{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T21:36:59Z","timestamp":1770413819999,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Technology R&D Project through the Korea Health Industry Development Institute"},{"name":"Ministry of Health & Welfare, Republic of Korea","award":["HI22C2064"],"award-info":[{"award-number":["HI22C2064"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>While phosphatidylserine (PS) is recognized for its neuroprotective properties, the effects of PS purity on human cortical neurons remain unexplored. This study investigates the effects of three different PS purities (15 \u00b5M of 50%, 70%, and 80%) on neuronal health using human-embryonic-stem-cell-derived cortical neurons. Our findings reveal that higher PS purity enhances the expression of key regulatory proteins Sirtuin 1 (SIRT1) and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1\u03b1), known for their roles in neuroprotection and mitochondrial function. Specifically, 80% PS purity significantly increases SIRT1 and PGC-1\u03b1 levels, suggesting that PS purity strengthens neuroprotective pathways and improves mitochondrial quality control. Through SIRT1 knockdown experiments, we demonstrate that PS-induced upregulation of PGC-1\u03b1 is SIRT1 dependent, highlighting a SIRT1-PGC-1\u03b1 regulatory axis that enhances mitochondrial health. In an amyloid-beta 1\u201342 (A\u03b242)-induced Alzheimer\u2019s disease (AD) model, PS treatment reduced cytotoxicity and countered the A\u03b242-induced downregulation of SIRT1 and PGC-1\u03b1, particularly at 70% and 80% PS purity, indicating PS\u2019s role in preserving neuronal viability and combating AD-like pathology. These results suggest that the biological activity of PS preparations in vitro can depend on purity, motivating future studies to define compositional determinants and bioavailability relevant to translational applications.<\/jats:p>","DOI":"10.3390\/brainsci16020194","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:05:47Z","timestamp":1770372347000},"page":"194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Higher Purity of Phosphatidylserine Improves Human Cortical Neuron Function by Modulating SIRT1-PGC-1\u03b1 Pathways"],"prefix":"10.3390","volume":"16","author":[{"given":"Sung-Min","family":"Jeon","sequence":"first","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon-Seob","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dentistry, College of Dentistry, Yonsei University, Seoul 03722, Republic of Korea"},{"name":"The Yonsei Dental Clinic, Suwon 16385, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Yu","family":"Lee","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eunice J.","family":"Kang","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommy D.","family":"Kim","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayna","family":"Shin","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4170-945X","authenticated-orcid":false,"given":"Heejin","family":"Jo","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"},{"name":"Department of Korean Medicine, School of Medicine, CHA University, Seoul 06062, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8393-2588","authenticated-orcid":false,"given":"Sung-Ung","family":"Kang","sequence":"additional","affiliation":[{"name":"Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"},{"name":"Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/eva.12187","article-title":"Costs of antibiotic resistance\u2014Separating trait effects and selective effects","volume":"8","author":"Hall","year":"2015","journal-title":"Evol. Appl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13014-020-01489-4","article-title":"Where is clinical research for radiotherapy going? Cross-sectional comparison of past and contemporary phase III clinical trials","volume":"15","author":"Park","year":"2020","journal-title":"Radiat. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.1016\/j.bmcl.2010.06.132","article-title":"Synthesis, in vitro and in vivo evaluation of 3-arylisoquinolinamines as potent antitumor agents","volume":"20","author":"Yang","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/j.jmir.2019.06.052","article-title":"Future Vistas in Alpha Therapy of Infectious Diseases","volume":"50","author":"Dadachova","year":"2019","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1124\/jpet.105.084145","article-title":"Role of tyrosine kinase inhibitors in cancer therapy","volume":"315","author":"Arora","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1038\/s41467-020-19982-5","article-title":"Sound generation in zebrafish with Bio-Opto-Acoustics","volume":"11","author":"Taylor","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"346ra90","DOI":"10.1126\/scitranslmed.aad8335","article-title":"Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage","volume":"8","author":"Heinemeier","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"ajpe8600","DOI":"10.5688\/ajpe8600","article-title":"Predictors of Academic Success in a Nontraditional Doctor of Pharmacy Degree Program at a Historically Black College and University","volume":"86","author":"Karodeh","year":"2022","journal-title":"Am. J. Pharm. Educ."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hashimoto, Y., Zhang, S., and Blissard, G.W. (2010). Ao38, a new cell line from eggs of the black witch moth, Ascalapha odorata (Lepidoptera: Noctuidae), is permissive for AcMNPV infection and produces high levels of recombinant proteins. BMC Biotechnol., 10.","DOI":"10.1186\/1472-6750-10-50"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ophtha.2020.07.015","article-title":"Visual and Patient-Reported Outcomes of a Diffractive Trifocal Intraocular Lens Compared with Those of a Monofocal Intraocular Lens","volume":"128","author":"Modi","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.eurpsy.2011.05.004","article-title":"The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: A double-blind placebo-controlled trial, followed by an open-label extension","volume":"27","author":"Manor","year":"2012","journal-title":"Eur. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/j.ejso.2021.04.012","article-title":"Concerning CT features predict outcome of treatment in patients with malignant peritoneal mesothelioma","volume":"47","author":"Sugarbaker","year":"2021","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1002\/hbm.25702","article-title":"Dysregulated anterior insula reactivity as robust functional biomarker for chronic pain-Meta-analytic evidence from neuroimaging studies","volume":"43","author":"Ferraro","year":"2022","journal-title":"Hum. Brain Mapp."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.jcis.2022.04.154","article-title":"Dual-Carbon confinement strategy of antimony anode material enabling advanced potassium ion storage","volume":"622","author":"Zheng","year":"2022","journal-title":"J. Colloid Interface Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.01928-20","article-title":"Antiviral Activity of Type I, II, and III Interferons Counterbalances ACE2 Inducibility and Restricts SARS-CoV-2","volume":"11","author":"Busnadiego","year":"2020","journal-title":"mBio"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1056\/NEJMoa030656","article-title":"The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia","volume":"349","author":"McConnell","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1242\/dev.02655","article-title":"The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25","volume":"133","author":"Hayes","year":"2006","journal-title":"Development"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/s41588-021-00923-x","article-title":"Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation","volume":"53","author":"Min","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"166207","DOI":"10.1016\/j.bbadis.2021.166207","article-title":"Growth impairment, increased placental glucose uptake and altered transplacental transport in VIP deficient pregnancies: Maternal vs. placental contributions","volume":"1867","author":"Merech","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/ncb1442","article-title":"Critical role for Daxx in regulating Mdm2","volume":"8","author":"Tang","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21620","DOI":"10.1038\/s41598-020-77550-9","article-title":"Computational modeling of human reasoning processes for interpretable visual knowledge: A case study with radiographers","volume":"10","author":"Li","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1044\/1092-4388(2010\/09-0100)","article-title":"Effects of noise and speech intelligibility on listener comprehension and processing time of Korean-accented English","volume":"53","author":"Wilson","year":"2010","journal-title":"J. Speech Lang. Hear. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jvs.2011.10.122","article-title":"Mesenteric artery complications during angioplasty and stent placement for atherosclerotic chronic mesenteric ischemia","volume":"55","author":"Oderich","year":"2012","journal-title":"J. Vasc. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JB.00052-21","article-title":"Behind the shield of Czc: ZntR controls expression of the gene for the zinc-exporting P-type ATPase ZntA in Cupriavidus metallidurans","volume":"203","author":"Schulz","year":"2021","journal-title":"J. Bacteriol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4440","DOI":"10.1038\/s41467-021-24576-w","article-title":"Ageing is associated with disrupted reinforcement learning whilst learning to help others is preserved","volume":"12","author":"Cutler","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4827","DOI":"10.1091\/mbc.e05-04-0315","article-title":"Active Nercc1 protein kinase concentrates at centrosomes early in mitosis and is necessary for proper spindle assembly","volume":"16","author":"Roig","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ijbiomac.2022.01.050","article-title":"Serum albumin as a primary non-covalent binding protein for nitro-oleic acid","volume":"203","author":"Hernychova","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1021\/am400374c","article-title":"MicroRNA functionalized microporous titanium oxide surface by lyophilization with enhanced osteogenic activity","volume":"5","author":"Wu","year":"2013","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/cpim.43","article-title":"Liposome Preparation for the Analysis of Lipid-Receptor Interaction and Efferocytosis","volume":"120","author":"Voss","year":"2018","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00706-022-02966-0","article-title":"Liposomes: Preparation and characterization with a special focus on the application of capillary electrophoresis","volume":"153","author":"Tomnikova","year":"2022","journal-title":"Monatsh. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"333ra48","DOI":"10.1126\/scitranslmed.aad0623","article-title":"Cultured networks of excitatory projection neurons and inhibitory interneurons for studying human cortical neurotoxicity","volume":"8","author":"Xu","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jneumeth.2010.05.001","article-title":"An improved method for generating consistent soluble amyloid-beta oligomer preparations for in vitro neurotoxicity studies","volume":"190","author":"Ryan","year":"2010","journal-title":"J. Neurosci. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fa, M., Orozco, I.J., Francis, Y.I., Saeed, F., Gong, Y., and Arancio, O. (2010). Preparation of oligomeric beta-amyloid1-42 and induction of synaptic plasticity impairment on hippocampal slices. J. Vis. Exp., 1884.","DOI":"10.3791\/1884"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.7150\/thno.105953","article-title":"Pharmacological targeting of mitophagy via ALT001 improves herpes simplex virus 1 (HSV1)-mediated microglial inflammation and promotes amyloid beta phagocytosis by restricting HSV1 infection","volume":"15","author":"Oh","year":"2025","journal-title":"Theranostics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s13287-025-04324-3","article-title":"Extracellular vesicles from hiPSC-derived NSCs protect human neurons against Abeta-42 oligomers induced neurodegeneration, mitochondrial dysfunction and tau phosphorylation","volume":"16","author":"Rao","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_36","first-page":"e70040","article-title":"Anticholinergic drugs and dementia risk: Using stem cell-based studies to complement pharmacoepidemiology","volume":"11","author":"Pranoto","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1677\/JME-07-0043","article-title":"Role of specificity protein transcription factors in estrogen-induced gene expression in MCF-7 breast cancer cells","volume":"39","author":"Khan","year":"2007","journal-title":"J. Mol. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/ENEURO.0148-19.2019","article-title":"Neurons Derived from Human Induced Pluripotent Stem Cells Integrate into Rat Brain Circuits and Maintain Both Excitatory and Inhibitory Synaptic Activities","volume":"6","author":"Yin","year":"2019","journal-title":"eNeuro"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1002\/stem.514","article-title":"Functional control of transplantable human ESC-derived neurons via optogenetic targeting","volume":"28","author":"Weick","year":"2010","journal-title":"Stem Cells"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e70657","DOI":"10.1111\/cns.70657","article-title":"AMPK\/SIRT1\/PGC-1alpha Signaling Pathway: Molecular Mechanisms and Targeted Strategies From Energy Homeostasis Regulation to Disease Therapy","volume":"31","author":"Chen","year":"2025","journal-title":"CNS Neurosci. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"102713","DOI":"10.1016\/j.arr.2025.102713","article-title":"Mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"107","author":"Kanaan","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e00525","DOI":"10.1016\/j.neurot.2025.e00525","article-title":"Mitochondrial dysfunction in Alzheimer\u2019s disease: Guiding the path to targeted therapies","volume":"22","author":"Liu","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tang, M.B., Liu, Y.X., Hu, Z.W., Luo, H.Y., Zhang, S., Shi, C.H., and Xu, Y.M. (2024). Study insights in the role of PGC-1alpha in neurological diseases: Mechanisms and therapeutic potential. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1454735"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e105380","DOI":"10.15252\/embj.2020105380","article-title":"Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia","volume":"39","author":"Perrucci","year":"2020","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/j.1471-4159.1989.tb07358.x","article-title":"Uptake of exogenous phosphatidylserine by human neuroblastoma cells stimulates the incorporation of [methyl-14C]choline into phosphatidylcholine","volume":"53","author":"Slack","year":"1989","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/lipd.12269","article-title":"Lipid Composition of Liposomal Membrane Largely Affects Its Transport and Uptake through Small Intestinal Epithelial Cell Models","volume":"55","author":"Konishi","year":"2020","journal-title":"Lipids"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ma, X., Li, X., Wang, W., Zhang, M., Yang, B., and Miao, Z. (2022). Phosphatidylserine, inflammation, and central nervous system diseases. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.975176"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.freeradbiomed.2014.07.029","article-title":"AMPK activation prevents prenatal stress-induced cognitive impairment: Modulation of mitochondrial content and oxidative stress","volume":"75","author":"Cao","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1091\/mbc.e11-11-0936","article-title":"Phosphatidylserine dynamics in cellular membranes","volume":"23","author":"Kay","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/jnc.14886","article-title":"Phosphatidylserine is critical for vesicle fission during clathrin-mediated endocytosis","volume":"152","author":"Varga","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Panes, J.D., Godoy, P.A., Silva-Grecchi, T., Celis, M.T., Ramirez-Molina, O., Gavilan, J., Mu\u00f1oz-Montecino, C., Castro, P.A., Moraga-Cid, G., and Y\u00e9venes, G.E. (2020). Changes in PGC-1alpha\/SIRT1 Signaling Impact on Mitochondrial Homeostasis in Amyloid-Beta Peptide Toxicity Model. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00709"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jad.2024.09.131","article-title":"Effects of a food supplement containing phosphatidylserine on cognitive function in Chinese older adults with mild cognitive impairment: A randomized double-blind, placebo-controlled trial","volume":"369","author":"Duan","year":"2025","journal-title":"J. Affect. Disord."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6128","DOI":"10.18632\/oncotarget.23640","article-title":"Drp1\/Fis1 interaction mediates mitochondrial dysfunction, bioenergetic failure and cognitive decline in Alzheimer\u2019s disease","volume":"9","author":"Joshi","year":"2018","journal-title":"Oncotarget"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1093\/hmg\/ddr139","article-title":"Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer\u2019s disease: Implications for neuronal damage","volume":"20","author":"Manczak","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0092-8674(00)80611-X","article-title":"Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1","volume":"98","author":"Wu","year":"1999","journal-title":"Cell"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/2\/194\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:28:50Z","timestamp":1770373730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/2\/194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":55,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["brainsci16020194"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16020194","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}