{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:56Z","timestamp":1787027816439,"version":"build-2736575974"},"reference-count":187,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["21K15178"],"award-info":[{"award-number":["21K15178"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yukihiko Miyata Memorial Trust for ALS Research","award":["21K15178"],"award-info":[{"award-number":["21K15178"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron disease caused by upper and lower motor neuron death. Despite advances in our understanding of ALS pathogenesis, effective treatment for this fatal disease remains elusive. As aging is a major risk factor for ALS, age-related molecular changes may provide clues for the development of new therapeutic strategies. Dysregulation of age-dependent RNA metabolism plays a pivotal role in the pathogenesis of ALS. In addition, failure of RNA editing at the glutamine\/arginine (Q\/R) site of GluA2 mRNA causes excitotoxicity due to excessive Ca2+ influx through Ca2+-permeable \u03b1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, which is recognized as an underlying mechanism of motor neuron death in ALS. Circular RNAs (circRNAs), a circular form of cognate RNA generated by back-splicing, are abundant in the brain and accumulate with age. Hence, they are assumed to play a role in neurodegeneration. Emerging evidence has demonstrated that age-related dysregulation of RNA editing and changes in circRNA expression are involved in ALS pathogenesis. Herein, we review the potential associations between age-dependent changes in circRNAs and RNA editing, and discuss the possibility of developing new therapies and biomarkers for ALS based on age-related changes in circRNAs and dysregulation of RNA editing.<\/jats:p>","DOI":"10.3390\/cells12101443","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T01:36:48Z","timestamp":1684805808000},"page":"1443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Roles of Aging, Circular RNAs, and RNA Editing in the Pathogenesis of Amyotrophic Lateral Sclerosis: Potential Biomarkers and Therapeutic Targets"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0305-8809","authenticated-orcid":false,"given":"Takashi","family":"Hosaka","sequence":"first","affiliation":[{"name":"Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"},{"name":"University of Tsukuba Hospital\/Jichi Medical University Joint Ibaraki Western Regional Clinical Education Center, Chikusei 308-0813, Japan"},{"name":"Department of Internal Medicine, Ibaraki Western Medical Center, Chikusei 308-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tokyo Medical University, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1056\/NEJM200105313442207","article-title":"Amyotrophic Lateral Sclerosis","volume":"344","author":"Rowland","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic Lateral Sclerosis","volume":"400","author":"Feldman","year":"2022","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12408","DOI":"10.1038\/ncomms12408","article-title":"Projected Increase in Amyotrophic Lateral Sclerosis from 2015 to 2040","volume":"7","author":"Arthur","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMra1603471","article-title":"Amyotrophic Lateral Sclerosis","volume":"377","author":"Brown","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1474-4422(21)00414-2","article-title":"Emerging Insights into the Complex Genetics and Pathophysiology of Amyotrophic Lateral Sclerosis","volume":"21","author":"Goutman","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"712","DOI":"10.3389\/fgene.2018.00712","article-title":"RNA Dysregulation in Amyotrophic Lateral Sclerosis","volume":"9","author":"Butti","year":"2018","journal-title":"Front. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1001\/jamaneurol.2022.3282","article-title":"Amyotrophic Lateral Sclerosis Clinical Trials and Interpretation of Functional End Points and Fluid Biomarkers: A Review","volume":"79","author":"Shefner","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/S0140-6736(96)91680-3","article-title":"Dose-Ranging Study of Riluzole in Amyotrophic Lateral Sclerosis. Amyotrophic Lateral Sclerosis\/Riluzole Study Group II","volume":"347","author":"Lacomblez","year":"1996","journal-title":"Lancet"},{"key":"ref_9","unstructured":"Writing Group, and Edaravone (MCI-186) ALS 19 Study Group (2017). Safety and Efficacy of Edaravone in Well Defined Patients with Amyotrophic Lateral Sclerosis: A Randomised, Double-Blind, Placebo-Controlled Trial. Lancet Neurol., 16, 505\u2013512."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1056\/NEJMoa1916945","article-title":"Trial of Sodium Phenylbutyrate-Taurursodiol for Amyotrophic Lateral Sclerosis","volume":"383","author":"Paganoni","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/j.1474-9726.2011.00726.x","article-title":"Human Aging Is Characterized by Focused Changes in Gene Expression and Deregulation of Alternative Splicing","volume":"10","author":"Harries","year":"2011","journal-title":"Aging Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5894","DOI":"10.1038\/s41598-017-05927-4","article-title":"Gene Expression Reversal Toward Pre-adult Levels in the Aging Human Brain and Age-Related Loss of Cellular Identity","volume":"7","author":"He","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1172\/JCI95145","article-title":"Cellular Senescence in Brain Aging and Neurodegenerative Diseases: Evidence and Perspectives","volume":"128","author":"Baker","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a Risk Factor for Neurodegenerative Disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1093\/nar\/24.21.4152","article-title":"Inverse Splicing of a Discontinuous Pre-mRNA Intron Generates a Circular Exon in a HeLa Cell Nuclear Extract","volume":"24","author":"Braun","year":"1996","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molcel.2014.08.019","article-title":"circRNA Biogenesis Competes with Pre-mRNA Splicing","volume":"56","author":"Meyer","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s12943-017-0663-2","article-title":"CircRNA: Functions and Properties of a Novel Potential Biomarker for Cancer","volume":"16","author":"Meng","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.omtm.2020.05.027","article-title":"Circular RNAs: Promising Molecular Biomarkers of Human Aging-Related Diseases via Functioning as An miRNA Sponge","volume":"18","author":"Ren","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D93","DOI":"10.1093\/nar\/gkab1036","article-title":"CircNet 2.0: An Updated Database for Exploring Circular RNA Regulatory Networks in Cancers","volume":"50","author":"Chen","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1038\/s41598-019-38860-9","article-title":"Circular RNAs Are Temporospatially Regulated Throughout Development and Ageing in the Rat","volume":"9","author":"Mahmoudi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1261\/rna.035667.112","article-title":"Circular RNAs Are Abundant, Conserved, and Associated with ALU Repeats","volume":"19","author":"Jeck","year":"2013","journal-title":"RNA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12429","DOI":"10.1038\/ncomms12429","article-title":"Circular Non-coding RNA ANRIL Modulates Ribosomal RNA Maturation and Atherosclerosis in Humans","volume":"7","author":"Holdt","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.molcel.2015.03.027","article-title":"Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed","volume":"58","author":"Stottmeister","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.cell.2018.12.021","article-title":"The Landscape of Circular RNA in Cancer","volume":"176","author":"Vo","year":"2019","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nsmb.2959","article-title":"Exon-Intron Circular RNAs Regulate Transcription in the Nucleus","volume":"22","author":"Li","year":"2015","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Liu, Y., Su, H., Zhang, J., Liu, Y., Feng, C., and Han, F. (2020). Back-Spliced RNA from Retrotransposon Binds to Centromere and Regulates Centromeric Chromatin Loops in Maize. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000582"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature11993","article-title":"Natural RNA Circles Function as Efficient microRNA Sponges","volume":"495","author":"Hansen","year":"2013","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1093\/nar\/gkw027","article-title":"Foxo3 Circular RNA Retards Cell Cycle Progression via Forming Ternary Complexes with p21 and CDK2","volume":"44","author":"Du","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"38907","DOI":"10.1038\/srep38907","article-title":"CircRNA Accumulation in the Aging Mouse Brain","volume":"6","author":"Gruner","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nn.3975","article-title":"Neural Circular RNAs Are Derived from Synaptic Genes and Regulated by Development and Plasticity","volume":"18","author":"You","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"D\u2019Anca, M., Buccellato, F.R., Fenoglio, C., and Galimberti, D. (2022). Circular RNAs: Emblematic Players of Neurogenesis and Neurodegeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084134"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/path.6021","article-title":"Circular RNAs: Emerging Players in Brain Aging and Neurodegenerative Diseases","volume":"259","author":"Wu","year":"2023","journal-title":"J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"683459","DOI":"10.3389\/fcell.2021.683459","article-title":"The Ageing Brain: Molecular and Cellular Basis of Neurodegeneration","volume":"9","author":"Azam","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/cr.2015.82","article-title":"Circular RNA Is Enriched and Stable in Exosomes: A Promising Biomarker for Cancer Diagnosis","volume":"25","author":"Li","year":"2015","journal-title":"Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s00109-017-1582-9","article-title":"A Map of Human Circular RNAs in Clinically Relevant Tissues","volume":"95","author":"Maass","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nrm.2015.4","article-title":"A-to-I Editing of Coding and Non-coding RNAs by ADARs","volume":"17","author":"Nishikura","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/19992","article-title":"Regulation of Alternative Splicing by RNA Editing","volume":"399","author":"Rueter","year":"1999","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"200085","DOI":"10.1098\/rsob.200085","article-title":"What Do Editors Do? Understanding the Physiological Functions of A-to-I RNA Editing by Adenosine Deaminase Acting on RNAs","volume":"10","author":"Walkley","year":"2020","journal-title":"Open Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nsmb1041","article-title":"Modulation of microRNA Processing and Expression Through RNA Editing by ADAR Deaminases","volume":"13","author":"Yang","year":"2006","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.celrep.2014.12.019","article-title":"Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals","volume":"10","author":"Ivanov","year":"2015","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"711564","DOI":"10.3389\/fncir.2021.711564","article-title":"Calcium Permeable-AMPA Receptors and Excitotoxicity in Neurological Disorders","volume":"15","author":"Guo","year":"2021","journal-title":"Front. Neural Circuits"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/S0896-6273(02)00693-1","article-title":"RNA Editing at arg607 Controls AMPA Receptor Exit from the Endoplasmic Reticulum","volume":"34","author":"Greger","year":"2002","journal-title":"Neuron"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hideyama, T., Teramoto, S., Hachiga, K., Yamashita, T., and Kwak, S. (2012). Co-occurrence of TDP-43 Mislocalization with Reduced Activity of an RNA Editing Enzyme, ADAR2, in Aged Mouse Motor Neurons. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043469"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/s41556-022-00959-z","article-title":"ADAR1 Downregulation by Autophagy Drives Senescence Independently of RNA Editing by Enhancing p16INK4a Levels","volume":"24","author":"Hao","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sebastiani, P., Montano, M., Puca, A., Solovieff, N., Kojima, T., Wang, M.C., Melista, E., Meltzer, M., Fischer, S.E., and Andersen, S. (2009). RNA Editing Genes Associated with Extreme Old Age in Humans and with Lifespan in C. elegans. PLoS ONE, 4.","DOI":"10.1371\/annotation\/387f8074-5f80-4bdd-bb0b-b36d49a16ac0"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/j.neurobiolaging.2014.11.013","article-title":"Glutamate Presynaptic Vesicular Transporter and Postsynaptic Receptor Levels Correlate with Spatial Memory Status in Aging Rat Models","volume":"36","author":"Quirion","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"446","DOI":"10.3389\/fnmol.2017.00446","article-title":"AMPA Receptor Trafficking in Natural and Pathological Aging","volume":"10","author":"Jurado","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e13657","DOI":"10.1111\/acel.13657","article-title":"Regulation and roles of RNA modifications in aging-related diseases","volume":"21","author":"Jiapaer","year":"2022","journal-title":"Aging Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s13578-021-00700-7","article-title":"Role of FoxO Transcription Factors in Aging and Age-Related Metabolic and Neurodegenerative Diseases","volume":"11","author":"Du","year":"2021","journal-title":"Cell Biosci."},{"key":"ref_50","first-page":"1402","article-title":"Foxo3 Circular RNA Promotes Cardiac Senescence by Modulating Multiple Factors Associated with Stress and Senescence Responses","volume":"38","author":"Du","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s11357-019-00120-z","article-title":"circRNAs Expressed in Human Peripheral Blood Are Associated with Human Aging Phenotypes, Cellular Senescence and Mouse Lifespan","volume":"42","author":"Haque","year":"2020","journal-title":"GeroScience"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.tcb.2008.07.007","article-title":"The Let-7 Family of microRNAs","volume":"18","author":"Roush","year":"2008","journal-title":"Trends Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nn.3113","article-title":"An Unconventional Role for miRNA: Let-7 Activates Toll-Like Receptor 7 and Causes Neurodegeneration","volume":"15","author":"Lehmann","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6069682","DOI":"10.1155\/2022\/6069682","article-title":"Inhibiting Autophagy Pathway of PI3K\/AKT\/mTOR Promotes Apoptosis in SK-N-SH Cell Model of Alzheimer\u2019s Disease","volume":"2022","author":"Pang","year":"2022","journal-title":"J. Healthc. Eng."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1093\/nar\/gkw1201","article-title":"Identification of Senescence-Associated Circular RNAs (SAC-RNAs) Reveals Senescence Suppressor CircPVT1","volume":"45","author":"Panda","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"105297","DOI":"10.1016\/j.tiv.2021.105297","article-title":"Circular RNA PVT1 Inhibits Tendon Stem\/Progenitor Cell Senescence by Sponging microRNA-199a-5p","volume":"79","author":"Han","year":"2022","journal-title":"Toxicol. Vitr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1007\/s11064-016-2110-y","article-title":"Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders","volume":"42","author":"Wencel","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Sousa, C., and Mendes, A.F. (2022). Monoterpenes as Sirtuin-1 Activators: Therapeutic Potential in Aging and Related Diseases. Biomolecules, 12.","DOI":"10.3390\/biom12070921"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41576-022-00534-0","article-title":"Biological Roles of Adenine Methylation in RNA","volume":"24","author":"Boulias","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.omtn.2022.01.007","article-title":"Novel Insights into the Interaction Between N6-Methyladenosine Modification and Circular RNA","volume":"27","author":"Xu","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/mmr.2023.12942","article-title":"Differential Methylation of circRNA m6A in an APP\/PS1 Alzheimer\u2019s Disease Mouse Model","volume":"27","author":"Zhang","year":"2023","journal-title":"Mol. Med. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Bayer, C., Pitschelatow, G., Hannemann, N., Linde, J., Reichard, J., Pensold, D., and Zimmer-Bensch, G. (2020). DNA Methyltransferase 1 (DNMT1) Acts on Neurodegeneration by Modulating Proteostasis-Relevant Intracellular Processes. Int. J. Mol. Sci., 21.","DOI":"10.1101\/2020.07.10.197442"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1093\/hmg\/ddp222","article-title":"DNA Hypomethylation Restricted to the Murine Forebrain Induces Cortical Degeneration and Impairs Postnatal Neuronal Maturation","volume":"18","author":"Hutnick","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1093\/cercor\/bhw341","article-title":"The DNA Methyltransferase 1 (DNMT1) Controls the Shape and Dynamics of Migrating POA-Derived Interneurons Fated for the Murine Cerebral Cortex","volume":"27","author":"Pensold","year":"2017","journal-title":"Cereb. Cortex"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"eabe8511","DOI":"10.1126\/sciadv.abe8511","article-title":"Mutation-Induced DNMT1 Cleavage Drives Neurodegenerative Disease","volume":"7","author":"Wang","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5829","DOI":"10.1038\/s41388-018-0369-y","article-title":"A Circular RNA Circ-DNMT1 Enhances Breast Cancer Progression by Activating Autophagy","volume":"37","author":"Du","year":"2018","journal-title":"Oncogene"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3594","DOI":"10.1038\/s41467-020-17435-7","article-title":"CircGRIA1 Shows an Age-Related Increase in Male Macaque Brain and Regulates Synaptic Plasticity and Synaptogenesis","volume":"11","author":"Xu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e12785","DOI":"10.1111\/acel.12785","article-title":"Extracellular RNA Profiles with Human Age","volume":"17","author":"Dluzen","year":"2018","journal-title":"Aging Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41421-018-0050-1","article-title":"Annotation and Functional Clustering of circRNA Expression in Rhesus Macaque Brain During Aging","volume":"4","author":"Xu","year":"2018","journal-title":"Cell Discov."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1080\/15476286.2020.1867797","article-title":"Adenosine-to-Inosine RNA Editing in Neurological Development and Disease","volume":"18","author":"Yang","year":"2021","journal-title":"RNA Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41576-018-0006-1","article-title":"A-to-I RNA Editing\u2014Immune Protector and Transcriptome Diversifier","volume":"19","author":"Eisenberg","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/978-3-319-89689-2_3","article-title":"RNA Editing Deficiency in Neurodegeneration","volume":"20","author":"Lorenzini","year":"2018","journal-title":"Adv. Neurobiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1038\/s41467-017-01458-8","article-title":"RNA Editing by ADAR1 Leads to Context-Dependent Transcriptome-Wide Changes in RNA Secondary Structure","volume":"8","author":"Solomon","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.arr.2010.02.002","article-title":"RNA Surveillance-an Emerging Role for RNA Regulatory Networks in Aging","volume":"10","author":"Montano","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1101\/gr.089409.108","article-title":"Large-Scale mRNA Sequencing Determines Global Regulation of RNA Editing During Brain Development","volume":"19","author":"Wahlstedt","year":"2009","journal-title":"Genome Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Shtrichman, R., Germanguz, I., Mandel, R., Ziskind, A., Nahor, I., Safran, M., Osenberg, S., Sherf, O., Rechavi, G., and Itskovitz-Eldor, J. (2012). Altered A-to-I RNA Editing in Human Embryogenesis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041576"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Hosaka, T., Tsuji, H., and Kwak, S. (2021). RNA Editing: A New Therapeutic Target in Amyotrophic Lateral Sclerosis and Other Neurological Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010958"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/gm508","article-title":"Adenosine-to-Inosine RNA Editing and Human Disease","volume":"5","author":"Slotkin","year":"2013","journal-title":"Genome Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.ajhg.2020.02.015","article-title":"Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual Disability, and Seizures","volume":"106","author":"Tan","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1136\/jmedgenet-2020-107048","article-title":"Biallelic Variants in ADARB1, Encoding a dsRNA-Specific Adenosine Deaminase, Cause a Severe Developmental and Epileptic Encephalopathy","volume":"58","author":"Maroofian","year":"2021","journal-title":"J. Med. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1136\/jmedgenet-2013-102038","article-title":"A Type I Interferon Signature Identifies Bilateral Striatal Necrosis Due to Mutations in ADAR1","volume":"51","author":"Livingston","year":"2014","journal-title":"J. Med. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.mad.2010.06.001","article-title":"Age-Related Gene-Specific Changes of A-to-I mRNA Editing in the Human Brain","volume":"131","author":"Nicholas","year":"2010","journal-title":"Mech. Ageing Dev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10522-013-9433-8","article-title":"A-to-I RNA Editing Does Not Change with Age in the Healthy Male Rat Brain","volume":"14","author":"Holmes","year":"2013","journal-title":"Biogerontology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1038\/s41593-019-0501-5","article-title":"An Atlas of Cortical Circular RNA Expression in Alzheimer Disease Brains Demonstrates Clinical and Pathological Associations","volume":"22","author":"Dube","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Aquilina-Reid, C., Brennan, S., Curry-Hyde, A., Teunisse, G.M., The Nygc Als Consortium, and Janitz, M. (2022). Circular RNA Expression and Interaction Patterns Are Perturbed in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314665"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"9832","DOI":"10.18632\/aging.204450","article-title":"Transcriptomic Analysis of Human ALS Skeletal Muscle Reveals a Disease-Specific Pattern of Dysregulated circRNAs","volume":"14","author":"Tsitsipatis","year":"2022","journal-title":"Aging"},{"key":"ref_87","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_88","doi-asserted-by":"crossref","first-page":"14741","DOI":"10.1038\/ncomms14741","article-title":"FUS Affects Circular RNA Expression in Murine Embryonic Stem Cell-Derived Motor Neurons","volume":"8","author":"Errichelli","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Colantoni, A., Capauto, D., Alfano, V., D\u2019Ambra, E., D\u2019Uva, S., Tartaglia, G.G., and Morlando, M. (2023). FUS Alters circRNA Metabolism in Human Motor Neurons Carrying the ALS-Linked P525L Mutation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043181"},{"key":"ref_90","doi-asserted-by":"crossref","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":"Mackenzie","year":"2011","journal-title":"Neuron"},{"key":"ref_91","doi-asserted-by":"crossref","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":"ref_92","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S1474-4422(14)70233-9","article-title":"C9orf72 Expansions in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis","volume":"14","author":"Rohrer","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4908","DOI":"10.1038\/s41467-021-25082-9","article-title":"Nuclear Export and Translation of Circular Repeat-Containing Intronic RNA in C9ORF72-ALS\/FTD","volume":"12","author":"Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00401-016-1587-4","article-title":"ALS and FTD: An Epigenetic Perspective","volume":"132","author":"Belzil","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"102428","DOI":"10.1016\/j.jbc.2022.102428","article-title":"Densely Methylated DNA Traps Methyl-CpG-Binding Domain Protein 2 but Permits Free Diffusion by Methyl-CpG-Binding Domain Protein 3","volume":"298","author":"Leighton","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e662","DOI":"10.1002\/ctm2.662","article-title":"circKCNN2 Suppresses the Recurrence of Hepatocellular Carcinoma at Least Partially via Regulating miR-520c-3p\/methyl-DNA-binding Domain Protein 2 Axis","volume":"12","author":"Liu","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neurobiolaging.2020.03.017","article-title":"Assessing Circular RNAs in Alzheimer\u2019s Disease and Frontotemporal Lobar Degeneration","volume":"92","author":"Alcolea","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/cbf.3724","article-title":"Relation Between the Circular and Linear Form of the Elongator Acetyltransferase Complex Subunit 3 in the Progression of Triple-Negative Breast Cancer","volume":"40","author":"Barznegar","year":"2022","journal-title":"Cell Biochem. Funct."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1042\/BJ20070578","article-title":"Gcn5- and Elp3-Induced Histone H3 Acetylation Regulates hsp70 Gene Transcription in Yeast","volume":"409","author":"Han","year":"2008","journal-title":"Biochem. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.gene.2018.10.043","article-title":"CircRNA has_circ_0078710 Acts as the Sponge of microRNA-31 Involved in Hepatocellular Carcinoma Progression","volume":"683","author":"Xie","year":"2019","journal-title":"Gene"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/s41419-021-04059-y","article-title":"Circ-SIRT1 Inhibits Cardiac Hypertrophy via Activating SIRT1 to Promote Autophagy","volume":"12","author":"Wang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e1296","DOI":"10.1038\/cddis.2014.247","article-title":"Tissue-Specific Deregulation of Selected HDACs Characterizes ALS Progression in Mouse Models: Pharmacological Characterization of SIRT1 and SIRT2 Pathways","volume":"5","author":"Valle","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1021\/acschemneuro.7b00297","article-title":"Neurodegenerative Disease Proteinopathies Are Connected to Distinct Histone Post-translational Modification Landscapes","volume":"9","author":"Chen","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s10863-021-09895-3","article-title":"Silencing circRNA LRP6 Down-Regulates PRMT1 to Improve the Streptozocin-Induced Pancreatic Beta-Cell Injury and Insulin Secretion by Sponging miR-9-5p","volume":"53","author":"Ma","year":"2021","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"40474","DOI":"10.1038\/srep40474","article-title":"Sequestration of PRMT1 and Nd1-L mRNA into ALS-Linked FUS Mutant R521C-Positive Aggregates Contributes to Neurite Degeneration upon Oxidative Stress","volume":"7","author":"Jun","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000089620","article-title":"Excitotoxicity and Amyotrophic Lateral Sclerosis","volume":"2","author":"Dewil","year":"2005","journal-title":"Neurodegener. Dis."},{"key":"ref_107","doi-asserted-by":"crossref","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":"ref_108","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.neuron.2018.10.018","article-title":"The AMPA Receptor Code of Synaptic Plasticity","volume":"100","author":"Diering","year":"2018","journal-title":"Neuron"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/path.5351","article-title":"Dysregulation of AMPA Receptor Subunit Expression in Sporadic ALS Post-Mortem Brain","volume":"250","author":"Gregory","year":"2020","journal-title":"J. Pathol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1038\/ncomms8098","article-title":"FUS Regulates AMPA Receptor Function and FTLD\/ALS-Associated Behaviour via GluA1 mRNA Stabilization","volume":"6","author":"Udagawa","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"7635","DOI":"10.1007\/s12035-018-0884-4","article-title":"A Regulatory Circuitry Between Gria2, miR-409, and miR-495 Is Affected by ALS FUS Mutation in ESC-Derived Motor Neurons","volume":"55","author":"Capauto","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41467-017-02729-0","article-title":"C9ORF72 Repeat Expansion Causes Vulnerability of Motor Neurons to Ca2+-Permeable AMPA Receptor-Mediated Excitotoxicity","volume":"9","author":"Selvaraj","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","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 Rep."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"jcs248534","DOI":"10.1242\/jcs.248534","article-title":"Endoplasmic Reticulum-Mitochondria Signaling in Neurons and Neurodegenerative Diseases","volume":"135","author":"Markovinovic","year":"2022","journal-title":"J. Cell Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.15252\/emmm.201606403","article-title":"Mitochondria-Associated Membrane Collapse Is a Common Pathomechanism in SIGMAR1- and SOD1-Linked ALS","volume":"8","author":"Watanabe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41419-017-0022-7","article-title":"Disruption of ER-Mitochondria Signalling in Fronto-temporal Dementia and Related Amyotrophic Lateral Sclerosis","volume":"9","author":"Lau","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e21688","DOI":"10.1096\/fj.202100137R","article-title":"Novel Reporters of Mitochondria-Associated Membranes (MAM), MAMtrackers, Demonstrate MAM Disruption as a Common Pathological Feature in Amyotrophic Lateral Sclerosis","volume":"35","author":"Sakai","year":"2021","journal-title":"FASEB J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/ana.22534","article-title":"A Mutation in Sigma-1 Receptor Causes Juvenile Amyotrophic Lateral Sclerosis","volume":"70","author":"Bohlega","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1016\/j.bbagen.2014.08.012","article-title":"Methyl Pyruvate Rescues Mitochondrial Damage Caused by SIGMAR1 Mutation Related to Amyotrophic Lateral Sclerosis","volume":"1840","author":"Tagashira","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/ana.22274","article-title":"Sigma Nonopioid Intracellular Receptor 1 Mutations Cause Frontotemporal Lobar Degeneration-Motor Neuron Disease","volume":"68","author":"Luty","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1038\/cdd.2017.88","article-title":"The ALS-Linked E102Q Mutation in Sigma Receptor-1 Leads to ER Stress-Mediated Defects in Protein Homeostasis and Dysregulation of RNA-Binding Proteins","volume":"24","author":"Dreser","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1080\/15548627.2017.1356975","article-title":"Circular RNA HIPK2 Regulates Astrocyte Activation via Cooperation of Autophagy and ER Stress by Targeting MIR124-2HG","volume":"13","author":"Huang","year":"2017","journal-title":"Autophagy"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1065897","DOI":"10.3389\/fnins.2022.1065897","article-title":"Inhibition by rno-circRNA-013017 of the Apoptosis of Motor Neurons in Anterior Horn and Descending Axonal Degeneration in Rats After Traumatic Spinal Cord Injury","volume":"16","author":"Qin","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/ana.410240314","article-title":"The Neuroexcitotoxic Amino Acids Glutamate and Aspartate Are Altered in the Spinal Cord and Brain in Amyotrophic Lateral Sclerosis","volume":"24","author":"Plaitakis","year":"1988","journal-title":"Ann. Neurol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/ana.410280106","article-title":"Abnormal Excitatory Amino Acid Metabolism in Amyotrophic Lateral Sclerosis","volume":"28","author":"Rothstein","year":"1990","journal-title":"Ann. Neurol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1006\/neur.1995.0026","article-title":"CSF and Plasma Amino Acid Levels in Motor Neuron Disease: Elevation of CSF Glutamate in a Subset of Patients","volume":"4","author":"Shaw","year":"1995","journal-title":"Neurodegeneration"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0022-510X(01)00661-X","article-title":"Glutamate Levels in Cerebrospinal Fluid in Amyotrophic Lateral Sclerosis: A Reappraisal Using a New HPLC Method with Coulometric Detection in a Large Cohort of Patients","volume":"193","author":"Bensimon","year":"2002","journal-title":"J. Neurol. Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1056\/NEJM199205283262204","article-title":"Decreased Glutamate Transport by the Brain and Spinal Cord in Amyotrophic Lateral Sclerosis","volume":"326","author":"Rothstein","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/0014-2999(93)90037-I","article-title":"The Neuroprotective Agent Riluzole Inhibits Release of Glutamate and Aspartate from Slices of Hippocampal Area CA1","volume":"250","author":"Martin","year":"1993","journal-title":"Eur. J. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1056\/NEJM199403033300901","article-title":"A Controlled Trial of Riluzole in Amyotrophic Lateral Sclerosis. ALS\/Riluzole Study Group","volume":"330","author":"Bensimon","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S1474-4422(18)30054-1","article-title":"Stage at Which Riluzole Treatment Prolongs Survival in Patients with Amyotrophic Lateral Sclerosis: A Retrospective Analysis of Data from a Dose-Ranging Study","volume":"17","author":"Fang","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/4561","article-title":"Neurological Dysfunctions in Mice Expressing Different Levels of the Q\/R Site-Unedited AMPAR Subunit GluR-B","volume":"2","author":"Feldmeyer","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/35017558","article-title":"Point Mutation in an AMPA Receptor Gene Rescues Lethality in Mice Deficient in the RNA-Editing Enzyme ADAR2","volume":"406","author":"Higuchi","year":"2000","journal-title":"Nature"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0896-6273(02)00760-2","article-title":"A-to-I Editing: New and Old Sites, Functions and Speculations","volume":"35","author":"Seeburg","year":"2002","journal-title":"Neuron"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/427801a","article-title":"Glutamate Receptors: RNA Editing and Death of Motor Neurons","volume":"427","author":"Kawahara","year":"2004","journal-title":"Nature"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.nbd.2011.12.033","article-title":"Profound Downregulation of the RNA Editing Enzyme ADAR2 in ALS Spinal Motor Neurons","volume":"45","author":"Hideyama","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"11917","DOI":"10.1523\/JNEUROSCI.2021-10.2010","article-title":"Induced Loss of ADAR2 Engenders Slow Death of Motor Neurons from Q\/R Site-Unedited GluR2","volume":"30","author":"Hideyama","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1038\/ncomms2303","article-title":"A Role for Calpain-Dependent Cleavage of TDP-43 in Amyotrophic Lateral Sclerosis Pathology","volume":"3","author":"Yamashita","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.brainres.2013.12.011","article-title":"The Molecular Link Between Inefficient GluA2 Q\/R Site-RNA Editing and TDP-43 Pathology in Motor Neurons of Sporadic Amyotrophic Lateral Sclerosis Patients","volume":"1584","author":"Yamashita","year":"2014","journal-title":"Brain Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neures.2005.09.006","article-title":"Underediting of GluR2 mRNA, a Neuronal Death Inducing Molecular Change in Sporadic ALS, Does Not Occur in Motor Neurons in ALS1 or SBMA","volume":"54","author":"Kawahara","year":"2006","journal-title":"Neurosci. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00401-010-0678-x","article-title":"TDP-43 Pathology in Sporadic ALS Occurs in Motor Neurons Lacking the RNA Editing Enzyme ADAR2","volume":"120","author":"Aizawa","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.trsl.2018.10.002","article-title":"Epigenetics in Amyotrophic Lateral Sclerosis: A Role for Histone Post-translational Modifications in Neurodegenerative Disease","volume":"204","author":"Bennett","year":"2019","journal-title":"Transl. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1097\/WNR.0000000000000474","article-title":"Differential Regulation of Expression of RNA-Editing Enzymes, ADAR1 and ADAR2, by 5-aza-2\u2032-deoxycytidine and Trichostatin A in Human Neuronal SH-SY5Y Cells","volume":"26","author":"Uchida","year":"2015","journal-title":"NeuroReport"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jocn.2015.12.039","article-title":"Deficient RNA-Editing Enzyme ADAR2 in an Amyotrophic Lateral Sclerosis Patient with a FUS(P525L) Mutation","volume":"32","author":"Aizawa","year":"2016","journal-title":"J. Clin. Neurosci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00401-019-01999-w","article-title":"ADAR2 Mislocalization and Widespread RNA Editing Aberrations in C9orf72-Mediated ALS\/FTD","volume":"138","author":"Moore","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/jnc.15445","article-title":"Proline-Arginine Poly-dipeptide Encoded by the C9orf72 Repeat Expansion Inhibits Adenosine Deaminase Acting on RNA","volume":"158","author":"Suzuki","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.celrep.2016.03.058","article-title":"The Biogenesis of Nascent Circular RNAs","volume":"15","author":"Zhang","year":"2016","journal-title":"Cell Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cell.2014.09.001","article-title":"Complementary Sequence-Mediated Exon Circularization","volume":"159","author":"Zhang","year":"2014","journal-title":"Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cell.2017.12.038","article-title":"Human ADAR1 Prevents Endogenous RNA from Triggering Translational Shutdown","volume":"172","author":"Chung","year":"2018","journal-title":"Cell"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nature21715","article-title":"DHX9 Suppresses RNA Processing Defects Originating from the Alu Invasion of the Human Genome","volume":"544","author":"Maticzka","year":"2017","journal-title":"Nature"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s12943-020-01268-5","article-title":"Circular RNA hsa_circ_0004872 Inhibits Gastric Cancer Progression via the miR-224\/Smad4\/ADAR1 Successive Regulatory Circuit","volume":"19","author":"Ma","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"102184","DOI":"10.1016\/j.jbc.2022.102184","article-title":"RNA Editing Enzyme ADAR1 Controls miR-381-3p-mediated Expression of Multidrug Resistance Protein MRP4 via Regulation of circRNA in Human Renal Cells","volume":"298","author":"Omata","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neures.2018.11.005","article-title":"ADAR2-Dependent A-to-I RNA Editing in the Extracellular Linear and Circular RNAs","volume":"147","author":"Hosaka","year":"2019","journal-title":"Neurosci. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s00395-022-00940-9","article-title":"Reduction of A-to-I RNA Editing in the Failing Human Heart Regulates Formation of Circular RNAs","volume":"117","author":"Kokot","year":"2022","journal-title":"Basic Res. Cardiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.tig.2021.04.014","article-title":"Emerging Functions of Circular RNA in Aging","volume":"37","author":"Kim","year":"2021","journal-title":"Trends Genet."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"8052","DOI":"10.1007\/s12035-019-1627-x","article-title":"Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis","volume":"56","author":"Dolinar","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1756-6606-6-26","article-title":"Altered microRNA Expression Profile in Amyotrophic Lateral Sclerosis: A Role in the Regulation of NFL mRNA Levels","volume":"6","author":"Droppelmann","year":"2013","journal-title":"Mol. Brain"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fnmol.2018.00106","article-title":"Differential Expression of Several miRNAs and the Host Genes AATK and DNM2 in Leukocytes of Sporadic ALS Patients","volume":"11","author":"Vrabec","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Ravnik-Glava\u010d, M., and Glava\u010d, D. (2020). Circulating RNAs as Potential Biomarkers in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051714"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1038\/ng.2434","article-title":"Inhibition of RNA Lariat Debranching Enzyme Suppresses TDP-43 Toxicity in ALS Disease Models","volume":"44","author":"Armakola","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Martin, L.J., Adams, D.A., Niedzwiecki, M.V., and Wong, M. (2022). Aberrant DNA and RNA Methylation Occur in Spinal Cord and Skeletal Muscle of Human SOD1 Mouse Models of ALS and in Human ALS: Targeting DNA Methylation Is Therapeutic. Cells, 11.","DOI":"10.3390\/cells11213448"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1161\/CIRCULATIONAHA.120.045765","article-title":"Extracellular Vesicle-Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models","volume":"142","author":"Yang","year":"2020","journal-title":"Circulation"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"e12185","DOI":"10.1002\/jev2.12185","article-title":"Extracellular Vesicle-Mediated Delivery of circDYM Alleviates CUS-Induced Depressive-Like Behaviours","volume":"11","author":"Yu","year":"2022","journal-title":"J. Extracell. Vesicles"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1002\/emmm.201302935","article-title":"Rescue of Amyotrophic Lateral Sclerosis Phenotype in a Mouse Model by Intravenous AAV9-ADAR2 Delivery to Motor Neurons","volume":"5","author":"Yamashita","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.physbeh.2009.03.029","article-title":"Affect-Related Behaviors in Mice Misexpressing the RNA Editing Enzyme ADAR2","volume":"97","author":"Singh","year":"2009","journal-title":"Physiol. Behav."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1056\/NEJMoa2005056","article-title":"SOD1 Suppression with Adeno-Associated Virus and MicroRNA in Familial ALS","volume":"383","author":"Mueller","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","article-title":"Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS","volume":"387","author":"Miller","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.omtn.2022.04.007","article-title":"Preclinical Evaluation of WVE-004, Aninvestigational Stereopure Oligonucleotide Forthe Treatment of C9orf72-Associated ALS or FTD","volume":"28","author":"Liu","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1056\/NEJMoa1708538","article-title":"Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant","volume":"377","author":"George","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1056\/NEJMoa1708483","article-title":"AAV5-Factor VIII Gene Transfer in Severe Hemophilia A","volume":"377","author":"Rangarajan","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/brain\/awy331","article-title":"Gene Therapy Improves Motor and Mental Function of Aromatic L-Amino Acid Decarboxylase Deficiency","volume":"142","author":"Kojima","year":"2019","journal-title":"Brain"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0022-510X(00)00414-7","article-title":"Ca2+-Permeable AMPA Receptors and Selective Vulnerability of Motor Neurons","volume":"180","author":"Vandenberghe","year":"2000","journal-title":"J. Neurol. Sci."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0304-3940(03)00314-8","article-title":"The AMPA Receptor Antagonist NBQX Prolongs Survival in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis","volume":"343","author":"Leyssen","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"28649","DOI":"10.1038\/srep28649","article-title":"The AMPA Receptor Antagonist Perampanel Robustly Rescues Amyotrophic Lateral Sclerosis (ALS) Pathology in Sporadic ALS Model Mice","volume":"6","author":"Akamatsu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/mus.27328","article-title":"Cortical Excitability Threshold Can Be Increased by the AMPA Blocker Perampanel in Amyotrophic Lateral Sclerosis","volume":"64","author":"Oskarsson","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"e202101193","DOI":"10.26508\/lsa.202101193","article-title":"Testing of the Therapeutic Efficacy and Safety of AMPA Receptor RNA Aptamers in an ALS Mouse Model","volume":"5","author":"Akamatsu","year":"2022","journal-title":"Life Sci. Alliance"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00415-021-10670-y","article-title":"Randomized Phase 2 Study of Perampanel for Sporadic Amyotrophic Lateral Sclerosis","volume":"269","author":"Aizawa","year":"2022","journal-title":"J. Neurol."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Lai, M.C., Tzeng, R.C., Huang, C.W., and Wu, S.N. (2019). The Novel Direct Modulatory Effects of Perampanel, an Antagonist of AMPA Receptors, on Voltage-Gated Sodium and M-Type Potassium Currents. Biomolecules, 9.","DOI":"10.3390\/biom9100638"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3389\/fncel.2019.00080","article-title":"Perampanel Affects Up-Stream Regulatory Signaling Pathways of GluA1 Phosphorylation in Normal and Epileptic Rats","volume":"13","author":"Kim","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1111\/j.1460-9568.2005.04431.x","article-title":"Memantine Prolongs Survival in an Amyotrophic Lateral Sclerosis Mouse Model","volume":"22","author":"Wang","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3109\/17482968.2010.498521","article-title":"A Randomized, Placebo-Controlled Trial of Memantine for Functional Disability in Amyotrophic Lateral Sclerosis","volume":"11","author":"Pinto","year":"2010","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1212\/WNL.0000000000002507","article-title":"A Randomized Trial of Mexiletine in ALS: Safety and Effects on Muscle Cramps and Progression","volume":"86","author":"Weiss","year":"2016","journal-title":"Neurology"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/mus.27146","article-title":"Effects of Mexiletine on Hyperexcitability in Sporadic Amyotrophic Lateral Sclerosis: Preliminary Findings from a Small Phase II Randomized Controlled Trial","volume":"63","author":"Weiss","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3109\/21678421.2015.1038277","article-title":"A Single Blind Randomized Controlled Clinical Trial of Mexiletine in Amyotrophic Lateral Sclerosis: Efficacy and Safety of Sodium Channel Blocker Phase II Trial","volume":"16","author":"Shibuya","year":"2015","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_186","doi-asserted-by":"crossref","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":"ref_187","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1001\/jamaneurol.2020.4300","article-title":"Effect of Ezogabine on Cortical and Spinal Motor Neuron Excitability in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial","volume":"78","author":"Wainger","year":"2021","journal-title":"JAMA Neurol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/10\/1443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:39:59Z","timestamp":1760125199000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/10\/1443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,22]]},"references-count":187,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["cells12101443"],"URL":"https:\/\/doi.org\/10.3390\/cells12101443","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,22]]}}}