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Here, we exposed human iPSC-derived midbrain DA organoids and differentiated SH-SY5Y neurons to simulated microgravity for 72 hours. This exposure reduced neurite outgrowth, eroded DA identity, and activated familial-PD mitochondrial kinases without depleting extracellular dopamine. We observed severe mitochondrial dysfunction\u2014including membrane potential loss and respiratory suppression\u2014coupled with global translational repression. Furthermore, a sublethal, pre-degenerative state emerged, characterized by the selective release of mitochondrial cell-free DNA without apoptotic activation. Proteomic profiling revealed striking convergence with human PD transcriptomes and astronaut blood, highlighting shared suppression of mitochondrial metabolism, ribosomal translation, and altered RNA splicing. Together, these findings establish simulated microgravity as a sufficient, non-toxin trigger of early PD-like DA dysfunction, providing a robust human model for investigating prodromal neurodegeneration.<\/jats:p>","DOI":"10.64898\/2026.07.09.737494","type":"posted-content","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:55:16Z","timestamp":1784181316000},"source":"Crossref","is-referenced-by-count":3,"title":["Spaceflight-relevant microgravity triggers a sublethal Parkinson\u2019s-like dopaminergic decline in human neurons and organoids"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-0821","authenticated-orcid":false,"given":"Nilufar","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shehbeel","family":"Arif","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max-Florian","family":"Mortimer","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Brandner","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Baldridge","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben Ferreira","family":"Paiva","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukta S.","family":"Sane","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"},{"name":"Biomolecular Research Centre, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Woodbury","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"},{"name":"Biomolecular Research Centre, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunes","family":"Uzer","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Biomedical Engineering, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Jorcyk","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Hampikian","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"},{"name":"CompGenomics, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masihhur","family":"Laskar","sequence":"additional","affiliation":[{"name":"SpinAxis Biosystem, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Oxford","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Boise State University, Boise, ID, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071801251431000_2026.07.09.737494v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30295-3"},{"key":"2026071801251431000_2026.07.09.737494v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00218-X"},{"key":"2026071801251431000_2026.07.09.737494v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30230-7"},{"key":"2026071801251431000_2026.07.09.737494v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.039"},{"key":"2026071801251431000_2026.07.09.737494v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"2026071801251431000_2026.07.09.737494v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61393-3"},{"key":"2026071801251431000_2026.07.09.737494v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41526-024-00457-6"},{"key":"2026071801251431000_2026.07.09.737494v1.8","unstructured":"Trovao, N. 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