u2019s disease","volume":"62","author":"Swerdlow","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"B161","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1002\/ana.410300410","article-title":"Physical basis of cognitive alterations in Alzheimer\u2019s disease: synapse loss is the major correlate of cognitive impairment","volume":"30","author":"Terry","year":"1991","journal-title":"Ann. Neurol."},{"key":"B162","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1074\/jbc.275.4.2439","article-title":"Neurofilament-L is a protein phosphatase-1-binding protein associated with neuronal plasma membrane and post-synaptic density","volume":"275","author":"Terry-Lorenzo","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B163","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1111\/ejn.14742","article-title":"What\u2019s wrong with the striatal cholinergic interneurons in Parkinson\u2019s disease? Focus on intrinsic excitability","volume":"53","author":"Tubert","year":"2020","journal-title":"Eur. J. Neurosci."},{"key":"B164","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.neubiorev.2014.01.012","article-title":"Mitochondrial dysfunction as a central actor in intellectual disability-related diseases: an overview of down syndrome, autism, fragile X and rett syndrome","volume":"46","author":"Valenti","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B165","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1126\/science.1165942","article-title":"Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6","volume":"323","author":"Vance","year":"2009","journal-title":"Science"},{"key":"B166","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.tins.2014.05.006","article-title":"Advances in treating amyotrophic lateral sclerosis: insights from pathophysiological studies","volume":"37","author":"Vucic","year":"2014","journal-title":"Trends Neurosci."},{"key":"B168","doi-asserted-by":"publisher","first-page":"4706","DOI":"10.1093\/hmg\/ddt319","article-title":"The ALS disease-associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons","volume":"22","author":"Wang","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"B167","doi-asserted-by":"publisher","first-page":"585584","DOI":"10.3389\/fnins.2020.585584","article-title":"Molecular mechanisms of glutamate toxicity in Parkinson\u2019s disease","volume":"14","author":"Wang","year":"","journal-title":"Front. Neurosci."},{"key":"B169","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13024-020-00376-6","article-title":"Mitochondria dysfunction in the pathogenesis of Alzheimer\u2019s disease: recent advances","volume":"15","author":"Wang","year":"","journal-title":"Mol. Neurodegener."},{"key":"B170","doi-asserted-by":"publisher","first-page":"e9423","DOI":"10.15252\/emmm.201809423","article-title":"Repeat-associated non-AUG translation in C9orf72-ALS\/FTD is driven by neuronal excitation and stress","volume":"11","author":"Westergard","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"B171","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/0006-8993(82)90456-5","article-title":"Changes in the hippocampal slices energy metabolism following stimulation and long-term potentiation of Schaffer collaterals-pyramidal cell synapses tested with the 2-deoxyglucose technique","volume":"237","author":"Wieraszko","year":"1982","journal-title":"Brain Res."},{"key":"B173","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/4553","article-title":"Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons","volume":"2","author":"Williamson","year":"1999","journal-title":"Nat. Neurosci."},{"key":"B172","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/s0169-328x(98)00165-x","article-title":"Synaptic activity-dependent modulation of mitochondrial gene expression in the rat hippocampus","volume":"60","author":"Williams","year":"1998","journal-title":"Mol. Brain Res."},{"key":"B174","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1097\/01.jnen.0000228202.35163.c4","article-title":"Synaptic vulnerability in neurodegenerative disease","volume":"65","author":"Wishart","year":"2006","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B175","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s00401-014-1253-7","article-title":"The C9ORF72 expansion mutation: gene structure, phenotypic and diagnostic issues","volume":"127","author":"Woollacott","year":"2014","journal-title":"Acta Neuropathol."},{"key":"B176","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s40478-019-0812-5","article-title":"Synaptic localization of C9orf72 regulates post-synaptic glutamate receptor 1 levels","volume":"7","author":"Xiao","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"B177","doi-asserted-by":"publisher","first-page":"7741","DOI":"10.1523\/JNEUROSCI.0908-18.2018","article-title":"C9orf72 dipeptide repeats cause selective neurodegeneration and cell-autonomous excitotoxicity in Drosophila glutamatergic neurons","volume":"38","author":"Xu","year":"2018","journal-title":"J. Neurosci."},{"key":"B178","doi-asserted-by":"publisher","first-page":"e1601167","DOI":"10.1126\/sciadv.1601167","article-title":"A C9ORF72\/SMCR8-containing complex regulates ULK1 and plays a dual role in autophagy","volume":"2","author":"Yang","year":"2016","journal-title":"Sci. Adv."},{"key":"B179","doi-asserted-by":"publisher","first-page":"9452","DOI":"10.1523\/JNEUROSCI.23-28-09452.2003","article-title":"Neurofilament transport in vivo minimally requires hetero-oligomer formation","volume":"23","author":"Yuan","year":"2003","journal-title":"J. Neurosci."},{"key":"B180","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/mp.2015.99","article-title":"Functions of neurofilaments in synapses","volume":"20","author":"Yuan","year":"","journal-title":"Mol. Psychiatry"},{"key":"B181","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/mp.2015.45","article-title":"Neurofilament subunits are integral components of synapses and modulate neurotransmission and behavior in vivo","volume":"20","author":"Yuan","year":"","journal-title":"Mol. Psychiatry"},{"key":"B182","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.cell.2012.12.029","article-title":"Vesicular glycolysis provides on-board energy for fast axonal transport","volume":"152","author":"Zala","year":"2013","journal-title":"Cell"},{"key":"B184","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature14973","article-title":"The C9orf72 repeat expansion disrupts nucleocytoplasmic transport","volume":"525","author":"Zhang","year":"2015","journal-title":"Nature"},{"key":"B183","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1083\/jcb.139.5.1307","article-title":"Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation","volume":"139","author":"Zhang","year":"1997","journal-title":"J. Cell Biol."},{"key":"B185","doi-asserted-by":"publisher","first-page":"1292.e5","DOI":"10.1016\/j.neuron.2017.08.039","article-title":"RAN translation regulated by muscleblind proteins in myotonic dystrophy type 2","volume":"95","author":"Zu","year":"2017","journal-title":"Neuron"},{"key":"B186","doi-asserted-by":"publisher","first-page":"E4968","DOI":"10.1073\/pnas.1315438110","article-title":"RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia","volume":"110","author":"Zu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"B187","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13024-020-00406-3","article-title":"Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers","volume":"15","author":"Zucchi","year":"2020","journal-title":"Mol. Neurodegener."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.660693\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T05:25:00Z","timestamp":1622525100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.660693\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,1]]},"references-count":188,"alternative-id":["10.3389\/fncel.2021.660693"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2021.660693","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,1]]},"article-number":"660693"}}