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Biosci. (Elite Ed)"],"abstract":"<jats:p>Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder with which the leucine-Rich repeat kinase 2 glycine 2019 serine (LRRK2 G2019S) mutation is strongly associated. This mutation elevates kinase activity, disrupts mitochondrial function, increases reactive oxygen species (ROS) production, and impairs DNA repair mechanisms, all of which contribute to the pathogenesis of PD. Thus, addressing these pathological features through targeted delivery systems holds promise for more effective therapies. Methods: This study aimed to investigate the use of Ginkgo biloba leaf extract (EGB) to synthesize sphingomyelin-cholesterol solid lipid nanoparticles (SLNPs) functionalized with poly-L-lysine (EGB\u2013PLL\u2013SLNPs) for siRNA delivery targeting the LRRK2 G2019S mutation. SLNPs suspended in water (H\u2082O\u2013PLL\u2013SLNPs) served as the comparator. In vitro assays were conducted using either wild-type or LRRK2 G2019S-transformed SH-SY5Y and HEK293 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to evaluate the cytotoxicity of the SLNPs and nanocomplexes; meanwhile, flow cytometry was used to assess caspase 3\/7 activity, mitochondrial membrane potential, DNA damage, and ROS levels. Results: Treatment with EGB\u2013PLL\u2013SLNPs significantly improved mitochondrial health, reducing depolarized and dead cells and enhancing overall cell viability. ROS levels, DNA damage and kinase activity were significantly decreased compared to the control H\u2082O\u2013PLL\u2013SLNPs. Conclusion: The enhanced therapeutic outcomes observed with the EGB\u2013PLL\u2013SLNPs can be attributed to the bioactive compounds in EGB, particularly the flavonoids and terpenoids, such as quercetin and kaempferol. These molecules play crucial roles in stabilizing mitochondrial membranes, facilitating ATP synthesis, and regulating genes linked to mitochondrial biogenesis. The interaction between EGB and siRNA to mediate gene silencing provides a multifaceted approach to counteracting PD pathophysiology. This study demonstrates that EGB\u2013PLL\u2013SLNPs offer superior gene silencing and cytoprotective effects compared to conventional formulations. The integration of plant-based bioactives with nanomedicine enhances therapeutic delivery and efficacy, positioning biosynthesized PLL\u2013SLNPs as a promising strategy for treating Parkinson's disease.<\/jats:p>","DOI":"10.31083\/fbe44344","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:51:16Z","timestamp":1767181876000},"source":"Crossref","is-referenced-by-count":2,"title":["Targeting the LRRK2 G2019S Mutation Found in Parkinson's Disease: Efficiency of Biosynthesized Solid Lipid Nanoparticles for Therapeutic siRNA-Mediated Gene Therapy"],"prefix":"10.31083","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-1596","authenticated-orcid":true,"given":"Keelan","family":"Jagaran","sequence":"first","affiliation":[{"name":"Nano-Gene and Drug Delivery Laboratory, Discipline of Biochemistry, University of KwaZulu-Natal, 4000 Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9985-6567","authenticated-orcid":true,"given":"Moganavelli","family":"Singh","sequence":"additional","affiliation":[{"name":"Nano-Gene and Drug Delivery Laboratory, Discipline of Biochemistry, University of KwaZulu-Natal, 4000 Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Virreira Winter S, Karayel O, Strauss MT, Padmanabhan S, Surface M, Merchant K, et al. Urinary proteome profiling for stratifying patients with familial Parkinson\u2019s disease. EMBO Molecular Medicine. 2021; 13: e13257.","DOI":"10.15252\/emmm.202013257"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Przedborski S. The two-century journey of Parkinson disease research. Nature Reviews. Neuroscience. 2017; 18: 251\u2013259.","DOI":"10.1038\/nrn.2017.25"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Schapira AHV, Chaudhuri KR, Jenner P. Non-motor features of Parkinson disease. Nature Reviews. Neuroscience. 2017; 18: 435\u2013450.","DOI":"10.1038\/nrn.2017.62"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Deng H, Wang P, Jankovic J. The genetics of Parkinson disease. Ageing Research Reviews. 2018; 42: 72\u201385.","DOI":"10.1016\/j.arr.2017.12.007"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Walter J, Bolognin S, Poovathingal SK, Magni S, G\u00e9rard D, Antony PMA, et al. The Parkinson\u2019s-disease-associated mutation LRRK2-G2019S alters dopaminergic differentiation dynamics via NR2F1. Cell Reports. 2021; 37: 109864.","DOI":"10.1016\/j.celrep.2021.109864"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Croce JC, McClay DR. Evolution of the Wnt pathways. Methods in Molecular Biology (Clifton, N.J.). 2008; 469: 3\u201318.","DOI":"10.1007\/978-1-60327-469-2_1"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F. A new locus for Parkinson\u2019s disease (PARK8) maps to chromosome 12p11.2-q13.1. Annals of Neurology. 2002; 51: 296\u2013301.","DOI":"10.1002\/ana.10113"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Pais\u00e1n-Ru\u00edz C, Jain S, Evans EW, Gilks WP, Sim\u00f3n J, van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson\u2019s disease. Neuron. 2004; 44: 595\u2013600.","DOI":"10.1016\/j.neuron.2004.10.023"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004; 44: 601\u2013607.","DOI":"10.1016\/j.neuron.2004.11.005"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Orenstein SJ, Kuo SH, Tasset I, Arias E, Koga H, Fernandez-Carasa I, et al. Interplay of LRRK2 with chaperone-mediated autophagy. Nature Neuroscience. 2013; 16: 394\u2013406.","DOI":"10.1038\/nn.3350"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Migheli R, Del Giudice MG, Spissu Y, Sanna G, Xiong Y, Dawson TM, et al. LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization. PloS One. 2013; 8: e77198.","DOI":"10.1371\/journal.pone.0077198"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Ju\u00e1rez-Flores DL, Gonz\u00e1lez-Casacuberta I, Ezquerra M, Ba\u00f1\u00f3 M, Carmona-Pontaque F, Catal\u00e1n-Garc\u00eda M, et al. Exhaustion of mitochondrial and autophagic reserve may contribute to the development of LRRK2 G2019S -Parkinson\u2019s disease. Journal of Translational Medicine. 2018; 16: 160.","DOI":"10.1186\/s12967-018-1526-3"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Nguyen HN, Byers B, Cord B, Shcheglovitov A, Byrne J, Gujar P, et al. LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell. 2011; 8: 267\u2013280.","DOI":"10.1016\/j.stem.2011.01.013"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Kluss JH, Mamais A, Cookson MR. LRRK2 links genetic and sporadic Parkinson\u2019s disease. Biochemical Society Transactions. 2019; 47: 651\u2013661.","DOI":"10.1042\/BST20180462"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Wu YC, Sonninen TM, Peltonen S, Koistinaho J, Lehtonen \u0160. Blood-Brain Barrier and Neurodegenerative Diseases-Modeling with iPSC-Derived Brain Cells. International Journal of Molecular Sciences. 2021; 22: 7710.","DOI":"10.3390\/ijms22147710"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Wang C, Xue Y, Markovic T, Li H, Wang S, Zhong Y, et al. Blood-brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system. Nature Materials. 2025; 24: 1653-1663.","DOI":"10.1038\/s41563-024-02114-5"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Jagaran K, Singh M. Lipid Nanoparticles: Promising Treatment Approach for Parkinson\u2019s Disease. International Journal of Molecular Sciences. 2022; 23: 9361.","DOI":"10.3390\/ijms23169361"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Talwar P, Saha P, Mohan A, Divya S, Ravanan P. Drug delivery to the brain using endocytic receptors as carriers. In Neuroreceptor Endocytosis and Signaling in Health and Disease (pp. 435\u2013456). Springer: Cham, Switzerland. 2025.","DOI":"10.1007\/978-3-031-81991-9_19"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Yang F, Chen G. The nutritional functions of dietary sphingomyelin and its applications in food. Frontiers in Nutrition. 2022; 9: 1002574.","DOI":"10.3389\/fnut.2022.1002574"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Jeon JH, Zhu H, Qin J, Wang L, Mou S, Langston LK, et al. Lipid Nanoparticles Formulated with a Novel Cholesterol-Tailed Ionizable Lipid Markedly Increase mRNA Delivery Both in vitro and in vivo. International Journal of Nanomedicine. 2025; 20: 9389\u20139405.","DOI":"10.2147\/IJN.S527822"},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"Ahmad M, Saleem S, Ahmad AS, Yousuf S, Ansari MA, Khan MB, et al. Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidences. Journal of Neurochemistry. 2005; 93: 94\u2013104.","DOI":"10.1111\/j.1471-4159.2005.03000.x"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"Jagaran K, Habib S, Singh M. Bio-Inspired Polymeric Solid Lipid Nanoparticles for siRNA Delivery: Cytotoxicity and Cellular Uptake In Vitro. Polymers. 2024; 16: 3265.","DOI":"10.3390\/polym16233265"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Singh M. Assessing nucleic acid: Cationic nanoparticle interaction for gene delivery. In Narayanan K (ed.) Bio-Carrier Vectors (pp. 43\u201355). Springer: New York, NY, USA. 2021.","DOI":"10.1007\/978-1-0716-0943-9_4"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Lugli E, Roederer M, Cossarizza A. Data analysis in flow cytometry: the future just started. Cytometry. Part a: the Journal of the International Society for Analytical Cytology. 2010; 77: 705\u2013713.","DOI":"10.1002\/cyto.a.20901"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Greggio E, Cookson M\u202fR, Savitt J\u202fM, Campbell K, Blackinton J, Farrer M\u202fJ, et\u202fal. The Parkinson disease\u2013associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intra molecular autophosphorylation. Journal of Biological Chemistry. 2008; 283:16906\u201316914.","DOI":"10.1074\/jbc.M708718200"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Veiko AG, Sekowski S, Lapshina EA, Wilczewska AZ, Markiewicz KH, Zamaraeva M, et al. Flavonoids modulate liposomal membrane structure, regulate mitochondrial membrane permeability and prevent erythrocyte oxidative damage. Biochimica et Biophysica Acta. Biomembranes. 2020; 1862: 183442.","DOI":"10.1016\/j.bbamem.2020.183442"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"Gachowska M, Szlasa W, Saczko J, Kulbacka J. Neuroregulatory role of ginkgolides. Molecular Biology Reports. 2021; 48: 5689\u20135697.","DOI":"10.1007\/s11033-021-06535-2"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"Syahputra RA, Dalimunthe A, Utari ZD, Halim P, Sukarno MA, Zainalabidin S, et al. Nanotechnology and flavonoids: current research and future perspectives on cardiovascular health. Journal of Functional Foods. 2024; 120: 106355.","DOI":"10.1016\/j.jff.2024.106355"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"West AB, Moore DJ, Choi C, Andrabi SA, Li X, Dikeman D, et al. Parkinson\u2019s disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Human Molecular Genetics. 2007; 16: 223\u2013232.","DOI":"10.1093\/hmg\/ddl471"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"Cookson MR. The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson\u2019s disease. Nature Reviews. Neuroscience. 2010; 11: 791\u2013797.","DOI":"10.1038\/nrn2935"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"Andreu Z, Y\u00e1\u00f1ez-M\u00f3 M. Tetraspanins in extracellular vesicle formation and function. Frontiers in Immunology. 2014; 5: 442.","DOI":"10.3389\/fimmu.2014.00442"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"Chiasserini D, van Weering JRT, Piersma SR, Pham TV, Malekzadeh A, Teunissen CE, et al. Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset. Journal of Proteomics. 2014; 106: 191\u2013204.","DOI":"10.1016\/j.jprot.2014.04.028"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"de Rus Jacquet A, Tancredi JL, Lemire AL, DeSantis MC, Li WP, O\u2019Shea EK. The LRRK2 G2019S mutation alters astrocyte-to-neuron communication via extracellular vesicles and induces neuron atrophy in a human iPSC-derived model of Parkinson\u2019s disease. eLife. 2021; 10: e73062.","DOI":"10.7554\/eLife.73062"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"Lin CH, Tsai PI, Wu RM, Chien CT. LRRK2 G2019S mutation induces dendrite degeneration through mislocalization and phosphorylation of tau by recruiting autoactivated GSK3\u00df. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience. 2010; 30: 13138\u201313149.","DOI":"10.1523\/JNEUROSCI.1737-10.2010"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"Smith JV, Luo Y. Studies on molecular mechanisms of Ginkgo biloba extract. Applied Microbiology and Biotechnology. 2004; 64: 465\u2013472.","DOI":"10.1007\/s00253-003-1527-9"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"Xiong B, Lu JJ, Guo H, Huang M, Li T. Ginkgetin from Ginkgo biloba: mechanistic insights into anticancer efficacy. Natural Products and Bioprospecting. 2025; 15: 50.","DOI":"10.1007\/s13659-025-00535-6"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"Kim H, Kang S, Go GW. Exploring the multifaceted role of ginkgolides and bilobalide from Ginkgo biloba in mitigating metabolic disorders. Food Science and Biotechnology. 2024; 33: 2903\u20132917.","DOI":"10.1007\/s10068-024-01656-3"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"Guo N, Wang X, Xu M, Bai J, Yu H, Le Zhang. PI3K\/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression. Pharmacological Research. 2024; 206: 107300.","DOI":"10.1016\/j.phrs.2024.107300"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"Ahlemeyer B, Krieglstein J. Neuroprotective effects of Ginkgo biloba extract. Cellular and Molecular Life Sciences: CMLS. 2003; 60: 1779\u20131792.","DOI":"10.1007\/s00018-003-3080-1"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"Nichols RJ, Dzamko N, Hutti JE, Cantley LC, Deak M, Moran J, et al. Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson\u2019s disease. The Biochemical Journal. 2009; 424: 47\u201360.","DOI":"10.1042\/BJ20091035"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"Kalita T, Dezfouli SA, Pandey LM, Uludag H. siRNA Functionalized Lipid Nanoparticles (LNPs) in Management of Diseases. Pharmaceutics. 2022; 14: 2520.","DOI":"10.3390\/pharmaceutics14112520"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"Bravo-San Pedro JM, Niso-Santano M, G\u00f3mez-S\u00e1nchez R, Pizarro-Estrella E, Aiastui-Pujana A, Gorostidi A, et al. The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK\/ERK pathway. Cellular and Molecular Life Sciences: CMLS. 2013; 70: 121\u2013136.","DOI":"10.1007\/s00018-012-1061-y"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, et al. (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Cell Death and Differentiation. 2012; 19: 1623\u20131633.","DOI":"10.1038\/cdd.2012.42"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"Henrich MT, Oertel WH, Surmeier DJ, Geibl FF. Mitochondrial dysfunction in Parkinson\u2019s disease - a key disease hallmark with therapeutic potential. Molecular Neurodegeneration. 2023; 18: 83.","DOI":"10.1186\/s13024-023-00676-7"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"Tanaka K, Galdur\u00f3z RFS, Gobbi LTB, Galdur\u00f3z JCF. Ginkgo biloba extract in an animal model of Parkinson\u2019s disease: a systematic review. Current Neuropharmacology. 2013; 11: 430\u2013435.","DOI":"10.2174\/1570159X11311040006"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"Lejri I, Agapouda A, Grimm A, Eckert A. Mitochondria- and Oxidative Stress-Targeting Substances in Cognitive Decline-Related Disorders: From Molecular Mechanisms to Clinical Evidence. Oxidative Medicine and Cellular Longevity. 2019; 2019: 9695412.","DOI":"10.1155\/2019\/9695412"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"Liu X, Hao W, Qin Y, Decker Y, Wang X, Burkart M, et al. Long-term treatment with Ginkgo biloba extract EGb 761 improves symptoms and pathology in a transgenic mouse model of Alzheimer\u2019s disease. Brain, Behavior, and Immunity. 2015; 46: 121\u2013131.","DOI":"10.1016\/j.bbi.2015.01.011"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"Beal MF. Mitochondria take center stage in aging and neurodegeneration. Annals of Neurology. 2005; 58: 495\u2013505.","DOI":"10.1002\/ana.20624"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"Wan W, Jin L, Wang Z, Wang L, Fei G, Ye F, et al. Iron Deposition Leads to Neuronal \u03b1-Synuclein Pathology by Inducing Autophagy Dysfunction. Frontiers in Neurology, 2017; 8: 1.","DOI":"10.3389\/fneur.2017.00001"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"Ravinther AI, Dewadas HD, Tong SR, Foo CN, Lin YE, Chien CT, et al. Molecular Pathways Involved in LRRK2-Linked Parkinson\u2019s Disease: A Systematic Review. International Journal of Molecular Sciences. 2022; 23: 11744.","DOI":"10.3390\/ijms231911744"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"van Attikum H, Gasser SM. Crosstalk between histone modifications during the DNA damage response. Trends in Cell Biology. 2009; 19: 207\u2013217.","DOI":"10.1016\/j.tcb.2009.03.001"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"Osipov A, Chigasova A, Yashkina E, Ignatov M, Fedotov Y, Molodtsova D, et al. Residual Foci of DNA Damage Response Proteins in Relation to Cellular Senescence and Autophagy in X-Ray Irradiated Fibroblasts. Cells. 2023; 12: 1209.","DOI":"10.3390\/cells12081209"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature. 2001; 411: 366\u2013374.","DOI":"10.1038\/35077232"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"Nicholls DG, Ferguson SJ. Bioenergetics. Academic Press: London, United Kingdom. 2013.","DOI":"10.1016\/C2010-0-64902-9"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"Di Maio R, Hoffman EK, Rocha EM, Keeney MT, Sanders LH, De Miranda BR, et al. LRRK2 activation in idiopathic Parkinson\u2019s disease. Science Translational Medicine. 2018; 10: eaar5429.","DOI":"10.1126\/scitranslmed.aar5429"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"Pal C. Targeting mitochondria with small molecules: A promising strategy for combating Parkinson\u2019s disease. Mitochondrion. 2024; 79: 101971.","DOI":"10.1016\/j.mito.2024.101971"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"Dhanya R, Kartha CC. Quercetin improves oxidative stress-induced pancreatic beta cell alterations via mTOR-signaling. Molecular and Cellular Biochemistry. 2021; 476: 3879\u20133887.","DOI":"10.1007\/s11010-021-04193-3"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"Dave A, Shukla F, Wala H, Pillai P. Mitochondrial Electron Transport Chain Complex Dysfunction in MeCP2 Knock-Down Astrocytes: Protective Effects of Quercetin Hydrate. Journal of Molecular Neuroscience: MN. 2019; 67: 16\u201327.","DOI":"10.1007\/s12031-018-1197-9"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"Lee MJ, Cho Y, Hwang Y, Jo Y, Kim YG, Lee SH, et al. Kaempferol Alleviates Mitochondrial Damage by Reducing Mitochondrial Reactive Oxygen Species Production in Lipopolysaccharide-Induced Prostate Organoids. Foods (Basel, Switzerland). 2023; 12: 3836.","DOI":"10.3390\/foods12203836"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"Chen M, Yan R, Luo J, Ning J, Zhou R, Ding L. The Role of PGC-1\u03b1-Mediated Mitochondrial Biogenesis in Neurons. Neurochemical Research. 2023; 48: 2595\u20132606.","DOI":"10.1007\/s11064-023-03934-8"}],"container-title":["Frontiers in Bioscience-Elite"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBE\/17\/4\/10.31083\/FBE44344","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T11:49:28Z","timestamp":1767872968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBE\/17\/4\/10.31083\/FBE44344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":60,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025]]}},"alternative-id":["S1945-0494(25)00202-4"],"URL":"https:\/\/doi.org\/10.31083\/fbe44344","relation":{},"ISSN":["1945-0494","1945-0508"],"issn-type":[{"value":"1945-0494","type":"print"},{"value":"1945-0508","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"article-number":"44344"}}