{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T07:03:34Z","timestamp":1774422214626,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS\u2014with predominant atrophy, muscle weakness, and fasciculations\u2014and survival of 3 to 5 years following diagnosis. In the present review, we performed a literature search to provide an update on the etiology and pathophysiological mechanisms involved in ALS. There are two types of ALS: the familial form with genetic involvement, and the sporadic form with a multifactorial origin. ALS pathophysiology is characterized by involvement of multiple processes, including oxidative stress, glutamate excitotoxicity, and neuroinflammation. Moreover, it is proposed that conditioning risk factors affect ALS development, such as susceptibility to neurodegeneration in motor neurons, the intensity of performed physical activity, and intestinal dysbiosis with involvement of the enteric nervous system, which supports the existing theories of disease generation. To improve patients\u2019 prognosis and survival, it is necessary to further deepen our understanding of the etiopathogenesis of ALS.<\/jats:p>","DOI":"10.3390\/cimb45040217","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T05:57:50Z","timestamp":1681106270000},"page":"3315-3332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Role of Oxidative Stress on the Etiology and Pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and Its Relation with the Enteric Nervous System"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2455-680X","authenticated-orcid":false,"given":"Laura","family":"L\u00f3pez-Pingarr\u00f3n","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology and Legal and Forensic Medicine, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3036-3211","authenticated-orcid":false,"given":"Henrique","family":"Almeida","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Porto University, 4200-135 Porto, Portugal"},{"name":"Department of Biomedicine, Faculty of Medicine, Porto University, 4200-319 Porto, Portugal"},{"name":"Department of Obstetrics and Gynecology, Hospital-CUF Porto, 4100-180 Porto, Portugal"}]},{"given":"Marisol","family":"Soria-Aznar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and Legal and Forensic Medicine, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain"}]},{"given":"Marcos C.","family":"Reyes-Gonzales","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and Legal and Forensic Medicine, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain"}]},{"given":"Mar\u00eda Pilar","family":"Terr\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Health Sciences, University of Badajoz, 06006 Badajoz, Spain"}]},{"given":"Joaqu\u00edn J.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and Legal and Forensic Medicine, Faculty of Medicine, University of Zaragoza, 50009 Zaragoza, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: A clinical review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_2","first-page":"3141","article-title":"Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases","volume":"Volume 2","author":"Fauci","year":"2018","journal-title":"Harrison\u2019s Principles of Internal Medicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1159\/000499485","article-title":"Estimating Amyotrophic Lateral Sclerosis and Motor Neuron Disease Prevalence in Portugal Using a Pharmaco-Epidemiological Approach and a Bayesian Multiparameter Evidence Synthesis Model","volume":"53","author":"Conde","year":"2019","journal-title":"Neuroepidemiology"},{"key":"ref_4","first-page":"102158","article-title":"Amyotrophic lateral sclerosis (ALS) from Primary Care. Epidemiology and clinical-care characteristics","volume":"53","author":"Azagra","year":"2021","journal-title":"Aten. Primaria"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1080\/21678421.2021.1891249","article-title":"Clinical features and incidence trends of amyotrophic lateral sclerosis in Navarre, Spain, 2007\u20132018: A population-based study","volume":"22","author":"Pagola","year":"2021","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nowicka, N., Juranek, J., Juranek, J.K., and Wojtkiewicz, J. (2019). Risk Factors and Emerging Therapies in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112616"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.3389\/fnins.2019.01310","article-title":"ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?","volume":"13","author":"Mejzini","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_8","unstructured":"Maragakis, N.J., and Galvez-Jimenez, N. (2021). Epidemiology and Pathogenesis of Amyotrophic Lateral Sclerosis, UpToDate Inc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"a024117","DOI":"10.1101\/cshperspect.a024117","article-title":"Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)","volume":"7","author":"Grad","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_10","unstructured":"Elman, L.B., and McCluskey, L. (2021). Clinical Features of Amyotrophic Lateral Sclerosis and Other Forms of Motor Neuron Disease, UpToDate Inc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.neurol.2021.03.001","article-title":"Phenotypic variability in amyotrophic lateral sclerosis","volume":"177","author":"Couratier","year":"2021","journal-title":"Rev. Neurol."},{"key":"ref_12","unstructured":"Elman, L., and McClusckey, L. (2021). Diagnosis of Amyotrophic Lateral Sclerosis and Other Forms of Motor Neuron Disease, UpToDate Inc."},{"key":"ref_13","first-page":"107986","article-title":"Disease-modifying therapies in amyotrophic lateral sclerosis","volume":"167","author":"Mazzini","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sever, B., Ciftci, H., DeMirci, H., Sever, H., Ocak, F., Yulug, B., Tateishi, H., Tateishi, T., Otsuka, M., and Fujita, M. (2022). Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052400"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3389\/fphys.2020.00063","article-title":"Antioxidant Alternatives in the Treatment of Amyotrophic Lateral Sclerosis: A Comprehensive Review","volume":"11","author":"Moreno","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_16","first-page":"CD011776","article-title":"Symptomatic treatments for amyotrophic lateral sclerosis\/motor neuron disease","volume":"1","author":"Ng","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.neurol.2017.03.032","article-title":"Ethical considerations and palliative care in patients with amyotrophic lateral sclerosis: A review","volume":"173","author":"Touzet","year":"2017","journal-title":"Rev. Neurol."},{"key":"ref_18","first-page":"181","article-title":"Risk factors for amyotrophic lateral sclerosis","volume":"7","author":"Ingre","year":"2015","journal-title":"Clin. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.nrl.2015.12.001","article-title":"Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis","volume":"34","author":"Riancho","year":"2019","journal-title":"Neurologia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.gene.2015.11.049","article-title":"Mutant SOD1 mediated pathogenesis of Amyotrophic Lateral Sclerosis","volume":"577","author":"Kaur","year":"2016","journal-title":"Gene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nrneurol.2013.203","article-title":"The epidemiology of ALS: A conspiracy of genes, environment and time","volume":"9","author":"Hardiman","year":"2013","journal-title":"Nat. Rev. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fnmol.2019.00025","article-title":"Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis","volume":"12","author":"Prasad","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","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":"ref_24","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1212\/WNL.0b013e3181b6bbbd","article-title":"ALS motor phenotype heterogeneity, focality, and spread: Deconstructing motor neuron degeneration","volume":"73","author":"Ravits","year":"2009","journal-title":"Neurology"},{"key":"ref_25","first-page":"2084","article-title":"Amyotrophic lateral sclerosis","volume":"390","author":"Hardiman","year":"2018","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.neubiorev.2016.04.007","article-title":"Physical activity, and physical activity related to sports, leisure and occupational activity as risk factors for ALS: A systematic review","volume":"66","author":"Lacorte","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ibba, G., Piu, C., Uleri, E., Serra, C., and Dolei, A. (2018). Disruption by SaCas9 Endonuclease of HERV-Kenv, a Retroviral Gene with Oncogenic and Neuropathogenic Potential, Inhibits Molecules Involved in Cancer and Amyotrophic Lateral Sclerosis. Viruses, 10.","DOI":"10.3390\/v10080412"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Obrenovich, M., Jaworski, H., Tadimalla, T., Mistry, A., Sykes, L., Perry, G., and Bonomo, R.A. (2020). The Role of the Microbiota-Gut-Brain Axis and Antibiotics in ALS and Neurodegenerative Diseases. Microorganisms, 8.","DOI":"10.3390\/microorganisms8050784"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.4081\/ni.2011.e4","article-title":"Amyotrophic lateral sclerosis: One or multiple causes?","volume":"3","author":"Orsini","year":"2011","journal-title":"Neurol. Int."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Obrador, E., Salvador-Palmer, R., L\u00f3pez-Blanch, R., Jihad-Jebbar, A., Vall\u00e9s, S.L., and Estrela, J.M. (2021). The Link between Oxidative Stress, Redox Status, Bioenergetics and Mitochondria in the Pathophysiology of ALS. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126352"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1474-4422(12)70043-1","article-title":"Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: A cross-sectional study","volume":"11","author":"Majounie","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2527.e3","DOI":"10.1016\/j.neurobiolaging.2012.05.008","article-title":"UBQLN2\/ubiquilin 2 mutation and pathology in familial amyotrophic lateral sclerosis","volume":"33","author":"Williams","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1600-079X.2006.00377.x","article-title":"Reduced oxidative damage in ALS by high-dose enteral melatonin treatment","volume":"41","author":"Weishaupt","year":"2006","journal-title":"J. Pineal Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jbior.2015.10.006","article-title":"SOD1 in neurotoxicity and its controversial roles in SOD1 mutation-negative ALS","volume":"60","author":"Hayashi","year":"2016","journal-title":"Adv. Biol. Regul."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s12640-012-9337-4","article-title":"Melatonin antioxidative defense: Therapeutical implications for aging and neurodegenerative processes","volume":"23","author":"BaHammam","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature11280","article-title":"Mutations in the Profilin 1 Gene Cause Familial Amyotrophic Lateral Sclerosis","volume":"488","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.3390\/ijms13011225","article-title":"Disruption of axonal transport in motor neuron diseases","volume":"13","author":"Ikenaka","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.2174\/0929867321666140916120118","article-title":"The glutamate hypothesis in ALS: Pathophysiology and drug development","volume":"21","author":"Blasco","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Obrador, E., Salvador, R., Estrela, J.M., L\u00f3pez-Blanch, R., Jihad-Jebbar, A., and Vall\u00e9s, S.L. (2020). Oxidative Stress, Neuroinflammation and Mitochondria in the Pathophysiology of Amyotrophic Lateral Sclerosis. Antioxidants, 9.","DOI":"10.3390\/antiox9090901"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.2174\/092986710791163939","article-title":"Riluzole, neuroprotection and amyotrophic lateral sclerosis","volume":"17","author":"Cheah","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.brainres.2009.07.093","article-title":"Oxidative stress in immune-mediated motoneuron destruction","volume":"1302","author":"Xu","year":"2009","journal-title":"Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1172\/JCI42986","article-title":"Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis","volume":"120","author":"Reyes","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00401-018-1933-9","article-title":"Inflammation in ALS\/FTD pathogenesis","volume":"137","author":"McCauley","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_44","doi-asserted-by":"crossref","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":"ref_45","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/nbt.1957","article-title":"Astrocytes from Familial and Sporadic ALS Patients are Toxic to Motor Neurons","volume":"29","author":"Hester","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tarafdar, A., and Pula, G. (2018). The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123824"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1136\/jnnp-2017-317724","article-title":"Multicentre, cross-cultural, population-based, case-control study of physical activity as risk factor for amyotrophic lateral sclerosis","volume":"89","author":"Visser","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1136\/jnnp-2018-318147","article-title":"Physical activity as a risk factor in ALS","volume":"89","author":"Swash","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4231","DOI":"10.1007\/s10072-022-05990-4","article-title":"Common genetic basis of ALS patients and soccer players may contribute to disease risk","volume":"43","author":"Nefussy","year":"2022","journal-title":"Neurol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/epirev\/mxu001","article-title":"Military service, deployments, and exposures in relation to amyotrophic lateral sclerosis etiology and survival","volume":"37","author":"Beard","year":"2015","journal-title":"Epidemiol. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1136\/jnnp-2012-304724","article-title":"Lifetime physical activity and the risk of amyotrophic lateral sclerosis","volume":"84","author":"Huisman","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_52","first-page":"5021694","article-title":"Oxidative Stress in Amyotrophic Lateral Sclerosis: Pathophysiology and Opportunities for Pharmacological Intervention","volume":"2020","author":"Montezinho","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3109\/21678421.2016.1154575","article-title":"Long-term physical activity: An exogenous risk factor for sporadic amyotrophic lateral sclerosis?","volume":"17","author":"Harwood","year":"2016","journal-title":"Amyotroph. Lateral Scler. Front. Degener."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00401-017-1708-8","article-title":"Motor neuron vulnerability and resistance in amyotrophic lateral sclerosis","volume":"133","author":"Nijssen","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1159\/000089619","article-title":"Complexity of astrocyte-motor neuron interactions in amyotrophic lateral sclerosis","volume":"2","author":"Pehar","year":"2005","journal-title":"Neurodegener. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.chom.2020.06.008","article-title":"The Microbiome as a Modifier of Neurodegenerative Disease Risk","volume":"28","author":"Fang","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1002\/jcp.25518","article-title":"Neurotransmitters: The critical modulators regulating gut-brain axis","volume":"232","author":"Mittal","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.cub.2016.04.016","article-title":"Gut Microbiota and Extreme Longevity","volume":"26","author":"Biagi","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.immuni.2018.09.017","article-title":"Microbiota-Derived Lactate Activates Production of Reactive Oxygen Species by the Intestinal NADPH Oxidase Nox and Shortens Drosophila Lifespan","volume":"49","author":"Iatsenko","year":"2018","journal-title":"Immunity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1038\/s41467-019-10430-7","article-title":"Heterochronic faecal transplantation boosts gut germinal centres in aged mice","volume":"10","author":"Stebegg","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41586-019-1443-5","article-title":"Potential roles of gut microbiome and metabolites in modulating ALS in mice","volume":"572","author":"Blacher","year":"2019","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1080\/19490976.2020.1767464","article-title":"Amyotrophic lateral sclerosis and intestinal microbiota\u2014Toward establishing cause and effect","volume":"11","author":"Gotkine","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1996848","DOI":"10.1080\/19490976.2021.1996848","article-title":"Aberrant enteric neuromuscular system and dysbiosis in amyotrophic lateral sclerosis","volume":"13","author":"Zhang","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1001\/archneur.64.10.1388","article-title":"TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: Protein misfolding diseases without amyloidosis","volume":"64","author":"Neumann","year":"2007","journal-title":"Arch. Neurol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"240","DOI":"10.3109\/17482960902810890","article-title":"TDP-43 in skeletal muscle of patients affected with amyotrophic lateral sclerosis","volume":"11","author":"Orsetti","year":"2010","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/brain\/awab285","article-title":"Phosphorylated TDP-43 aggregates in peripheral motor nerves of patients with amyotrophic lateral sclerosis","volume":"145","author":"Riva","year":"2022","journal-title":"Brain"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/cjp2.297","article-title":"pTDP-43 aggregates accumulate in non-central nervous system tissues prior to symptom onset in amyotrophic lateral sclerosis: A case series linking archival surgical biopsies with clinical phenotypic data","volume":"9","author":"Pattle","year":"2023","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"117864691877665","DOI":"10.1177\/1178646918776658","article-title":"The Influence of Nicotinamide on Health and Disease in the Central Nervous System","volume":"11","author":"Fricker","year":"2018","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nn.4476","article-title":"Interactions between the microbiota, immune and nervous systems in health and disease","volume":"20","author":"Fung","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"839526","DOI":"10.3389\/fcimb.2022.839526","article-title":"A Gut Feeling in Amyotrophic Lateral Sclerosis: Microbiome of Mice and Men","volume":"12","author":"Martin","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.3389\/fimmu.2017.01005","article-title":"Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications","volume":"8","author":"Liu","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s00401-018-1856-5","article-title":"Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: A common path to neurodegenerative diseases?","volume":"136","author":"Pellegrini","year":"2018","journal-title":"Acta Neuropathol."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/45\/4\/217\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:12:18Z","timestamp":1760123538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/45\/4\/217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,7]]},"references-count":72,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["cimb45040217"],"URL":"https:\/\/doi.org\/10.3390\/cimb45040217","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,7]]}}}