{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:15:22Z","timestamp":1790262922985,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"publisher","award":["AARF-22-967198"],"award-info":[{"award-number":["AARF-22-967198"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"award":["AARF-22-967198"],"award-info":[{"award-number":["AARF-22-967198"]}],"id":[{"id":"https:\/\/ror.org\/0375f4d26","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Research Manitoba award","award":["1913"],"award-info":[{"award-number":["1913"]}]},{"name":"St. Boniface Hospital Research Foundation","award":["1406\u20133216"],"award-info":[{"award-number":["1406\u20133216"]}]},{"name":"St. Boniface Hospital Research Foundation","award":["1410\u20133216"],"award-info":[{"award-number":["1410\u20133216"]}]},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","award":["PJT-162144"],"award-info":[{"award-number":["PJT-162144"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PJT-162144"],"award-info":[{"award-number":["PJT-162144"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"name":"NIH R16","award":["1R16NS134540-01"],"award-info":[{"award-number":["1R16NS134540-01"]}]},{"name":"Alzheimer\u2019s Society of Manitoba","award":["1403\u20133131"],"award-info":[{"award-number":["1403\u20133131"]}]},{"award":["1403\u20133131"],"award-info":[{"award-number":["1403\u20133131"]}],"id":[{"id":"https:\/\/ror.org\/05ef6s903","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is characterized by the accumulation of amyloid beta (A\u03b2) and neurofibrillary tangles in brain tissue; however, AD is multifactorial, and different etiopathogenic mechanisms involve factors that can affect mitochondrial function, which are associated with AD. While high-dose lithium is a well-established mood stabilizer, accumulating evidence suggests that low-dose lithium provides significant neuroprotection by reversing AD pathology, cognitive impairment, and inflammation. Despite these findings, there is limited information on how lithium affects brain energy metabolism. In the current study, we investigated the effect of lithium (0, 0.1, 1, and 10 mM) on mitochondrial function in AD neurons. Neuronal cells were isolated from the hippocampi of embryonic day 14\u201317 (E15\u2013E17) control (C57BL\/6) mice and 3xTg-AD mice. Mitochondrial oxygen consumption rate (OCR), mitochondrial Cytochrome C Oxidase (COX) activity, total ATP activity, and the expression of mitochondrial complex protein involved in oxidative phosphorylation (OXPHOS) were measured in control vs. 3xTg-AD in the presence and absence of lithium treatment. In the present study, lithium treatment significantly increased (p &lt; 0.05) mitochondrial OCR, COX, total ATP, and levels of mitochondrial complex protein subunits (Complex I\u2013V) in 3xTg-AD neurons. However, lithium had no effect on energy metabolism in control neurons. Together, these data indicate that lithium improves mitochondrial function under pathological states. Overall, these results have important implications for the treatment of disorders in which brain energy regulation is compromised, including AD. Particularly, our results highlight a role for lithium in regulating bioenergetics in early-stage AD and suggest that neuronal cells may be a crucial therapeutic target for preventing AD.<\/jats:p>","DOI":"10.3390\/cells15100896","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:06:26Z","timestamp":1779696386000},"page":"896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Mitochondrial Dysfunction in Alzheimer\u2019s Disease Neurons: Lithium Boosts Oxidative Phosphorylation"],"prefix":"10.3390","volume":"15","author":[{"given":"Benedict C.","family":"Albensi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Barry & Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA"},{"name":"Division of Neurodegenerative Disorders, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada"},{"name":"Department of Pharmacology & Therapeutics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0T6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Adlimoghaddam","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dale and Deborah Smith Center for Alzheimer\u2019s Research and Treatment, Neuroscience Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, USA"},{"name":"Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA"},{"name":"Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1001\/jamaneurol.2013.5847","article-title":"Amyloid-beta and tau: The trigger and bullet in Alzheimer disease pathogenesis","volume":"71","author":"Bloom","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41392-023-01484-7","article-title":"Amyloid beta-based therapy for Alzheimer\u2019s disease: Challenges, successes and future","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. 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