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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is increasingly recognized as a disorder involving profound mitochondrial dysfunction. Although photobiomodulation (PBM) has shown neuroprotective efficacy in experimental AD models, whether restoration of mitochondrial architecture is mechanistically required for these effects remains unknown. Here, we investigated the role of mitochondrial network remodeling in PBM-mediated neuroprotection in primary mouse hippocampal neurons exposed to amyloid-\u03b2 (A\u03b2). Neurons were treated for 24 h with oligomeric A\u03b21\u201342 and irradiated with 808 nm PBM (100 mW\/cm2, 30 J\/cm2). Mitochondrial morphology was quantified using three-dimensional confocal microscopy and computational network analysis. A\u03b2 exposure induced severe mitochondrial fragmentation and swelling, reflected by increased mitochondrial count and sphericity together with reduced mitochondrial volume, surface area, branch length, and network connectivity. These structural alterations were accompanied by elevated reactive oxygen species production, adenosine triphosphate depletion, membrane depolarization, and reduced neuronal viability. PBM significantly reversed these abnormalities, restoring mitochondrial network integrity and partially normalizing cellular bioenergetics and redox homeostasis. To determine whether mitochondrial dynamics contributes to PBM-induced effects, neurons in another experiment were pre-treated with the dynamin-related protein-1 (DRP-1) mitochondrial division inhibitor-1 (Mdivi-1). The physiological and morphological profiles of the A\u03b2 + PBM + Mdivi-1 and A\u03b2 + Mdivi-1 groups were found to be largely indistinguishable in this case, revealing that PBM failed to restore mitochondrial connectivity, cellular bioenergetics, or viability of neurons in the partially blocked fission\u2013fusion machinery. These findings demonstrate that mitochondrial dynamics is essential for PBM-mediated neuroprotection and identify restoration of mitochondrial network integrity as a crucial mechanism linking PBM to improved neuronal bioenergetics, redox balance, and survival in AD.<\/jats:p>","DOI":"10.3390\/ijms27177834","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:08:43Z","timestamp":1788275323000},"page":"7834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Photobiomodulation with 808 nm Laser Light Repairs Mitochondrial Integrity and Normalizes ROS, ATP, and Membrane Depolarization in A\u03b2-Exposed Primary Neurons in Alzheimer\u2019s Disease Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3916-6588","authenticated-orcid":false,"given":"Iuliia","family":"Golovynska","sequence":"first","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Binjun","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8706-107X","authenticated-orcid":false,"given":"Qinglin","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1864-976X","authenticated-orcid":false,"given":"Sergii","family":"Golovynskyi","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6349-631X","authenticated-orcid":false,"given":"Yurii V.","family":"Stepanov","sequence":"additional","affiliation":[{"name":"R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Science of Ukraine, 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Liudmyla I.","family":"Stepanova","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, 01601 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Fangrui","family":"Lin","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7833-4711","authenticated-orcid":false,"given":"Junle","family":"Qu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7051-6534","authenticated-orcid":false,"given":"Tymish Y.","family":"Ohulchanskyy","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Photonics and Biophotonics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"d\u2018Errico, P., and Meyer-Luehmann, M. 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