{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T23:23:00Z","timestamp":1784848980361,"version":"3.55.0"},"reference-count":103,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008483","name":"NOMIS Stiftung","doi-asserted-by":"publisher","award":["na"],"award-info":[{"award-number":["na"]}],"id":[{"id":"10.13039\/501100008483","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helmholtz Virtual Institute \u201cRNA dysmetabolism in ALS and FTD&quot;","award":["VH-VI-510"],"award-info":[{"award-number":["VH-VI-510"]}]},{"name":"Hermann und Lilly Schilling-Stiftung f\u00fcr medizinische Forschung im Stifterverband","award":["na"],"award-info":[{"award-number":["na"]}]},{"name":"Else-Kr\u00f6ner-Fresenius-Stiftung","award":["na"],"award-info":[{"award-number":["na"]}]},{"DOI":"10.13039\/501100010275","name":"Deutsche Gesellschaft f\u00fcr Muskelkranke","doi-asserted-by":"publisher","award":["He2\/2"],"award-info":[{"award-number":["He2\/2"]}],"id":[{"id":"10.13039\/501100010275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotropic lateral sclerosis (ALS) is a lethally progressive and irreversible neurodegenerative disease marked by apparent death of motor neurons present in the spinal cord, brain stem and motor cortex. While more and more gene mutants being established for genetic ALS, the vast majority suffer from sporadic ALS (&gt;90%). It has been challenging, thus, to model sporadic ALS which is one reason why the underlying pathophysiology remains elusive and has stalled the development of therapeutic strategies of this progressive motor neuron disease. To further unravel these pathological signaling pathways, human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs) from FUS- and SOD1 ALS patients and healthy controls were systematically compared to independent published datasets. Here through this study we created a gene profile of ALS by analyzing the DEGs, the Kyoto encyclopedia of Genes and Genomes (KEGG) pathways, the interactome and the transcription factor profiles (TF) that would identify altered molecular\/functional signatures and their interactions at both transcriptional (mRNAs) and translational levels (hub proteins and TFs). Our findings suggest that FUS and SOD1 may develop from dysregulation in several unique pathways and herpes simplex virus (HSV) infection was among the topmost predominant cellular pathways connected to FUS and not to SOD1. In contrast, SOD1 is mainly characterized by alterations in the metabolic pathways and alterations in the neuroactive-ligand\u2013receptor interactions. This suggests that different genetic ALS forms are singular diseases rather than part of a common spectrum. This is important for patient stratification clearly pointing towards the need for individualized medicine approaches in ALS.<\/jats:p>","DOI":"10.3390\/ijms21186938","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T21:01:21Z","timestamp":1600722081000},"page":"6938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Genome Wide Analysis Points towards Subtype-Specific Diseases in Different Genetic Forms of Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4580-139X","authenticated-orcid":false,"given":"Banaja P.","family":"Dash","sequence":"first","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht-Kossel\u201d, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Naumann","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht-Kossel\u201d, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Sterneckert","sequence":"additional","affiliation":[{"name":"Center for Regenerative Therapies Dresden (CRTD), Technische Universit\u00e4t Dresden, 01069 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7364-7791","authenticated-orcid":false,"given":"Andreas","family":"Hermann","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht-Kossel\u201d, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE) Rostock\/Greifswald, 18147 Rostock, Germany"},{"name":"Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/S0140-6736(10)61156-7","article-title":"Amyotrophic lateral sclerosis","volume":"377","author":"Kiernan","year":"2011","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1007\/s00415-016-8091-6","article-title":"Recent advances in amyotrophic lateral sclerosis","volume":"263","author":"Riva","year":"2016","journal-title":"J. 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