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Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by the loss of motoneurons, with a complex etiology, combining genetic, epigenetic, and environmental causes. The neuroprotective therapeutic approaches are very limited, while the diagnostics rely on clinical examination and the exclusion of other diseases. The recent advancement in the discovery of molecular pathways and gene mutations involved in ALS has deepened the understanding of the disease pathology and opened the possibility for new treatments and diagnostic procedures. Recently, 15 risk loci with distinct genetic architectures and neuron-specific biology were identified as linked to ALS through common and rare variant association analyses. Interestingly, the quantity of related proteins to these genes has been found to change during early postnatal development in mammalian spinal cord tissue (opossum Monodelphis domestica) at the particular time when neuroregeneration stops being possible. Here, we discuss the possibility that the ALS-related genes\/proteins could be connected to neuroregeneration and development. Moreover, since the regulation of gene expression in developmental checkpoints is frequently regulated by non-coding RNAs, we propose that studying the changes in the composition and quantity of non-coding RNA molecules, both in ALS patients and in the developing central nervous (CNS) system of the opossum at the time when neuroregeneration ceases, could reveal potential biomarkers useful in ALS prognosis and diagnosis.<\/jats:p>","DOI":"10.3390\/ijms231911360","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T23:12:12Z","timestamp":1664320332000},"page":"11360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Potential Connection between Molecular Changes and Biomarkers Related to ALS and the Development and Regeneration of CNS"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9912-3331","authenticated-orcid":false,"given":"Damjan","family":"Glava\u010d","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljublana, Slovenia"},{"name":"Center for Human Genetics & Pharmacogenomics, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3985-6629","authenticated-orcid":false,"given":"Miranda","family":"Mladini\u0107","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neurobiology, Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5792-3998","authenticated-orcid":false,"given":"Jelena","family":"Ban","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neurobiology, Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graciela L.","family":"Mazzone","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional (IIMT), CONICET-Universidad Austral, Buenos Aires B1629AHJ, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-9582","authenticated-orcid":false,"given":"Cynthia","family":"S\u00e1mano","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Naturales, Universidad Aut\u00f3noma Metropolitana Unidad Cuajimalpa, Mexico City 05348, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Tomljanovi\u0107","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neurobiology, Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-5345","authenticated-orcid":false,"given":"Gregor","family":"Jezernik","sequence":"additional","affiliation":[{"name":"Center for Human Genetics & Pharmacogenomics, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-4215","authenticated-orcid":false,"given":"Metka","family":"Ravnik-Glava\u010d","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S1474-4422(18)30394-6","article-title":"Immune dysregulation in amyotrophic lateral sclerosis: Mechanisms and emerging therapies","volume":"18","author":"Beers","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1136\/bmj.318.7191.1118","article-title":"Motor Neurone Disease","volume":"318","author":"Shaw","year":"1999","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neuron.2006.09.018","article-title":"ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors","volume":"52","author":"Velde","year":"2006","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1002\/ana.21543","article-title":"Current hypotheses for the underlying biology of amyotrophic lateral sclerosis","volume":"65","author":"Rothstein","year":"2009","journal-title":"Ann. 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