{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:53:02Z","timestamp":1793969582138,"version":"4.8.0"},"reference-count":106,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","ibroneuroscience.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuroscience"],"published-print":{"date-parts":[[2023,2]]},"DOI":"10.1016\/j.neuroscience.2022.12.003","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T11:16:42Z","timestamp":1670411802000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":47,"special_numbering":"C","title":["Mitochondrial Dysfunction in Down Syndrome: From Pathology to Therapy"],"prefix":"10.1016","volume":"511","author":[{"given":"Kai-Leng","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Chung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pike-See","family":"Cheah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"King-Hwa","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuroscience.2022.12.003_b0005","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2021.707950","article-title":"Oxidative phosphorylation is dysregulated within the basocortical circuit in a 6-month old mouse model of down syndrome and Alzheimer's disease","volume":"13","author":"Alldred","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0010","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-015-0138-y","article-title":"Down syndrome: An insight of the disease","volume":"22","author":"Asim","year":"2015","journal-title":"J Biomed Sci"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0015","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1093\/emboj\/17.16.4848","article-title":"The mtDNA-encoded ND6 subunit of mitochondrial NADH dehydrogenase is essential for the assembly of the membrane arm and the respiratory function of the enzyme","volume":"17","author":"Bai","year":"1998","journal-title":"EMBO J"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0020","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.brainres.2007.10.045","article-title":"Mitochondrial dysfunction in mouse trisomy 16 brain","volume":"1188","author":"Bambrick","year":"2008","journal-title":"Brain Res"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2021.101871","article-title":"Down syndrome is an oxidative phosphorylation disorder","volume":"41","author":"Bayona-Bafaluy","year":"2021","journal-title":"Redox Biol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0030","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0165-3806(98)00070-4","article-title":"Cytoplasmic abnormalities in cultured cerebellar neurons from the trisomy 16 mouse","volume":"109","author":"Bersu","year":"1998","journal-title":"Dev Brain Res"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-019-1752-5","article-title":"mTOR hyperactivation in Down Syndrome underlies deficits in autophagy induction, autophagosome formation, and mitophagy","volume":"10","author":"Bordi","year":"2019","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0040","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1183\/09031936.00122812","article-title":"Effect of oxidative stress on respiratory epithelium from children with Down syndrome","volume":"42","author":"Bruijn","year":"2013","journal-title":"Eur Respir J"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0050","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S0896-6273(02)00604-9","article-title":"Altered metabolism of the amyloid \u03b2 precursor protein is associated with mitochondrial dysfunction in Down's syndrome","volume":"33","author":"Busciglio","year":"2002","journal-title":"Neuron"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0055","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/378776a0","article-title":"Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro","volume":"378","author":"Busciglio","year":"1995","journal-title":"Nat"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0060","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-20834-y","article-title":"Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism","volume":"8","author":"Caracausi","year":"2018","journal-title":"Sci Rep."},{"key":"10.1016\/j.neuroscience.2022.12.003_b0065","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.mce.2012.03.023","article-title":"Roles of transcriptional corepressor RIP140 and coactivator PGC-1\u03b1 in energy state of chronically infarcted rat hearts and mitochondrial function of cardiomyocytes","volume":"362","author":"Chen","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0070","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00726-007-0618-9","article-title":"Protein expression of BACE1, BACE2 and APP in Down syndrome brains","volume":"35","author":"Cheon","year":"2008","journal-title":"Amino Acids"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0075","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-07630-y","article-title":"Trisomy silencing by XIST normalizes Down syndrome cell pathogenesis demonstrated for hematopoietic defects in vitro","volume":"9","author":"Chiang","year":"2018","journal-title":"Nat Commun"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0080","doi-asserted-by":"crossref","first-page":"13893","DOI":"10.1096\/fj.201901230RR","article-title":"Prep1 regulates angiogenesis through a PGC-1A\u2013mediated mechanism","volume":"33","author":"Cimmino","year":"2019","journal-title":"FASEB J"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0085","first-page":"287","article-title":"Ultrastructural features of skeletal muscle in adult and aging Ts65Dn mice, a murine model of Down syndrome","volume":"3","author":"Cisterna","year":"2013","journal-title":"Muscles Ligaments Tendons J"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0090","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2164-8-268","article-title":"Altered expression of mitochondrial and extracellular matrix genes in the heart of human fetuses with chromosome 21 trisomy","volume":"8","author":"Conti","year":"2007","journal-title":"BMC Genomics"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0095","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.bbr.2017.07.022","article-title":"Pre- and post-natal melatonin administration partially regulates brain oxidative stress but does not improve cognitive or histological alterations in the Ts65Dn mouse model of Down syndrome","volume":"334","author":"Corrales","year":"2017","journal-title":"Behav Brain Res"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0100","doi-asserted-by":"crossref","first-page":"737","DOI":"10.3233\/JAD-160278","article-title":"Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate Between Down Syndrome and Alzheimer's Disease","volume":"55","author":"Coskun","year":"2017","journal-title":"J Alzheimer's Dis"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0105","doi-asserted-by":"crossref","first-page":"S293","DOI":"10.3233\/JAD-2010-100351","article-title":"Systemic Mitochondrial Dysfunction and the Etiology of Alzheimer\u2019s Disease and Down Syndrome Dementia","volume":"20","author":"Coskun","year":"2010","journal-title":"J Alzheimer\u2019s Dis"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0110","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.bbagen.2011.08.008","article-title":"A mitochondrial etiology of Alzheimer and Parkinson disease","volume":"1820","author":"Coskun","year":"2012","journal-title":"Biochim Biophys Acta \u2013 Gen Subj"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0115","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.redox.2017.07.003","article-title":"Oxidant production and SOD1 protein expression in single skeletal myofibers from Down syndrome mice","volume":"13","author":"Cowley","year":"2017","journal-title":"Redox Biol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0120","article-title":"Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome","volume":"7","author":"D'Acunzo","year":"2021","journal-title":"Sci Adv"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0125","first-page":"1281","article-title":"Cu\/Zn-superoxide dismutase and glutathione peroxidase during aging","volume":"35","author":"De Haan","year":"1995","journal-title":"Biochem Mol Biol Int"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0130","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a015008","article-title":"Mitochondrial biogenesis through activation of nuclear signaling proteins","volume":"5","author":"Dominy","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0135","doi-asserted-by":"crossref","first-page":"14088","DOI":"10.1074\/jbc.M111.305342","article-title":"Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells","volume":"287","author":"Ermak","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0140","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1101\/gad.4.6.1023","article-title":"NRF-1: a trans-activator of nuclear-encoded respiratory genes in animal cells","volume":"4","author":"Evans","year":"1990","journal-title":"Genes Dev"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0145","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1101\/gad.1152204","article-title":"Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1\u03b1: modulation by p38 MAPK","volume":"18","author":"Fan","year":"2004","journal-title":"Genes Dev"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0150","first-page":"884S","article-title":"Regulation of PGC-1\u03b1, a nodal regulator of mitochondrial biogenesis","volume":"vol. 93","author":"Fernandez-Marcos","year":"2011"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0155","doi-asserted-by":"crossref","DOI":"10.1093\/hmg\/9.11.1681","article-title":"DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways","volume":"9","author":"Fuentes","year":"2000","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0160","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s10519-006-9051-1","article-title":"Transcriptional Dysregulation in down syndrome: predictions for altered protein complex stoichiometries and post-translational modifications, and consequences for learning\/behavior genes ELK, CREB, and the estrogen and glucocorticoid receptors","volume":"36","author":"Gardiner","year":"2006","journal-title":"Behav Genet"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0165","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/dneu.22716","article-title":"Plasma metabolites related to cellular energy metabolism are altered in adults with Down syndrome and Alzheimer's disease","volume":"79","author":"Gross","year":"2019","journal-title":"Dev Neurobiol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0170","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Heiden","year":"2009","journal-title":"Science (80-.)"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0175","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cmet.2012.12.005","article-title":"Adaptive downregulation of mitochondrial function in down syndrome","volume":"17","author":"Helguera","year":"2013","journal-title":"Cell Metab"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0180","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1093\/hmg\/ddu157","article-title":"NRIP1\/RIP140 siRNA-mediated attenuation counteracts mitochondrial dysfunction in Down syndrome","volume":"23","author":"Izzo","year":"2014","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0185","first-page":"1056","article-title":"Metformin restores the mitochondrial network and reverses mitochondrial dysfunction in Down syndrome cells","volume":"26","author":"Izzo","year":"2017","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0190","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/8737649","article-title":"Overexpression of Chromosome 21 miRNAs May Affect Mitochondrial Function in the Hearts of Down Syndrome Fetuses","volume":"2017","author":"Izzo","year":"2017","journal-title":"Int J Genomics"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0195","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s10020-018-0004-y","article-title":"Mitochondrial dysfunction in down syndrome: Molecular mechanisms and therapeutic targets","volume":"24","author":"Izzo","year":"2018","journal-title":"Mol Med"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0200","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1006\/nbdi.2000.0299","volume":"7","author":"Jaarsma","year":"2000","journal-title":"Neurobiol Dis"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0205","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.cll.2011.08.002","article-title":"Constitutional and acquired autosomal aneuploidy","volume":"31","author":"Jackson-Cook","year":"2011","journal-title":"Clin Lab Med"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0210","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/nature12394","article-title":"Translating dosage compensation to trisomy 21","volume":"500","author":"Jiang","year":"2013","journal-title":"Nat"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0215","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1042\/bse0470069","article-title":"Regulation of mitochondrial biogenesis","volume":"47","author":"Jornayvaz","year":"2010","journal-title":"Essays Biochem"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0220","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.imr.2014.09.004","article-title":"Exercise-induced PGC-1\u03b1 transcriptional factors in skeletal muscle","volume":"3","author":"Jung","year":"2014","journal-title":"Integr Med Res"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0225","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1128\/MCB.01232-13","article-title":"Pknox1\/Prep1 regulates mitochondrial oxidative phosphorylation components in skeletal muscle","volume":"34","author":"Kanzleiter","year":"2014","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0230","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1203\/00006450-197201000-00002","article-title":"Efficiency of the glycolytic pathway in erythrocytes of children with down\u2019s syndrome","volume":"6","author":"Kedziora","year":"1972","journal-title":"Pediatr Res"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0235","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.tins.2017.01.002","article-title":"Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms","volume":"40","author":"Kerr","year":"2017","journal-title":"Trends Neurosci"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0240","first-page":"268","article-title":"Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management","volume":"10","author":"Kidd","year":"2005","journal-title":"Altern Med Rev"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0245","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1007\/PL00000661","article-title":"Decreased levels of complex III core protein 1 and complex V \u03b2 chain in brains from patients with Alzheimer's disease and Down syndrome","volume":"57","author":"Kim","year":"2000","journal-title":"Cell Mol Life Sci C"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0250","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1016\/S0024-3205(01)01074-8","article-title":"The reduction of NADH: Ubiquinone oxidoreductase 24- and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer's disease","volume":"68","author":"Kim","year":"2001","journal-title":"Life Sci"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0255","first-page":"39","article-title":"Two novel mutations in the gene in a patient with mitochondrial myopathy","volume":"22","author":"K\u00f6rver-Keularts","year":"2015","journal-title":"JIMD Rep"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0260","article-title":"Differential display reveals deteriorated mRNA levels of NADH3 (complex I) in cerebellum of patients with Down Syndrome","volume":"211\u2013220","author":"Krapfenbauer","year":"1999","journal-title":"J Neural Transm Suppl"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0265","doi-asserted-by":"crossref","first-page":"543","DOI":"10.14348\/molcells.2016.0050","article-title":"MiR-144-3p and its target gene \u03b2-amyloid precursor protein regulate 1-methyl-4-phenyl-1,2\u20133,6-tetrahydropyridine-induced mitochondrial dysfunction","volume":"39","author":"Li","year":"2016","journal-title":"Mol. Cells"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0270","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0378-1119(97)00279-5","article-title":"The human mitochondrial elongation factor tu (EF-Tu) gene: cDNA sequence, genomic localization, genomic structure, and identification of a pseudogene","volume":"197","author":"Ling","year":"1997","journal-title":"Gene"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0275","doi-asserted-by":"crossref","first-page":"e22126","DOI":"10.1371\/journal.pone.0022126","article-title":"S100B and APP promote a gliocentric shift and impaired neurogenesis in down syndrome neural progenitors","volume":"6","author":"Lu","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0280","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.neuron.2015.03.035","article-title":"A cellular perspective on brain energy metabolism and functional imaging","volume":"86","author":"Magistretti","year":"2015","journal-title":"Neuron"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0285","first-page":"9","article-title":"Red blood cell glucose metabolism in Down's syndrome","volume":"5","author":"Magnani","year":"1987","journal-title":"Clin Physiol Biochem"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0290","doi-asserted-by":"crossref","first-page":"S609","DOI":"10.3233\/JAD-2010-100564","article-title":"Mitochondria-targeted antioxidants protect against amyloid-\u03b2 toxicity in Alzheimer's disease neurons","volume":"20","author":"Manczak","year":"2010","journal-title":"J Alzheimer's Dis"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0295","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.pediatrneurol.2007.08.003","article-title":"Coenzyme Q10 (Ubiquinol-10) supplementation improves oxidative imbalance in children with trisomy 21","volume":"37","author":"Miles","year":"2007","journal-title":"Pediatr Neurol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0300","doi-asserted-by":"crossref","first-page":"606","DOI":"10.3389\/fgene.2019.00606","article-title":"Pioglitazone improves mitochondrial organization and bioenergetics in down syndrome cells","volume":"10","author":"Mollo","year":"2019","journal-title":"Front Genet"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0305","doi-asserted-by":"crossref","first-page":"18769","DOI":"10.1073\/pnas.1911895116","article-title":"Overproduction of H2S, generated by CBS, inhibits mitochondrial Complex IV and suppresses oxidative phosphorylation in down syndrome","volume":"116","author":"Panagaki","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0310","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1161\/CIRCRESAHA.117.311522","article-title":"Down syndrome critical region 1 gene, rcan1, helps maintain a more fused mitochondrial network","volume":"122","author":"Parra","year":"2018","journal-title":"Circ Res"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0315","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/520316","article-title":"RCAN1 regulates mitochondrial function and increases susceptibility to oxidative stress in mammalian cells","volume":"2014","author":"Peiris","year":"2014","journal-title":"Oxid Med Cell Longev"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0320","first-page":"505","article-title":"Mito-morphosis: Mitochondrial fusion, fission, and cristae remodeling as key mediators of cellular function","volume":"78","author":"Pernas","year":"2016","journal-title":"10.1146\/annurev-physiol-021115-105011"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0325","doi-asserted-by":"crossref","first-page":"e84031","DOI":"10.1371\/journal.pone.0084031","article-title":"Defective mitochondrial function in vivo in skeletal muscle in adults with down's syndrome: A 31P-MRS study","volume":"8","author":"Phillips","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0330","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1093\/hmg\/dds529","article-title":"Chronic pro-oxidative state and mitochondrial dysfunctions are more pronounced in fibroblasts from Down syndrome foeti with congenital heart defects","volume":"22","author":"Piccoli","year":"2013","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0335","series-title":"Down syndrome : advances in biomedicine and the behavioral sciences","author":"Pueschel","year":"1982"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0340","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.bbadis.2015.04.004","article-title":"Chromosome 21-derived hsa-miR-155-5p regulates mitochondrial biogenesis by targeting Mitochondrial Transcription Factor A (TFAM)","volume":"1852","author":"Qui\u00f1ones-Lombra\u00f1a","year":"2015","journal-title":"Biochim Biophys Acta \u2013 Mol Basis Dis"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0345","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.febslet.2006.12.058","article-title":"Mitochondrial alterations and tendency to apoptosis in peripheral blood cells from children with Down syndrome","volume":"581","author":"Roat","year":"2007","journal-title":"FEBS Lett"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0350","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13244-019-0729-3","article-title":"Neuroimaging assessment in Down syndrome: a pictorial review","volume":"10","author":"Rodrigues","year":"2019","journal-title":"Insights Imaging"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0355","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/509241","article-title":"Intracellular oxidant activity, antioxidant enzyme defense system, and cell senescence in fibroblasts with trisomy 21","volume":"2015","author":"Rodr\u00edguez-Sureda","year":"2015","journal-title":"Oxid Med Cell Longev"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0360","doi-asserted-by":"crossref","first-page":"26184","DOI":"10.1074\/jbc.M109.038943","article-title":"SUMOylation Attenuates the Function of PGC-1\u03b1","volume":"284","author":"Rytinki","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0365","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1093\/nar\/gkg396","article-title":"Overexpression of FABP7 in Down syndrome fetal brains is associated with PKNOX1 gene-dosage imbalance","volume":"31","author":"S\u00e1nchez-Font","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0370","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0891-5849(99)00226-9","article-title":"Increased mitochondrial superoxide generation in neurons from trisomy 16 mice: a model of Down's syndrome","volume":"28","author":"Schuchmann","year":"2000","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0375","doi-asserted-by":"crossref","first-page":"7216","DOI":"10.1523\/JNEUROSCI.18-18-07216.1998","article-title":"Altered Ca2+ signaling and mitochondrial deficiencies in hippocampal neurons of trisomy 16 mice: A model of down's syndrome","volume":"18","author":"Schuchmann","year":"1998","journal-title":"J Neurosci"},{"issue":"2907","key":"10.1016\/j.neuroscience.2022.12.003_b0380","article-title":"Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome","volume":"36","author":"Schupf","year":"2015","journal-title":"Neurobiol Aging"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0385","doi-asserted-by":"crossref","first-page":"e0223014","DOI":"10.1371\/journal.pone.0223014","article-title":"Mitochondrial fragmentation and network architecture in degenerative diseases","volume":"14","author":"Shah","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0390","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/j.1471-4159.2011.07581.x","article-title":"Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer's disease","volume":"120","author":"Sheng","year":"2012","journal-title":"J Neurochem"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0395","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.freeradbiomed.2004.05.019","article-title":"Aberrant neuronal and mitochondrial proteins in hippocampus of transgenic mice overexpressing human Cu\/Zn superoxide dismutase 1","volume":"37","author":"Shin","year":"2004","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0400","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1093\/hmg\/ddl211","article-title":"Mitochondrial dysfunction and tau hyperphosphorylation in Ts1Cje, a mouse model for Down syndrome","volume":"15","author":"Shukkur","year":"2006","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0405","doi-asserted-by":"crossref","first-page":"7113","DOI":"10.1007\/s12035-019-1585-3","article-title":"Transcriptome and proteome profiling of neural induced pluripotent stem cells from individuals with Down syndrome disclose dynamic dysregulations of key pathways and cellular functions","volume":"56","author":"Sobol","year":"2019","journal-title":"Mol Neurobiol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0410","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.molcel.2019.09.009","article-title":"AUTACs: Cargo-Specific Degraders Using Selective Autophagy","volume":"76","author":"Takahashi","year":"2019","journal-title":"Mol Cell"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0415","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1042\/EBC20170104","article-title":"Mitochondrial dynamics: overview of molecular mechanisms","volume":"62","author":"Tilokani","year":"2018","journal-title":"Essays Biochem"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0420","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1515\/JPEM.2010.23.3.277","article-title":"Melatonin and elimination of Kynurenines in children with down's syndrome","volume":"23","author":"Uberos","year":"2010","journal-title":"J Pediatr Endocrinol Metab"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0425","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.clnu.2015.04.012","article-title":"Green tea EGCG plus fish oil omega-3 dietary supplements rescue mitochondrial dysfunctions and are safe in a Down's syndrome child","volume":"34","author":"Vacca","year":"2015","journal-title":"Clin Nutr"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0430","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1016\/j.bbadis.2017.09.014","article-title":"Inhibition of Drp1-mediated mitochondrial fission improves mitochondrial dynamics and bioenergetics stimulating neurogenesis in hippocampal progenitor cells from a Down syndrome mouse model","volume":"1863","author":"Valenti","year":"2017","journal-title":"Biochim Biophys Acta \u2013 Mol Basis Dis"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0435","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.bbadis.2016.03.003","article-title":"The polyphenols resveratrol and epigallocatechin-3-gallate restore the severe impairment of mitochondria in hippocampal progenitor cells from a Down syndrome mouse model","volume":"1862","author":"Valenti","year":"2016","journal-title":"Biochim Biophys Acta \u2013 Mol Basis Dis"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0440","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.freeradbiomed.2017.08.014","article-title":"Mitochondria as pharmacological targets in Down syndrome","volume":"114","author":"Valenti","year":"2018","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0445","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.bbadis.2012.12.011","article-title":"Epigallocatechin-3-gallate prevents oxidative phosphorylation deficit and promotes mitochondrial biogenesis in human cells from subjects with Down's syndrome","volume":"1832","author":"Valenti","year":"2013","journal-title":"Biochim Biophys Acta \u2013 Mol Basis Dis"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0450","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1042\/BJ20100581","article-title":"Impairment of F1F0-ATPase, adenine nucleotide translocator and adenylate kinase causes mitochondrial energy deficit in human skin fibroblasts with chromosome 21 trisomy","volume":"431","author":"Valenti","year":"2010","journal-title":"Biochem J"},{"issue":"Pt 2","key":"10.1016\/j.neuroscience.2022.12.003_b0455","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.neubiorev.2014.01.012","article-title":"Mitochondrial dysfunction as a central actor in intellectual disability-related diseases: an overview of Down syndrome, autism, Fragile X and Rett syndrome","volume":"46","author":"Valenti","year":"2014","journal-title":"Neurosci Biobehav Rev"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0460","article-title":"Impaired brain mitochondrial bioenergetics in the Ts65Dn mouse model of down syndrome is restored by neonatal treatment with the polyphenol 7,8-dihydroxyflavone","volume":"11","author":"Valenti","year":"2021","journal-title":"Antioxidants (Basel, Switzerland)"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0465","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.pedhc.2006.02.006","article-title":"Part II: Clinical practice guidelines for adolescents and young adults with down syndrome: 12 to 21 years","volume":"20","author":"Van Cleve","year":"2006","journal-title":"J Pediatr Heal Care"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0470","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.pedhc.2005.10.004","article-title":"Part I: Clinical practice guidelines for children with down syndrome from birth to 12 years","volume":"20","author":"Van Cleve","year":"2006","journal-title":"J Pediatr Heal Care"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0475","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1093\/cvr\/cvn098","article-title":"Transcriptional control of mitochondrial biogenesis: the central role of PGC-1\u03b1","volume":"79","author":"Ventura-Clapier","year":"2008","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0480","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.bbabio.2016.03.030","article-title":"Bioenergetic relevance of hydrogen sulfide and the interplay between gasotransmitters at human cystathionine \u03b2-synthase","volume":"1857","author":"Vicente","year":"2016","journal-title":"Biochim Biophys Acta - Bioenerg"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0485","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1073\/pnas.91.4.1309","article-title":"Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: A potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis","volume":"91","author":"Virbasius","year":"1994","journal-title":"Proc Nati Acad Sci USA"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0490","doi-asserted-by":"crossref","first-page":"19318","DOI":"10.1073\/pnas.0804871105","article-title":"Amyloid-\u03b2 overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission\/fusion proteins","volume":"105","author":"Wang","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0495","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s00401-015-1499-8","article-title":"RCAN1 overexpression promotes age-dependent mitochondrial dysregulation related to neurodegeneration in Alzheimer's disease","volume":"130","author":"Wong","year":"2015","journal-title":"Acta Neuropathol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0500","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"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0505","doi-asserted-by":"crossref","DOI":"10.1098\/rsob.170167","article-title":"Protein SUMOylation modification and its associations with disease","volume":"7","author":"Yang","year":"2017","journal-title":"Open Biol"},{"issue":"6","key":"10.1016\/j.neuroscience.2022.12.003_b0510","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/nrm1697","article-title":"Mitochondrial fission in apoptosis","volume":"68","author":"Youle","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0515","doi-asserted-by":"crossref","DOI":"10.3390\/brainsci12010083","article-title":"Evidence of energy metabolism alterations in cultured neonatal astrocytes derived from the Ts65Dn mouse model of down syndrome","volume":"12","author":"Zampieri","year":"2022","journal-title":"Brain Sci"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0520","doi-asserted-by":"crossref","first-page":"e12812","DOI":"10.1111\/acel.12812","article-title":"Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells","volume":"17","author":"Zamponi","year":"2018","journal-title":"Aging Cell"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0525","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.neurobiolaging.2006.03.008","article-title":"Oxidative stress: A bridge between Down's syndrome and Alzheimer's disease","volume":"28","author":"Zana","year":"2007","journal-title":"Neurobiol Aging"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0530","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1326-6-27","article-title":"Biology and pathophysiology of the amyloid precursor protein","volume":"6","author":"Zheng","year":"2011","journal-title":"Mol Neurodegener"},{"key":"10.1016\/j.neuroscience.2022.12.003_b0535","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-017-1354-4","article-title":"CRISPR\/Cas9-mediated targeted chromosome elimination","volume":"18","author":"Zuo","year":"2017","journal-title":"Genome Biol"}],"container-title":["Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452222006030?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452222006030?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T16:15:48Z","timestamp":1759680948000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0306452222006030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":106,"alternative-id":["S0306452222006030"],"URL":"https:\/\/doi.org\/10.1016\/j.neuroscience.2022.12.003","relation":{},"ISSN":["0306-4522"],"issn-type":[{"value":"0306-4522","type":"print"}],"subject":[],"published":{"date-parts":[[2023,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mitochondrial Dysfunction in Down Syndrome: From Pathology to Therapy","name":"articletitle","label":"Article Title"},{"value":"Neuroscience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuroscience.2022.12.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 IBRO. Published by Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}