{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T10:04:37Z","timestamp":1793786677011,"version":"4.6.1"},"reference-count":184,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0 http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    The increasing prevalence of metabolic disorders and neurodegenerative diseases has uncovered shared pathophysiological pathways, with insulin resistance and mitochondrial dysfunction emerging as critical contributors to cognitive decline. Insulin resistance impairs neuronal metabolism and synaptic function, fostering neurodegeneration as observed in Alzheimer\u2019s disease and Down syndrome. Indeed, Down syndrome, characterized by the triplication of the\n                    <jats:italic toggle=\"yes\">APP<\/jats:italic>\n                    gene, represents a valuable genetic model for studying early-onset Alzheimer\u2019s disease and accelerated aging. Building on the link between metabolic dysfunctions and neurodegeneration, innovative strategies addressed brain insulin resistance as a key driver of cognitive decline. Intranasal insulin has shown promise in improving cognition in early Alzheimer\u2019s disease and type 2 diabetes, supporting the concept that restoring insulin sensitivity can mitigate neurodegeneration. However, insulin-based therapies risk desensitizing insulin signaling, potentially worsening the disease. Incretins, particularly glucagon-like peptide 1 receptor agonists, offer neuroprotective benefits by enhancing insulin sensitivity, metabolism, and synaptic plasticity while reducing oxidative distress and neuroinflammation. This review focuses on current knowledge on the metabolic and molecular interactions between insulin resistance, mitochondrial dynamics (including their roles in energy metabolism), and oxidative distress regulation, as these are pivotal in both Alzheimer\u2019s disease and Down syndrome. By addressing these interconnected mechanisms, innovative treatments may emerge for both metabolic and neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.4103\/nrr.nrr-d-25-00144","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T14:02:51Z","timestamp":1750341771000},"page":"2227-2237","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":22,"title":["Metabolic breakdown: Linking insulin resistance and mitochondrial dysfunction to neurodegeneration in Alzheimer\u2019s disease"],"prefix":"10.4103","volume":"21","author":[{"given":"Simona","family":"Lanzillotta","sequence":"first","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi-Fanelli\u201d, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia Romana","family":"Rolfi","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi-Fanelli\u201d, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Zulli","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi-Fanelli\u201d, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-4251","authenticated-orcid":false,"given":"Eugenio","family":"Barone","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi-Fanelli\u201d, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"R1-20260416","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1111\/j.1471-4159.2004.02914.x","article-title":"The expression of GLP\u20101 receptor mRNA and protein allows the effect of GLP\u20101 on glucose metabolism in the human hypothalamus and brainstem","volume":"92","author":"Alvarez","year":"2005","journal-title":"J Neurochem"},{"key":"R2-20260416","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/s41574-021-00626-7","article-title":"Mitochondrial and metabolic dysfunction in ageing and age-related diseases","volume":"18","author":"Amorim","year":"2022","journal-title":"Nat Rev Endocrinol"},{"key":"R3-20260416","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.neuroscience.2015.05.023","article-title":"Glucagon-like peptide-1 regulates mitochondrial biogenesis and tau phosphorylation against advanced glycation end product-induced neuronal insult: studies in vivo and in vitro","volume":"300","author":"An","year":"2015","journal-title":"Neuroscience"},{"key":"R4-20260416","doi-asserted-by":"crossref","first-page":"111932","DOI":"10.1016\/j.bbr.2019.111932","article-title":"Exenatide alleviates mitochondrial dysfunction and cognitive impairment in the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"370","author":"An","year":"2019","journal-title":"Behav Brain Res"},{"key":"R5-20260416","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1749-6632.1995.tb26696.x","article-title":"Localization of specific amino acids contributing to insulin specificity of the insulin receptor","volume":"766","author":"Andersen","year":"1995","journal-title":"Ann N Y Acad Sci"},{"key":"R6-20260416","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/1873-3468.12964","article-title":"Role of mitochondrial ROS in the brain: from physiology to neurodegeneration","volume":"592","author":"Angelova","year":"2018","journal-title":"FEBS Lett"},{"key":"R7-20260416","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41574-024-00979-9","article-title":"Targeting the incretin system in obesity and type 2 diabetes mellitus","volume":"20","author":"Ansari","year":"2024","journal-title":"Nat Rev Endocrinol"},{"key":"R8-20260416","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-019-0143-7","article-title":"Down syndrome","volume":"6","author":"Antonarakis","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"R9-20260416","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3390\/neurosci5020016","article-title":"In the brain, it is not all about sugar","volume":"5","author":"Antunes","year":"2024","journal-title":"NeuroSci"},{"key":"R10-20260416","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrneurol.2017.185","article-title":"Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums","volume":"14","author":"Arnold","year":"2018","journal-title":"Nat Rev Neurol"},{"key":"R11-20260416","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1002\/ana.25826","article-title":"Brain insulin signaling, Alzheimer disease pathology, and cognitive function","volume":"88","author":"Arvanitakis","year":"2020","journal-title":"Ann Neurol"},{"key":"R12-20260416","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/j.1750-3639.2011.00560.x","article-title":"Amyloid generation and dysfunctional immunoproteasome activation with disease progression in animal model of familial Alzheimer\u2019s disease","volume":"22","author":"Aso","year":"2012","journal-title":"Brain Pathol"},{"key":"R13-20260416","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.jalz.2019.01.010","article-title":"2019 Alzheimer\u2019s disease facts and figures","volume":"15","year":"2019","journal-title":"Alzheimers Dement"},{"key":"R14-20260416","doi-asserted-by":"crossref","first-page":"333","DOI":"10.4103\/1673-5374.317979","article-title":"Brain insulin resistance: an early risk factor for Alzheimer\u2019s disease development in Down syndrome","volume":"17","author":"Barone","year":"2022","journal-title":"Neural Regen Res"},{"key":"R15-20260416","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.freeradbiomed.2016.10.508","article-title":"HNE-modified proteins in Down syndrome: involvement in development of Alzheimer disease neuropathology","volume":"111","author":"Barone","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"R16-20260416","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.freeradbiomed.2017.07.009","article-title":"Disturbance of redox homeostasis in Down Syndrome: Role of iron dysmetabolism","volume":"114","author":"Barone","year":"2018","journal-title":"Free Radic Biol Med"},{"key":"R17-20260416","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1007\/s12035-018-1231-5","article-title":"Biliverdin reductase-A mediates the beneficial effects of intranasal insulin in Alzheimer disease","volume":"56","author":"Barone","year":"2019","journal-title":"Mol Neurobiol"},{"key":"R18-20260416","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.freeradbiomed.2021.09.006","article-title":"The interplay among oxidative stress, brain insulin resistance and AMPK dysfunction contribute to neurodegeneration in type 2 diabetes and Alzheimer disease","volume":"176","author":"Barone","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"R19-20260416","doi-asserted-by":"crossref","first-page":"1350239","DOI":"10.3389\/fnagi.2024.1350239","article-title":"Reduced GLP-1R availability in the caudate nucleus with Alzheimer\u2019s disease","volume":"16","author":"Barrett","year":"2024","journal-title":"Front Aging Neurosci"},{"key":"R20-20260416","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3109\/15622975.2011.650204","article-title":"Alzheimer\u2019s disease and type 2 diabetes: two diseases, one common link?","volume":"14","author":"Bartl","year":"2013","journal-title":"World J Biol Psychiatry"},{"key":"R21-20260416","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/sj.npp.1301193","article-title":"Intranasal insulin improves memory in humans: superiority of insulin aspart","volume":"32","author":"Benedict","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"R22-20260416","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/brain\/awac258","article-title":"Extracellular vesicle biomarkers for cognitive impairment in Parkinson\u2019s disease","volume":"146","author":"Blommer","year":"2023","journal-title":"Brain"},{"key":"R23-20260416","doi-asserted-by":"crossref","first-page":"793","DOI":"10.3233\/JAD-190237","article-title":"Exenatide reverts the high-fat-diet-induced impairment of BDNF signaling and inflammatory response in an animal model of Alzheimer\u2019s disease","volume":"70","author":"Bomba","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"R24-20260416","doi-asserted-by":"crossref","first-page":"5789","DOI":"10.3390\/molecules25245789","article-title":"Comprehensive review on Alzheimer\u2019s disease: Causes and treatment","volume":"25","author":"Breijyeh","year":"2020","journal-title":"Molecules"},{"key":"R25-20260416","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1111\/j.1471-4159.2009.06397.x","article-title":"Multifunctional roles of enolase in Alzheimer\u2019s disease brain: beyond altered glucose metabolism","volume":"111","author":"Butterfield","year":"2009","journal-title":"J Neurochem"},{"key":"R26-20260416","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41583-019-0132-6","article-title":"Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease","volume":"20","author":"Butterfield","year":"2019","journal-title":"Nat Rev Neurosci"},{"key":"R27-20260416","doi-asserted-by":"crossref","first-page":"818","DOI":"10.3390\/antiox9090818","article-title":"Mitochondrial oxidative and nitrosative stress and Alzheimer disease","volume":"9","author":"Butterfield","year":"2020","journal-title":"Antioxidants (Basel)"},{"key":"R28-20260416","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1038\/s41598-017-02838-2","article-title":"GLP-1 receptor signalling promotes beta-cell glucose metabolism via mTOR-dependent HIF-1alpha activation","volume":"7","author":"Carlessi","year":"2017","journal-title":"Sci Rep"},{"key":"R29-20260416","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.2337\/db11-1186","article-title":"Metabolic alterations induced by sucrose intake and Alzheimer\u2019s disease promote similar brain mitochondrial abnormalities","volume":"61","author":"Carvalho","year":"2012","journal-title":"Diabetes"},{"key":"R30-20260416","doi-asserted-by":"crossref","first-page":"1114231","DOI":"10.3389\/fphys.2023.1114231","article-title":"Mitochondria: it is all about energy","volume":"14","author":"Casanova","year":"2023","journal-title":"Front Physiol"},{"key":"R31-20260416","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev-pathmechdis-012419-032711","article-title":"Mitochondrial dynamics and its involvement in disease","volume":"15","author":"Chan","year":"2020","journal-title":"Annu Rev Pathol"},{"key":"R32-20260416","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.jocn.2020.09.054","article-title":"Semaglutide-mediated protection against Abeta correlated with enhancement of autophagy and inhibition of apotosis","volume":"81","author":"Chang","year":"2020","journal-title":"J Clin Neurosci"},{"key":"R33-20260416","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41392-023-01547-9","article-title":"Mitochondrial dynamics in health and disease: mechanisms and potential targets","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"R34-20260416","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s12035-012-8375-5","article-title":"A non-transgenic mouse model (icv-STZ mouse) of Alzheimer\u2019s disease: similarities to and differences from the transgenic model (3xTg-AD mouse)","volume":"47","author":"Chen","year":"2013","journal-title":"Mol Neurobiol"},{"key":"R35-20260416","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1126\/science.1171091","article-title":"S-nitrosylation of Drp1 mediates \u03b2-amyloid-related mitochondrial fission and neuronal injury","volume":"324","author":"Cho","year":"2009","journal-title":"Science"},{"key":"R36-20260416","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.3390\/ijms23105574","article-title":"Role of biliverdin reductase A in the regulation of insulin signaling in metabolic and neurodegenerative diseases: An update","volume":"23","author":"Cimini","year":"2022","journal-title":"Int J Mol Sci"},{"key":"R37-20260416","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1523\/JNEUROSCI.20-02-00558.2000","article-title":"Inflammatory mechanisms in Alzheimer\u2019s disease: inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists","volume":"20","author":"Combs","year":"2000","journal-title":"J Neurosci"},{"key":"R38-20260416","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.brainres.2011.12.063","article-title":"Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer\u2019s disease and diabetes interrelation","volume":"1441","author":"Correia","year":"2012","journal-title":"Brain Res"},{"key":"R39-20260416","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/j.cmet.2022.07.013","article-title":"LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept","volume":"34","author":"Coskun","year":"2022","journal-title":"Cell Metab"},{"key":"R40-20260416","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S1474-4422(04)00681-7","article-title":"Insulin and neurodegenerative disease: shared and specific mechanisms","volume":"3","author":"Craft","year":"2004","journal-title":"Lancet Neurol"},{"key":"R41-20260416","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.3233\/JAD-161256","article-title":"Effects of regular and long-acting insulin on cognition and Alzheimer\u2019s disease biomarkers: a pilot clinical trial","volume":"57","author":"Craft","year":"2017","journal-title":"J Alzheimers Dis"},{"key":"R42-20260416","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1001\/jamaneurol.2020.1840","article-title":"Safety, efficacy, and feasibility of intranasal insulin for the treatment of mild cognitive impairment and Alzheimer disease dementia: a randomized clinical trial","volume":"77","author":"Craft","year":"2020","journal-title":"JAMA Neurol"},{"key":"R43-20260416","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41573-020-0072-x","article-title":"Brain energy rescue: An emerging therapeutic concept for neurodegenerative disorders of ageing","volume":"19","author":"Cunnane","year":"2020","journal-title":"Nat Rev Drug Discov"},{"key":"R44-20260416","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev.ph.47.030185.002041","article-title":"The nature and regulation of the insulin receptor: structure and function","volume":"47","author":"Czech","year":"1985","journal-title":"Annu Rev Physiol"},{"key":"R45-20260416","doi-asserted-by":"crossref","first-page":"111898","DOI":"10.1016\/j.mad.2023.111898","article-title":"A feasibility study of the combination of intranasal insulin with oral semaglutide for cognition in older adults with metabolic syndrome at high dementia risk-study rationale and design","volume":"218","author":"Davidy","year":"2024","journal-title":"Mech Ageing Dev"},{"key":"R46-20260416","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/S0016-5085(98)70599-2","article-title":"Steatohepatitis: a tale of two \u201chits\u201d?","volume":"114","author":"Day","year":"1998","journal-title":"Gastroenterology"},{"key":"R47-20260416","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0031-19.2019","article-title":"Glucagon-like peptide-1 cleavage product improves cognitive function in a mouse model of Down syndrome","volume":"6","author":"Day","year":"2019","journal-title":"eNeuro"},{"key":"R48-20260416","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1177\/193229680800200619","article-title":"Alzheimer\u2019s disease is type 3 diabetes-evidence reviewed","volume":"2","author":"de la Monte","year":"2008","journal-title":"J Diabetes Sci Technol"},{"key":"R49-20260416","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.2337\/dc09-S302","article-title":"Skeletal muscle insulin resistance is the primary defect in type 2 diabetes","volume":"2","author":"DeFronzo","year":"2009","journal-title":"Diabetes Care 32 Suppl"},{"key":"R50-20260416","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1007\/s40618-024-02320-7","article-title":"Long-acting exenatide does not prevent cognitive decline in mild cognitive impairment: A proof-of-concept clinical trial","volume":"47","author":"Dei Cas","year":"2024","journal-title":"J Endocrinol Invest"},{"key":"R51-20260416","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol Neurodegener"},{"key":"R52-20260416","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1089\/ars.2016.6759","article-title":"The triangle of death in Alzheimer\u2019s disease brain: The aberrant cross-talk among energy metabolism, mammalian target of rapamycin signaling, and protein homeostasis revealed by redox proteomics","volume":"26","author":"Di Domenico","year":"2017","journal-title":"Antioxid Redox Signal"},{"key":"R53-20260416","doi-asserted-by":"crossref","first-page":"670","DOI":"10.3389\/fnins.2020.00670","article-title":"Down syndrome is a metabolic disease: altered insulin signaling mediates peripheral and brain dysfunctions","volume":"14","author":"Dierssen","year":"2020","journal-title":"Front Neurosci"},{"key":"R54-20260416","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.4103\/1673-5374.389626","article-title":"Glucagon-like peptide 1 receptor activation: anti-inflammatory effects in the brain","volume":"19","author":"Diz-Chaves","year":"2024","journal-title":"Neural Regen Res"},{"key":"R55-20260416","doi-asserted-by":"crossref","first-page":"1033479","DOI":"10.3389\/fendo.2022.1033479","article-title":"The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer\u2019s disease","volume":"13","author":"Du","year":"2022","journal-title":"Front Endocrinol"},{"key":"R56-20260416","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1002\/alz.12130","article-title":"Extracellular vesicle biomarkers of Alzheimer\u2019s disease associated with sub-clinical cognitive decline in late middle age","volume":"16","author":"Eren","year":"2020","journal-title":"Alzheimers Dement"},{"key":"R57-20260416","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1113\/JP273185","article-title":"Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation","volume":"595","author":"Evans","year":"2017","journal-title":"J Physiol"},{"key":"R58-20260416","doi-asserted-by":"crossref","first-page":"815","DOI":"10.7150\/ijbs.20052","article-title":"FOXO signaling pathways as therapeutic targets in cancer","volume":"13","author":"Farhan","year":"2017","journal-title":"Int J Biol Sci"},{"key":"R59-20260416","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s13063-019-3259-x","article-title":"Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer\u2019s disease: study protocol for a randomised controlled trial (ELAD study)","volume":"20","author":"Femminella","year":"2019","journal-title":"Trials"},{"key":"R60-20260416","doi-asserted-by":"crossref","first-page":"108277","DOI":"10.1016\/j.pharmthera.2022.108277","article-title":"Incretin-based drugs as potential therapy for neurodegenerative diseases: current status and perspectives","volume":"239","author":"Ferrari","year":"2022","journal-title":"Pharmacol Ther"},{"key":"R61-20260416","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/S1474-4422(21)00245-3","article-title":"Alzheimer\u2019s disease associated with Down syndrome: a genetic form of dementia","volume":"20","author":"Fortea","year":"2021","journal-title":"Lancet Neurol"},{"key":"R62-20260416","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s40265-023-01992-4","article-title":"Tirzepatide: a review in type 2 diabetes","volume":"84","author":"France","year":"2024","journal-title":"Drugs"},{"key":"R63-20260416","doi-asserted-by":"crossref","first-page":"8429","DOI":"10.1002\/alz.14275","article-title":"Inhibiting mtDNA transcript translation alters Alzheimer\u2019s disease-associated biology","volume":"20","author":"Gabrielli","year":"2024","journal-title":"Alzheimers Dement"},{"key":"R64-20260416","first-page":"943","article-title":"Insulin and its key role for mitochondrial function\/dysfunction and quality control: a shared link between dysmetabolism and neurodegeneration","volume":"11","author":"Galizzi","year":"2022","journal-title":"Biology (Basel)"},{"key":"R65-20260416","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.neuint.2019.04.006","article-title":"Exendin-4 attenuates brain mitochondrial toxicity through PI3K\/Akt-dependent pathway in amyloid beta (1-42)-induced cognitive deficit rats","volume":"128","author":"Garabadu","year":"2019","journal-title":"Neurochem Int"},{"key":"R66-20260416","doi-asserted-by":"crossref","first-page":"854","DOI":"10.3109\/10715762.2013.830717","article-title":"Mitochondrial dysfunction in non-alcoholic fatty liver disease and insulin resistance: cause or consequence?","volume":"47","author":"Garcia-Ruiz","year":"2013","journal-title":"Free Radic Res"},{"key":"R67-20260416","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol Cancer"},{"key":"R68-20260416","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.3389\/fnins.2019.01112","article-title":"Glucagon-like peptide-1: a focus on neurodegenerative diseases","volume":"13","author":"Grieco","year":"2019","journal-title":"Front Neurosci"},{"key":"R69-20260416","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.brainres.2009.08.005","article-title":"Insulin-stimulated translocation of GLUT4 to the plasma membrane in rat hippocampus is PI3-kinase dependent","volume":"1296","author":"Grillo","year":"2009","journal-title":"Brain Res"},{"key":"R70-20260416","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13024-020-00391-7","article-title":"Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer\u2019s disease","volume":"15","author":"Guo","year":"2020","journal-title":"Mol Neurodegener"},{"key":"R71-20260416","doi-asserted-by":"crossref","first-page":"341","DOI":"10.32598\/bcn.2021.2554.2","article-title":"Investigating the glucagon-like peptide-1 and its receptor in human brain: distribution of expression, functional implications, age-related changes and species specific characteristics","volume":"14","author":"Gupta","year":"2023","journal-title":"Basic Clin Neurosci"},{"key":"R72-20260416","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nrm.2017.89","article-title":"Biochemical and cellular properties of insulin receptor signalling","volume":"19","author":"Haeusler","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"R73-20260416","first-page":"65","article-title":"Mitochondria and cell death: a pore way to die?","volume":"52","author":"Halestrap","year":"2000","journal-title":"Symp Soc Exp Biol"},{"key":"R74-20260416","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s40263-020-00781-x","article-title":"Intranasal insulin for Alzheimer\u2019s disease","volume":"35","author":"Hallschmid","year":"2021","journal-title":"CNS Drugs"},{"key":"R75-20260416","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.brainres.2015.12.052","article-title":"The GLP-1 receptor agonist liraglutide reduces pathology-specific tau phosphorylation and improves motor function in a transgenic hTauP301L mouse model of tauopathy","volume":"1634","author":"Hansen","year":"2016","journal-title":"Brain Res"},{"key":"R76-20260416","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.2337\/diabetes.48.10.1915","article-title":"No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans","volume":"48","author":"Hasselbalch","year":"1999","journal-title":"Diabetes"},{"key":"R77-20260416","doi-asserted-by":"crossref","first-page":"5737","DOI":"10.1073\/pnas.75.11.5737","article-title":"Identification of insulin in rat brain","volume":"75","author":"Havrankova","year":"1978","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R78-20260416","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/s41392-021-00828-5","article-title":"Targeting PI3K\/Akt signal transduction for cancer therapy","volume":"6","author":"He","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"R79-20260416","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":"R80-20260416","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fnagi.2019.00088","article-title":"Insulin signaling impairment in the brain as a risk factor in Alzheimer\u2019s disease","volume":"11","author":"Holscher","year":"2019","journal-title":"Front Aging Neurosci"},{"key":"R81-20260416","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2337\/diab.33.2.153","article-title":"Insulin dose-response characteristics among individual muscle and adipose tissues measured in the rat in vivo with 3[H]2-deoxyglucose","volume":"33","author":"Hom","year":"1984","journal-title":"Diabetes"},{"key":"R82-20260416","doi-asserted-by":"crossref","first-page":"a008946","DOI":"10.1101\/cshperspect.a008946","article-title":"The insulin receptor: both a prototypical and atypical receptor tyrosine kinase","volume":"5","author":"Hubbard","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"R83-20260416","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide once weekly for the treatment of obesity","volume":"387","author":"Jastreboff","year":"2022","journal-title":"N Engl J Med"},{"key":"R84-20260416","doi-asserted-by":"crossref","first-page":"28","DOI":"10.7570\/jomes22012","article-title":"The upcoming weekly tides (semaglutide vs. tirzepatide) against obesity: Step or surpass?","volume":"31","author":"Jung","year":"2022","journal-title":"J Obes Metab Syndr"},{"key":"R85-20260416","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.neuron.2014.01.045","article-title":"ApoE and Abeta in Alzheimer\u2019s disease: Accidental encounters or partners?","volume":"81","author":"Kanekiyo","year":"2014","journal-title":"Neuron"},{"key":"R86-20260416","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S1474-4422(20)30231-3","article-title":"Brain insulin resistance in Alzheimer\u2019s disease and related disorders: Mechanisms and therapeutic approaches","volume":"19","author":"Kellar","year":"2020","journal-title":"Lancet Neurol"},{"key":"R87-20260416","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1038\/s41598-022-05165-3","article-title":"Intranasal insulin modulates cerebrospinal fluid markers of neuroinflammation in mild cognitive impairment and Alzheimer\u2019s disease: a randomized trial","volume":"12","author":"Kellar","year":"2022","journal-title":"Sci Rep"},{"key":"R88-20260416","doi-asserted-by":"crossref","first-page":"e14519","DOI":"10.1002\/alz.14519","article-title":"Decoding brain structure to stage Alzheimer\u2019s disease pathology in Down syndrome","volume":"21","author":"Kennedy","year":"2025","journal-title":"Alzheimers Dement"},{"key":"R89-20260416","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1161\/CIRCRESAHA.107.165472","article-title":"Role of mitochondrial dysfunction in insulin resistance","volume":"102","author":"Kim","year":"2008","journal-title":"Circ Res"},{"key":"R90-20260416","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/s41586-021-03510-6","article-title":"Distinct fission signatures predict mitochondrial degradation or biogenesis","volume":"593","author":"Kleele","year":"2021","journal-title":"Nature"},{"key":"R91-20260416","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/jne.12433","article-title":"Deciphering brain insulin receptor and insulin-like growth factor 1 receptor signalling","volume":"28","author":"Kleinridders","year":"2016","journal-title":"J Neuroendocrinol"},{"key":"R92-20260416","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s40263-019-00658-8","article-title":"Targeting mitochondria in Alzheimer disease: rationale and perspectives","volume":"33","author":"Lanzillotta","year":"2019","journal-title":"CNS Drugs"},{"key":"R93-20260416","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.freeradbiomed.2021.01.042","article-title":"Insulin resistance, oxidative stress and mitochondrial defects in Ts65dn mice brain: a harmful synergistic path in down syndrome","volume":"165","author":"Lanzillotta","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"R94-20260416","doi-asserted-by":"crossref","first-page":"106523","DOI":"10.1016\/j.nbd.2024.106523","article-title":"Shaping down syndrome brain cognitive and molecular changes due to aging using adult animals from the Ts66Yah murine model","volume":"196","author":"Lanzillotta","year":"2024","journal-title":"Neurobiol Dis"},{"key":"R95-20260416","doi-asserted-by":"crossref","first-page":"103221","DOI":"10.1016\/j.redox.2024.103221","article-title":"Biliverdin reductase-A integrates insulin signaling with mitochondrial metabolism through phosphorylation of GSK3beta","volume":"73","author":"Lanzillotta","year":"2024","journal-title":"Redox Biol"},{"key":"R96-20260416","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.freeradbiomed.2024.11.043","article-title":"Altered mitochondrial unfolded protein response and protein quality control promote oxidative distress in Down syndrome brain","volume":"227","author":"Lanzillotta","year":"2025","journal-title":"Free Radic Biol Med"},{"key":"R97-20260416","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41392-022-01073-0","article-title":"Trends in insulin resistance: insights into mechanisms and therapeutic strategy","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"R98-20260416","first-page":"32","article-title":"Mitochondrial quality control in human health and disease","volume":"11","author":"Liu","year":"2024","journal-title":"Mil Med Res"},{"key":"R99-20260416","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"R100-20260416","doi-asserted-by":"crossref","first-page":"14417","DOI":"10.3390\/ijms232214417","article-title":"The role of insulin signaling in hippocampal-related diseases: a focus on Alzheimer\u2019s disease","volume":"23","author":"Liu","year":"2022","journal-title":"Int J Mol Sci"},{"key":"R101-20260416","doi-asserted-by":"crossref","first-page":"1013295","DOI":"10.3389\/fnagi.2022.1013295","article-title":"Clinical characteristics and genotype-phenotype correlation analysis of familial Alzheimer\u2019s disease patients with pathogenic\/likely pathogenic amyloid protein precursor mutations","volume":"14","author":"Liu","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"R102-20260416","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.neuroscience.2011.02.023","article-title":"Preproglucagon neurons project widely to autonomic control areas in the mouse brain","volume":"180","author":"Llewellyn-Smith","year":"2011","journal-title":"Neuroscience"},{"key":"R103-20260416","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S1474-4422(10)70112-5","article-title":"Cognitive deficits and associated neurological complications in individuals with Down\u2019s syndrome","volume":"9","author":"Lott","year":"2010","journal-title":"Lancet Neurol"},{"key":"R104-20260416","first-page":"956","article-title":"Oxidative stress concept updated: definitions, classifications, and regulatory pathways implicated","volume":"20","author":"Lushchak","year":"2021","journal-title":"EXCLI J"},{"key":"R105-20260416","doi-asserted-by":"crossref","first-page":"10068","DOI":"10.3390\/ijms251810068","article-title":"Emerging role of extracellular vesicles as biomarkers in neurodegenerative diseases and their clinical and therapeutic potential in central nervous system pathologies","volume":"25","author":"Malaguarnera","year":"2024","journal-title":"Int J Mol Sci"},{"key":"R106-20260416","doi-asserted-by":"crossref","first-page":"le3","DOI":"10.1074\/jbc.L110.133520","article-title":"Curcumin and Alzheimer disease: this marriage is not to be performed","volume":"286","author":"Mancuso","year":"2011","journal-title":"J Biol Chem"},{"key":"R107-20260416","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","article-title":"AKT\/PKB signaling: navigating the network","volume":"169","author":"Manning","year":"2017","journal-title":"Cell"},{"key":"R108-20260416","doi-asserted-by":"crossref","first-page":"483","DOI":"10.3389\/fimmu.2016.00483","article-title":"Regulation of chemokine activity\u2013a focus on the role of dipeptidyl peptidase IV\/CD26","volume":"7","author":"Metzemaekers","year":"2016","journal-title":"Front Immunol"},{"key":"R109-20260416","doi-asserted-by":"crossref","first-page":"617588","DOI":"10.3389\/fnagi.2021.617588","article-title":"Mitochondrial dysfunction and oxidative stress in Alzheimer\u2019s disease","volume":"13","author":"Misrani","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"R110-20260416","doi-asserted-by":"crossref","first-page":"3134","DOI":"10.3390\/ijms21093134","article-title":"Targeting mitochondrial network architecture in Down syndrome and aging","volume":"21","author":"Mollo","year":"2020","journal-title":"Int J Mol Sci"},{"key":"R111-20260416","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.3390\/cells11132023","article-title":"GLP-1 receptor agonists in neurodegeneration: neurovascular unit in the spotlight","volume":"11","author":"Monti","year":"2022","journal-title":"Cells"},{"key":"R112-20260416","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.3390\/cells11132023","article-title":"GLP-1 receptor agonists in neurodegeneration: neurovascular unit in the spotlight","volume":"11","author":"Monti","year":"2022","journal-title":"Cells"},{"key":"R113-20260416","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2174\/1567205016666190913155950","article-title":"A pilot study of exenatide actions in Alzheimer\u2019s disease","volume":"16","author":"Mullins","year":"2019","journal-title":"Curr Alzheimer Res"},{"key":"R114-20260416","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/B978-0-12-800101-1.00002-8","article-title":"Regulation of glucose homeostasis by GLP-1","volume":"121","author":"Nadkarni","year":"2014","journal-title":"Prog Mol Biol Transl Sci"},{"key":"R115-20260416","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3389\/fnagi.2017.00345","article-title":"Insulin resistance and Alzheimer\u2019s disease: bioenergetic linkages","volume":"9","author":"Neth","year":"2017","journal-title":"Front Aging Neurosci"},{"key":"R116-20260416","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.devcel.2021.02.009","article-title":"Quality control of the mitochondrion","volume":"56","author":"Ng","year":"2021","journal-title":"Dev Cell"},{"key":"R117-20260416","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1007\/s11064-020-03031-0","article-title":"Role of insulin resistance in the Alzheimer\u2019s disease progression","volume":"45","author":"Nguyen","year":"2020","journal-title":"Neurochem Res"},{"key":"R118-20260416","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.3390\/ijms21093165","article-title":"Type 3 diabetes and its role implications in Alzheimer\u2019s disease","volume":"21","author":"Nguyen","year":"2020","journal-title":"Int J Mol Sci"},{"key":"R119-20260416","first-page":"1598","article-title":"Alzheimer\u2019s disease facts and figures","volume":"19","year":"2023","journal-title":"Alzheimers Dement"},{"key":"R120-20260416","doi-asserted-by":"crossref","first-page":"176776","DOI":"10.1016\/j.ejphar.2024.176776","article-title":"Liraglutide alleviated alpha-pyrrolidinovalerophenone (alpha-PVP) induced cognitive deficits in rats by modifying brain mitochondrial impairment","volume":"978","author":"Noruzi","year":"2024","journal-title":"Eur J Pharmacol"},{"key":"R121-20260416","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41380-022-01792-4","article-title":"Incretin and insulin signaling as novel therapeutic targets for Alzheimer\u2019s and Parkinson\u2019s disease","volume":"28","author":"Nowell","year":"2023","journal-title":"Mol Psychiatry"},{"key":"R122-20260416","doi-asserted-by":"crossref","first-page":"101979","DOI":"10.1016\/j.arr.2023.101979","article-title":"Antidiabetic agents as a novel treatment for Alzheimer\u2019s and Parkinson\u2019s disease","volume":"89","author":"Nowell","year":"2023","journal-title":"Ageing Res Rev"},{"key":"R123-20260416","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3390\/ijms19010026","article-title":"Effects of glucagon-like peptide-1 on oxidative stress and Nrf2 signaling","volume":"19","author":"Oh","year":"2017","journal-title":"Int J Mol Sci"},{"key":"R124-20260416","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11010-007-9643-y","article-title":"The protective role of carotenoids against 7-keto-cholesterol formation in solution","volume":"309","author":"Palozza","year":"2008","journal-title":"Mol Cell Biochem"},{"key":"R125-20260416","doi-asserted-by":"crossref","first-page":"11301","DOI":"10.3390\/ijms241411301","article-title":"Potential role of glucagon-like peptide-1 receptor agonists in the treatment of cognitive decline and dementia in diabetes mellitus","volume":"24","author":"Pelle","year":"2023","journal-title":"Int J Mol Sci"},{"key":"R126-20260416","doi-asserted-by":"crossref","first-page":"724904","DOI":"10.1155\/2012\/724904","article-title":"Oxidative stress and Down syndrome: a route toward Alzheimer-like dementia","volume":"2012","author":"Perluigi","year":"2012","journal-title":"Curr Gerontol Geriatr Res"},{"key":"R127-20260416","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1002\/alz.12499","article-title":"Aberrant crosstalk between insulin signaling and mTOR in young Down syndrome individuals revealed by neuronal-derived extracellular vesicles","volume":"18","author":"Perluigi","year":"2022","journal-title":"Alzheimers Dement"},{"key":"R128-20260416","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1152\/physrev.00030.2022","article-title":"Oxidative damage in neurodegeneration: Roles in the pathogenesis and progression of Alzheimer disease","volume":"104","author":"Perluigi","year":"2024","journal-title":"Physiol Rev"},{"key":"R129-20260416","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of insulin action and insulin resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol Rev"},{"key":"R130-20260416","doi-asserted-by":"crossref","first-page":"E268","DOI":"10.1152\/ajpendo.00314.2018","article-title":"Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis","volume":"316","author":"Pinti","year":"2019","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"R131-20260416","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.tem.2005.01.008","article-title":"The role of insulin receptor signaling in the brain","volume":"16","author":"Plum","year":"2005","journal-title":"Trends Endocrinol Metab"},{"key":"R132-20260416","doi-asserted-by":"crossref","first-page":"376509","DOI":"10.1155\/2011\/376509","article-title":"Activation of the GLP-1 receptor signalling pathway: a relevant strategy to repair a deficient beta-cell mass","volume":"2011","author":"Portha","year":"2011","journal-title":"Exp Diabetes Res"},{"key":"R133-20260416","doi-asserted-by":"crossref","first-page":"74","DOI":"10.2337\/db12-0148","article-title":"Interaction between the central and peripheral effects of insulin in controlling hepatic glucose metabolism in the conscious dog","volume":"62","author":"Ramnanan","year":"2013","journal-title":"Diabetes"},{"key":"R134-20260416","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13024-022-00574-4","article-title":"ApoE in Alzheimer\u2019s disease: pathophysiology and therapeutic strategies","volume":"17","author":"Raulin","year":"2022","journal-title":"Mol Neurodegener"},{"key":"R135-20260416","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jhep.2009.11.030","article-title":"Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model","volume":"52","author":"Rector","year":"2010","journal-title":"J Hepatol"},{"key":"R136-20260416","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3389\/fnins.2019.00521","article-title":"Role of the blood-brain barrier in central nervous system insulin resistance","volume":"13","author":"Rhea","year":"2019","journal-title":"Front Neurosci"},{"key":"R137-20260416","doi-asserted-by":"crossref","first-page":"689","DOI":"10.3390\/molecules21060689","article-title":"The rationale for insulin therapy in Alzheimer\u2019s disease","volume":"21","author":"Ribaric","year":"2016","journal-title":"Molecules"},{"key":"R138-20260416","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1161\/CIRCRESAHA.116.306206","article-title":"Insulin signaling and heart failure","volume":"118","author":"Riehle","year":"2016","journal-title":"Circ Res"},{"key":"R139-20260416","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3233\/JAD-2005-8304","article-title":"Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer\u2019s disease: Link to brain reductions in acetylcholine","volume":"8","author":"Rivera","year":"2005","journal-title":"J Alzheimers Dis"},{"key":"R140-20260416","doi-asserted-by":"crossref","first-page":"672","DOI":"10.3389\/fendo.2018.00672","article-title":"Pleiotropic effects of GLP-1 and analogs on cell signaling, metabolism, and function","volume":"9","author":"Rowlands","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"R141-20260416","doi-asserted-by":"crossref","first-page":"e146353","DOI":"10.1172\/JCI146353","article-title":"GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice","volume":"131","author":"Samms","year":"2021","journal-title":"J Clin Invest"},{"key":"R142-20260416","doi-asserted-by":"crossref","first-page":"e12932","DOI":"10.1111\/jne.12932","article-title":"Untangling the effect of insulin action on brain mitochondria and metabolism","volume":"33","author":"Schell","year":"2021","journal-title":"J Neuroendocrinol"},{"key":"R143-20260416","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1016\/j.clinthera.2007.08.021","article-title":"Diffusion into use of exenatide for glucose control in diabetes mellitus: a retrospective cohort study of a new therapy","volume":"29","author":"Segal","year":"2007","journal-title":"Clin Ther"},{"key":"R144-20260416","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.nbd.2019.02.003","article-title":"Loss of biliverdin reductase-A favors tau hyper-phosphorylation in Alzheimer\u2019s disease","volume":"125","author":"Sharma","year":"2019","journal-title":"Neurobiol Dis"},{"key":"R145-20260416","doi-asserted-by":"crossref","first-page":"113537","DOI":"10.1016\/j.intimp.2024.113537","article-title":"Neuroprotective effects of GLP-1 receptor agonists in neurodegenerative disorders: a large-scale propensity-matched cohort study","volume":"143","author":"Siddeeque","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"R146-20260416","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/s41556-018-0124-1","article-title":"The multifaceted contributions of mitochondria to cellular metabolism","volume":"20","author":"Spinelli","year":"2018","journal-title":"Nat Cell Biol"},{"key":"R147-20260416","doi-asserted-by":"crossref","first-page":"788","DOI":"10.3389\/fnins.2019.00788","article-title":"Brain insulin resistance and hippocampal plasticity: Mechanisms and biomarkers of cognitive decline","volume":"13","author":"Spinelli","year":"2019","journal-title":"Front Neurosci"},{"key":"R148-20260416","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s12933-018-0800-2","article-title":"GLP-1RAs in type 2 diabetes: Mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data","volume":"17","author":"Sposito","year":"2018","journal-title":"Cardiovasc Diabetol"},{"key":"R149-20260416","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000508054","article-title":"Brain fuel utilization in the developing brain","volume":"1","author":"Steiner","year":"2019","journal-title":"Ann Nutr Metab 75 Suppl"},{"key":"R150-20260416","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbadis.2009.09.013","article-title":"Abnormal mitochondrial dynamics and neurodegenerative diseases","volume":"1802","author":"Su","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"R151-20260416","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1084\/jem.20150892","article-title":"Qualitative changes in human gamma-secretase underlie familial Alzheimer\u2019s disease","volume":"212","author":"Szaruga","year":"2015","journal-title":"J Exp Med"},{"key":"R152-20260416","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1172\/JCI59903","article-title":"Demonstrated brain insulin resistance in Alzheimer\u2019s disease patients is associated with IGF-1 resistance, IRS\u20131 dysregulation, and cognitive decline","volume":"122","author":"Talbot","year":"2012","journal-title":"J Clin Invest"},{"key":"R153-20260416","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrm1837","article-title":"Critical nodes in signalling pathways: Insights into insulin action","volume":"7","author":"Taniguchi","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"key":"R154-20260416","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3389\/fendo.2019.00299","article-title":"Editorial: Insulin and the brain","volume":"10","author":"Taouis","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"R155-20260416","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.3233\/JAD-161088","article-title":"Oxidative stress, synaptic dysfunction, and Alzheimer\u2019s disease","volume":"57","author":"Tonnies","year":"2017","journal-title":"J Alzheimers Dis"},{"key":"R156-20260416","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/jnc.13037","article-title":"Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD","volume":"133","author":"Tramutola","year":"2015","journal-title":"J Neurochem"},{"key":"R157-20260416","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1089\/ars.2016.6686","article-title":"Polyubiquitinylation profile in Down syndrome brain before and after the development of Alzheimer neuropathology","volume":"26","author":"Tramutola","year":"2017","journal-title":"Antioxid Redox Signal"},{"key":"R158-20260416","doi-asserted-by":"crossref","first-page":"104772","DOI":"10.1016\/j.nbd.2020.104772","article-title":"Brain insulin resistance triggers early onset Alzheimer disease in Down syndrome","volume":"137","author":"Tramutola","year":"2020","journal-title":"Neurobiol Dis"},{"key":"R159-20260416","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3390\/antiox12010111","article-title":"Intranasal administration of KYCCSRK peptide rescues brain insulin signaling activation and reduces Alzheimer\u2019s disease-like neuropathology in a mouse model for Down syndrome","volume":"12","author":"Tramutola","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"R160-20260416","doi-asserted-by":"crossref","first-page":"123001","DOI":"10.1016\/j.lfs.2024.123001","article-title":"Repurposing antidiabetic drugs for Alzheimer\u2019s disease: a review of preclinical and clinical evidence and overcoming challenges","volume":"355","author":"Tran","year":"2024","journal-title":"Life Sci"},{"key":"R161-20260416","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1016\/j.bbadis.2018.07.005","article-title":"Biliverdin reductase-A impairment links brain insulin resistance with increased Abeta production in an animal model of aging: Implications for Alzheimer disease","volume":"1864","author":"Triani","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"R162-20260416","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/S0140-6736(22)02033-5","article-title":"LY3437943, a novel triple GIP, GLP\u20131, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial","volume":"400","author":"Urva","year":"2022","journal-title":"Lancet"},{"key":"R163-20260416","doi-asserted-by":"crossref","first-page":"132931","DOI":"10.1016\/j.neulet.2017.06.050","article-title":"Inflammation and mitochondrial dysfunction: a vicious circle in neurodegenerative disorders?","volume":"710","author":"van Horssen","year":"2019","journal-title":"Neurosci Lett"},{"key":"R164-20260416","doi-asserted-by":"crossref","first-page":"e047993","DOI":"10.1136\/bmjopen-2020-047993","article-title":"Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson\u2019s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: the \u2018Exenatide-PD3\u2019 study","volume":"11","author":"Vijiaratnam","year":"2021","journal-title":"BMJ Open"},{"key":"R165-20260416","doi-asserted-by":"crossref","first-page":"e39157","DOI":"10.1016\/j.heliyon.2024.e39157","article-title":"Genetic variability of incretin receptors affects the occurrence of neurodegenerative diseases and their characteristics","volume":"10","author":"Vogrinc","year":"2024","journal-title":"Heliyon"},{"key":"R166-20260416","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.cell.2016.07.002","article-title":"Mitochondria and cancer","volume":"166","author":"Vyas","year":"2016","journal-title":"Cell"},{"key":"R167-20260416","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1039\/C8FO02460J","article-title":"Lycopene ameliorates systemic inflammation-induced synaptic dysfunction via improving insulin resistance and mitochondrial dysfunction in the liver\u2013brain axis","volume":"10","author":"Wang","year":"2019","journal-title":"Food Funct"},{"key":"R168-20260416","doi-asserted-by":"crossref","first-page":"e22196","DOI":"10.1002\/syn.22196","article-title":"Mitochondria-associated endoplasmic reticulum membranes: at the crossroad between familiar and sporadic Alzheimer\u2019s disease","volume":"75","author":"Wang","year":"2021","journal-title":"Synapse"},{"key":"R169-20260416","doi-asserted-by":"crossref","first-page":"4118","DOI":"10.1093\/hmg\/ddx299","article-title":"Inhibition of mitochondrial fragmentation protects against Alzheimer\u2019s disease in rodent model","volume":"26","author":"Wang","year":"2017","journal-title":"Hum Mol Genet"},{"key":"R170-20260416","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3389\/fimmu.2020.00202","article-title":"Glycolysis and oxidative phosphorylation play critical roles in natural killer cell receptor-mediated natural killer cell functions","volume":"11","author":"Wang","year":"2020","journal-title":"Front Immunol"},{"key":"R171-20260416","doi-asserted-by":"crossref","first-page":"109716","DOI":"10.1016\/j.neuropharm.2023.109716","article-title":"Semaglutide ameliorates cognition and glucose metabolism dysfunction in the 3xTg mouse model of Alzheimer\u2019s disease via the GLP-1R\/SIRT1\/GLUT4 pathway","volume":"240","author":"Wang","year":"2023","journal-title":"Neuropharmacology"},{"key":"R172-20260416","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1126\/science.1092952","article-title":"Insulin signaling in health and disease","volume":"302","author":"White","year":"2003","journal-title":"Science"},{"key":"R173-20260416","doi-asserted-by":"crossref","first-page":"20932","DOI":"10.1074\/jbc.M411320200","article-title":"Characterization of the functional insulin binding epitopes of the full-length insulin receptor","volume":"280","author":"Whittaker","year":"2005","journal-title":"J Biol Chem"},{"key":"R174-20260416","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s12640-021-00460-9","article-title":"Liraglutide regulates mitochondrial quality control system through PGC-1alpha in a mouse model of Parkinson\u2019s disease","volume":"40","author":"Wu","year":"2022","journal-title":"Neurotox Res"},{"key":"R175-20260416","doi-asserted-by":"crossref","first-page":"114578","DOI":"10.1016\/j.bcp.2021.114578","article-title":"GLP-1 improves the neuronal supportive ability of astrocytes in Alzheimer\u2019s disease by regulating mitochondrial dysfunction via the cAMP\/PKA pathway","volume":"188","author":"Xie","year":"2021","journal-title":"Biochem Pharmacol"},{"key":"R176-20260416","doi-asserted-by":"crossref","first-page":"e41351","DOI":"10.7554\/eLife.41351","article-title":"Mitochondrial fusion supports increased oxidative phosphorylation during cell proliferation","volume":"8","author":"Yao","year":"2019","journal-title":"Elife"},{"key":"R177-20260416","doi-asserted-by":"crossref","first-page":"14670","DOI":"10.1073\/pnas.0903563106","article-title":"Mitochondrial bioenergetic deficit precedes Alzheimer\u2019s pathology in female mouse model of Alzheimer\u2019s disease","volume":"106","author":"Yao","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R178-20260416","doi-asserted-by":"crossref","first-page":"e54059","DOI":"10.1371\/journal.pone.0054059","article-title":"Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice","volume":"8","author":"Yuzefovych","year":"2013","journal-title":"PLoS One"},{"key":"R179-20260416","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.bbamcr.2011.03.010","article-title":"Akt, FoxO and regulation of apoptosis","volume":"1813","author":"Zhang","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"R180-20260416","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.3892\/mmr.2014.3124","article-title":"Silencing miR-106b improves palmitic acid-induced mitochondrial dysfunction and insulin resistance in skeletal myocytes","volume":"11","author":"Zhang","year":"2015","journal-title":"Mol Med Rep"},{"key":"R181-20260416","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3389\/fendo.2020.00561","article-title":"High-intensity interval training restores glycolipid metabolism and mitochondrial function in skeletal muscle of mice with type 2 diabetes","volume":"11","author":"Zheng","year":"2020","journal-title":"Front Endocrinol"},{"key":"R182-20260416","doi-asserted-by":"crossref","first-page":"104966","DOI":"10.1016\/j.phrs.2020.104966","article-title":"Lycopene in protection against obesity and diabetes: a mechanistic review","volume":"159","author":"Zhu","year":"2020","journal-title":"Pharmacol Res"},{"key":"R183-20260416","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/j.biocel.2009.02.004","article-title":"Role of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes","volume":"41","author":"Zorzano","year":"2009","journal-title":"Int J Biochem Cell Biol"},{"key":"R184-20260416","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13813450802676335","article-title":"Mitochondrial dynamics as a bridge between mitochondrial dysfunction and insulin resistance","volume":"115","author":"Zorzano","year":"2009","journal-title":"Arch Physiol Biochem"}],"container-title":["Neural Regeneration Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/NRR.NRR-D-25-00144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:00:52Z","timestamp":1787756452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/NRR.NRR-D-25-00144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,19]]},"references-count":184,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/nrr.nrr-d-25-00144","relation":{},"ISSN":["1673-5374","1876-7958"],"issn-type":[{"value":"1673-5374","type":"print"},{"value":"1876-7958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,19]]},"assertion":[{"value":"2025-01-30","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-09","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}