{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:42:31Z","timestamp":1793745751400,"version":"4.6.1"},"reference-count":79,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014076","name":"Stichting ALS Nederland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting upper and lower motor neurons leading to muscle wasting. However, structural and molecular abnormalities, including cortical thinning and TDP\u201043 pathology, extend into frontal, parietal, and temporal areas, pointing to defects across broader cortical regions. The advent of human induced pluripotent stem cell (hiPSC) technology has enabled the generation of human\u2010specific brain cell types in\u00a0vitro. Here, we provide an overview of the three\u2010dimensional (3D) hiPSC\u2010derived neural organoid platforms used to model cortical structures and to study cortical ALS\u2010associated phenotypes. We review which pathological hallmarks have been recapitulated in these organoids and discuss disease phenotypes reported to date. Further, we comprehensively cover different neural organoid models and experimental strategies, including patient\u2010derived hiPSC models and exogenous pathology induction, while addressing current technical challenges. Together, these advances position neural organoids as an emerging tool to study cell\u2010type\u2010specific and circuit\u2010level mechanisms related to cortical changes in ALS.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70513-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70513","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:02:51Z","timestamp":1782907371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neural Organoid Models as a Platform for Studying Disease Mechanisms in Amyotrophic Lateral Sclerosis"],"prefix":"10.1111","volume":"170","author":[{"given":"Kristel N.","family":"Eigenhuis","sequence":"first","affiliation":[{"name":"Department of Translational Neuroscience University Medical Center Utrecht  Utrecht CG the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto Montoro","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience University Medical Center Utrecht  Utrecht CG the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Jeroen","family":"Pasterkamp","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience University Medical Center Utrecht  Utrecht CG the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00592-y"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.203"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.017"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07578-8"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0238-7"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4304"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0047-2"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00479-4"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22330"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2660"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.221"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23937"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04436-3"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.115057"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","unstructured":"Chin N. 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