{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:46:29Z","timestamp":1792791989845,"version":"4.5.0"},"reference-count":268,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>A growing number of clinical and epidemiological studies support the hypothesis of a tight correlation between type 2 diabetes mellitus (T2DM) and the development risk of Alzheimer\u2019s disease (AD). Indeed, the proposed definition of Alzheimer\u2019s disease as type 3 diabetes (T3D) underlines the key role played by deranged insulin signaling to accumulation of aggregated amyloid beta (A\u03b2) peptides in the senile plaques of the brain. Metabolic disturbances such as hyperglycemia, peripheral hyperinsulinemia, dysregulated lipid metabolism, and chronic inflammation associated with T2DM are responsible for an inefficient transport of insulin to the brain, producing a neuronal insulin resistance that triggers an enhanced production and deposition of A\u03b2 and concomitantly contributes to impairment in the micro-tubule-associated protein Tau, leading to neural degeneration and cognitive decline. Furthermore, the reduced antioxidant capacity observed in T2DM patients, together with the impairment of cerebral glucose metabolism and the decreased performance of mitochondrial activity, suggests the existence of a relationship between oxidative damage, mitochondrial impairment, and cognitive dysfunction that could further reinforce the common pathophysiology of T2DM and AD. In this review, we discuss the molecular mechanisms by which insulin-signaling dysregulation in T2DM can contribute to the pathogenesis and progression of AD, deepening the analysis of complex mechanisms involved in reactive oxygen species (ROS) production under oxidative stress and their possible influence in AD and T2DM. In addition, the role of current therapies as tools for prevention or treatment of damage induced by oxidative stress in T2DM and AD will be debated.<\/jats:p>","DOI":"10.3390\/antiox10081257","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T05:22:01Z","timestamp":1628227321000},"page":"1257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Diabetes and Alzheimer\u2019s Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?"],"prefix":"10.3390","volume":"10","author":[{"given":"Maria Assunta","family":"Potenza","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, Medical School, University of Bari \u201cAldo Moro\u201d, Polyclinic University Hospital of Bari, p.zza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Sgarra","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, Medical School, University of Bari \u201cAldo Moro\u201d, Polyclinic University Hospital of Bari, p.zza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1942-2601","authenticated-orcid":false,"given":"Vanessa","family":"Desantis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, Medical School, University of Bari \u201cAldo Moro\u201d, Polyclinic University Hospital of Bari, p.zza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Nacci","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, Medical School, University of Bari \u201cAldo Moro\u201d, Polyclinic University Hospital of Bari, p.zza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5697-8185","authenticated-orcid":false,"given":"Monica","family":"Montagnani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology-Section of Pharmacology, Medical School, University of Bari \u201cAldo Moro\u201d, Polyclinic University Hospital of Bari, p.zza G. 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Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2337\/db16-0806","article-title":"Differentiation of diabetes by pathophysiology, natural history, and prognosis","volume":"66","author":"Skyler","year":"2017","journal-title":"Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.neurobiolaging.2013.09.033","article-title":"Impaired glycemia increases disease progression in mild cognitive impairment","volume":"35","author":"Morris","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100944","DOI":"10.1016\/j.arr.2019.100944","article-title":"Diabetes mellitus and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 144 prospective studies","volume":"55","author":"Xue","year":"2019","journal-title":"Ageing Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1212\/WNL.0b013e3181eee25f","article-title":"Insulin resistance is associated with the pathology of Alzheimer disease: The Hisayama study","volume":"75","author":"Matsuzaki","year":"2010","journal-title":"Neurology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1056\/NEJMoa1215740","article-title":"Glucose levels and risk of dementia","volume":"369","author":"Crane","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E1171","DOI":"10.1152\/ajpendo.00038.2012","article-title":"Determinants of evolving metabolic and cardiovascular benefit\/risk profiles of rosiglitazone therapy during the natural history of diabetes: Molecular mechanisms in the context of integrated pathophysiology","volume":"302","author":"Sgarra","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.bbadis.2008.10.014","article-title":"Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer\u2019s disease","volume":"1792","author":"Zhao","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13195-015-0130-5","article-title":"The impact of diabetes on cognitive decline: Potential vascular, metabolic, and psychosocial risk factors","volume":"7","author":"Feinkohl","year":"2015","journal-title":"Alzheimers Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.bbadis.2008.12.003","article-title":"(Pre)diabetes, brain aging, and cognition","volume":"1792","author":"Rosset","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.bcp.2013.12.024","article-title":"Alzheimer disease: Epidemiology, diagnostic criteria, risk factors and biomarkers","volume":"88","author":"Reitz","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1212\/WNL.0b013e31828726f5","article-title":"A. Alzheimer disease in the United States (2010\u20132050) estimated using the 2010 census","volume":"80","author":"Hebert","year":"2013","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1159\/000455127","article-title":"Neuropsychiatric symptoms in Alzheimer disease, vascular dementia, and mixed dementia","volume":"17","author":"Anor","year":"2017","journal-title":"Neurodegener. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJMra0909142","article-title":"Alzheimer\u2019s disease","volume":"362","author":"Querfurth","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"a004457","DOI":"10.1101\/cshperspect.a004457","article-title":"Alzheimer\u2019s disease","volume":"3","author":"Selkoe","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wright, A.L., Zinn, R., Hohensinn, B., Konen, L.M., Beynon, S.B., Tan, R.P., Clark, I.A., Abdipranoto, A., and Vissel, B. (2013). Neuroinflammation and neuronal loss precede Abeta plaque deposition in the hAPP-J20 mouse model of Alzheimer\u2019s disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059586"},{"key":"ref_19","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-1 dysregulation, and cognitive decline","volume":"122","author":"Talbot","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_20","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":"Wands","year":"2008","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_21","first-page":"373","article-title":"The relationship between Alzheimer\u2019s disease and diabetes: Type 3 diabetes?","volume":"14","author":"Kroner","year":"2009","journal-title":"Altern. Med. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.4103\/1673-5374.238608","article-title":"Distinguishing normal brain aging from the development of Alzheimer\u2019s disease: Inflammation, insulin signaling and cognition","volume":"13","author":"Denver","year":"2018","journal-title":"Neural Regen Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1172\/JCI64595","article-title":"Alzheimer\u2019s disease and insulin resistance: Translating basic science into clinical applications","volume":"123","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fnins.2015.00204","article-title":"Aberrant insulin signaling in Alzheimer\u2019s disease: Current knowledge","volume":"9","author":"Bedse","year":"2015","journal-title":"Front. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.bbr.2016.10.033","article-title":"Lixisenatide attenuates the detrimental effects of amyloid beta protein on spatial working memory and hippocampal neurons in rats","volume":"318","author":"Cai","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_26","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 Bio."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1089\/ars.2010.3286","article-title":"Mitochondrial dynamics in diabetes","volume":"14","author":"Yoon","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7036","DOI":"10.1073\/pnas.1000645107","article-title":"Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes","volume":"107","author":"Takeda","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.mito.2014.09.005","article-title":"Potential roles of PINK1 for increased PGC-1alpha-mediated mitochondrial fatty acid oxidation and their associations with Alzheimer disease and diabetes","volume":"18","author":"Choi","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1161\/HYPERTENSIONAHA.109.130054","article-title":"Mitochondria and reactive oxygen species","volume":"53","author":"Addabbo","year":"2009","journal-title":"Hypertension"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jns.2007.01.017","article-title":"Brain mitochondrial dysfunction as a link between Alzheimer\u2019s disease and diabetes","volume":"257","author":"Moreira","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/cvr\/cvn104","article-title":"Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species","volume":"79","author":"Yu","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"679","DOI":"10.3233\/JAD-160532","article-title":"Antioxidants rescue mitochondrial transport in differentiated Alzheimer\u2019s disease trans-mitochondrial cybrid cells","volume":"54","author":"Yu","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1016\/j.freeradbiomed.2009.02.018","article-title":"Inhibition of gamma-secretase activity reduces Abeta production, reduces oxidative stress, increases mitochondrial activity and leads to reduced vulnerability to apoptosis: Implications for the treatment of Alzheimer\u2019s disease","volume":"46","author":"Sheng","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s40473-019-00179-0","article-title":"Mitochondrial dysfunction in Alzheimer\u2019s disease and progress in mitochondria-targeted therapeutics","volume":"6","author":"Flannery","year":"2019","journal-title":"Curr. Behav. Neurosci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"421","DOI":"10.3233\/JAD-161192","article-title":"The link between type 2 diabetes and neurodegeneration: Roles for amyloid-beta, amylin, and tau Proteins","volume":"59","author":"Bharadwaj","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.bbr.2017.11.015","article-title":"Diabetes mellitus and Alzheimer\u2019s disease: GSK-3beta as a potential link","volume":"339","author":"Zhang","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1111\/j.1471-4159.2007.05194.x","article-title":"The GSK3 hypothesis of Alzheimer\u2019s disease","volume":"104","author":"Hooper","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_39","first-page":"19","article-title":"Insulin and insulin resistance","volume":"26","author":"Wilcox","year":"2005","journal-title":"Clin. Biochem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.molmet.2016.06.011","article-title":"Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood","volume":"5","author":"Lee","year":"2016","journal-title":"Mol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20082102","article-title":"Insulin\/IGF-like signalling, the central nervous system and aging","volume":"418","author":"Broughton","year":"2009","journal-title":"Biochem. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0304-3940(86)90430-1","article-title":"Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography","volume":"70","author":"Corp","year":"1986","journal-title":"Neurosci. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1210\/endo-121-4-1562","article-title":"Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry","volume":"121","author":"Werther","year":"1987","journal-title":"Endocrinology"},{"key":"ref_44","first-page":"102","article-title":"Insulin and the brain","volume":"9","author":"Derakhshan","year":"2013","journal-title":"Curr. Diabetes Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"795","DOI":"10.2174\/1381612033455323","article-title":"Insulin and the blood-brain barrier","volume":"9","author":"Woods","year":"2003","journal-title":"Curr. Pharm. Des."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ijpharm.2015.12.058","article-title":"Communication from the periphery to the hypothalamus through the blood-brain barrier: An in vitro platform","volume":"499","author":"Martins","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.pharmthera.2012.07.006","article-title":"Insulin in the brain: There and back again","volume":"136","author":"Banks","year":"2012","journal-title":"Pharmacol Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11892-016-0775-x","article-title":"Diabetes and cognitive impairment","volume":"16","author":"Zilliox","year":"2016","journal-title":"Curr. Diab. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1111\/j.1476-5381.2012.01971.x","article-title":"Neuroprotective and neurotrophic actions of glucagon-like peptide-1: An emerging opportunity to treat neurodegenerative and cerebrovascular disorders","volume":"166","author":"Salcedo","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fendo.2015.00013","article-title":"Insulin, aging, and the brain: Mechanisms and implications","volume":"6","author":"Akintola","year":"2015","journal-title":"Front. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ecl.2013.09.006","article-title":"Relationships between diabetes and cognitive impairment","volume":"43","year":"2014","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Burillo, J., Marques, P., Jimenez, B., Gonzalez-Blanco, C., Benito, M., and Guillen, C. (2021). Insulin resistance and diabetes mellitus in Alzheimer\u2019s disease. Cells, 10.","DOI":"10.3390\/cells10051236"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S1474-4422(14)70249-2","article-title":"Cognitive function in patients with diabetes mellitus: Guidance for daily care","volume":"14","author":"Koekkoek","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3233\/JAD-190764","article-title":"Vascular risk factors and Alzheimer\u2019s disease: Blood-brain barrier disruption, metabolic syndromes, and molecular links","volume":"73","author":"He","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"E568","DOI":"10.1152\/ajpendo.00297.2009","article-title":"Vascular actions of insulin with implications for endothelial dysfunction","volume":"297","author":"Potenza","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.2174\/092986711795496755","article-title":"Cardiovascular complications in diabetes: Lessons from animal models","volume":"18","author":"Potenza","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3233\/JAD-2005-7107","article-title":"Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer\u2019s disease\u2014Is this type 3 diabetes?","volume":"7","author":"Steen","year":"2005","journal-title":"J. Alzheimers Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.jalz.2015.12.006","article-title":"Diabetes is associated with cerebrovascular but not Alzheimer\u2019s disease neuropathology","volume":"12","author":"Abner","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/bpa.12655","article-title":"Alzheimer\u2019s disease and type 2 diabetes mellitus are distinct diseases with potential overlapping metabolic dysfunction upstream of observed cognitive decline","volume":"29","author":"Chornenkyy","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1159\/000348407","article-title":"Subgroups of Alzheimer\u2019s disease associated with diabetes mellitus based on brain imaging","volume":"35","author":"Fukazawa","year":"2013","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/med.21440","article-title":"Bridging type 2 diabetes and Alzheimer\u2019s disease: Assembling the puzzle pieces in the quest for the molecules with therapeutic and preventive potential","volume":"38","author":"Rauter","year":"2018","journal-title":"Med. Res. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev.biochem.75.101304.123901","article-title":"Protein misfolding, functional amyloid, and human disease","volume":"75","author":"Chiti","year":"2006","journal-title":"Ann. Rev. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.ajpath.2014.11.016","article-title":"In vivo seeding and cross-seeding of localized amyloidosis: A molecular link between type 2 diabetes and Alzheimer disease","volume":"185","author":"Oskarsson","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5409","DOI":"10.1096\/fj.201700431R","article-title":"Amyloid-beta and islet amyloid pathologies link Alzheimer\u2019s disease and type 2 diabetes in a transgenic model","volume":"31","author":"Wijesekara","year":"2017","journal-title":"FASEB J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1056\/NEJMc0802893","article-title":"Widespread amyloid deposition in transplanted human pancreatic islets","volume":"359","author":"Westermark","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s00125-008-1255-x","article-title":"Oxidative stress is induced by islet amyloid formation and time-dependently mediates amyloid-induced beta cell apoptosis","volume":"52","author":"Zraika","year":"2009","journal-title":"Diabetologia"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/ana.23956","article-title":"Amylin deposition in the brain: A second amyloid in Alzheimer disease?","volume":"74","author":"Jackson","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"928","DOI":"10.2174\/1567205011666141107124538","article-title":"Islet Amyloid Polypeptide (IAPP): A second amyloid in Alzheimer\u2019s disease","volume":"11","author":"Fawver","year":"2014","journal-title":"Curr. Alzheimer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/S0006-291X(88)80538-2","article-title":"Amyloid fibrils formed from a segment of the pancreatic islet amyloid protein","volume":"155","author":"Glenner","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrn2168","article-title":"Intracellular amyloid-beta in Alzheimer\u2019s disease","volume":"8","author":"LaFerla","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1080\/07853890.2016.1197416","article-title":"Insulin-degrading enzyme: New therapeutic target for diabetes and Alzheimer\u2019s disease?","volume":"48","author":"Pivovarova","year":"2016","journal-title":"Ann. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e12684","DOI":"10.1111\/acel.12684","article-title":"Amyloid Beta monomers regulate cyclic adenosine monophosphate response element binding protein functions by activating type-1 insulin-like growth factor receptors in neuronal cells","volume":"17","author":"Zimbone","year":"2018","journal-title":"Aging Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1096\/fj.03-0978fje","article-title":"Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer\u2019s disease","volume":"18","author":"Ho","year":"2004","journal-title":"FASEB J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fnagi.2017.00118","article-title":"Insulin resistance as a link between amyloid-beta and tau pathologies in Alzheimer\u2019s disease","volume":"9","author":"Mullins","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"RC221","DOI":"10.1523\/JNEUROSCI.22-10-j0001.2002","article-title":"Alzheimer\u2019s beta-amyloid peptides compete for insulin binding to the insulin receptor","volume":"22","author":"Xie","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1096\/fj.06-7703com","article-title":"Amyloid beta oligomers induce impairment of neuronal insulin receptors","volume":"22","author":"Zhao","year":"2008","journal-title":"FASEB J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1172\/JCI57256","article-title":"An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer\u2019s disease- associated Abeta oligomers","volume":"122","author":"Bomfim","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.neuroscience.2013.01.075","article-title":"Okadaic acid-induced Tau phosphorylation in rat brain: Role of NMDA receptor","volume":"238","author":"Kamat","year":"2013","journal-title":"Neuroscience"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"F1000","DOI":"10.12688\/f1000research.10557.1","article-title":"Recent advances in understanding the cellular roles of GSK-3","volume":"6","author":"Cormier","year":"2017","journal-title":"F1000Research"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.2174\/1389450110607011435","article-title":"Role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes","volume":"7","author":"Henriksen","year":"2006","journal-title":"Curr. Drug Targets"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"19929","DOI":"10.1074\/jbc.273.32.19929","article-title":"Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase\/Akt cell survival pathway","volume":"273","author":"Pap","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8602","DOI":"10.1038\/s41598-017-09239-5","article-title":"In vivo regulation of glycogen synthase kinase 3beta activity in neurons and brains","volume":"7","author":"Krishnankutty","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"33435","DOI":"10.1074\/jbc.M110.149419","article-title":"Spectroscopic studies of GSK3{beta} phosphorylation of the neuronal tau protein and its interaction with the N-terminal domain of apolipoprotein E","volume":"285","author":"Leroy","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"S141","DOI":"10.3233\/JAD-2012-129025","article-title":"GSK3 and tau: Two convergence points in Alzheimer\u2019s disease","volume":"33","author":"Hernandez","year":"2013","journal-title":"J. Alzheimers Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/path.2912","article-title":"Deficient brain insulin signalling pathway in Alzheimer\u2019s disease and diabetes","volume":"225","author":"Liu","year":"2011","journal-title":"J. Pathol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.nbd.2008.10.007","article-title":"GSK3 inhibitors show benefits in an Alzheimer\u2019s Disease (AD) model of neurodegeneration but adverse effects in control animals","volume":"33","author":"Hu","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.it.2007.04.005","article-title":"Complexities of targeting innate immunity to treat infection","volume":"28","author":"Brown","year":"2007","journal-title":"Trends Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrd4275","article-title":"Targeting inflammation in the treatment of type 2 diabetes: Time to start","volume":"13","author":"Donath","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nrn3880","article-title":"Immune attack: The role of inflammation in Alzheimer disease","volume":"16","author":"Heppner","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.phrs.2017.04.009","article-title":"Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options","volume":"120","author":"Potenza","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/jcb.24402","article-title":"Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus","volume":"114","author":"Akash","year":"2013","journal-title":"J. Cell Biochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1172\/JCI200319451","article-title":"Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance","volume":"112","author":"Xu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"973","DOI":"10.2174\/1381612053381684","article-title":"Blood-brain barrier transport of cytokines: A mechanism for neuropathology","volume":"11","author":"Banks","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/cvr\/cvt336","article-title":"Elastin-derived peptides potentiate atherosclerosis through the immune Neu1-PI3Kgamma pathway","volume":"102","author":"Gayral","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"345","DOI":"10.5114\/ceji.2014.45946","article-title":"Abnormal levels of age-elastin derived peptides in sera of diabetic patients with arterial hypertension","volume":"39","author":"Nikolov","year":"2014","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.2174\/1381612824666180327170632","article-title":"The Role of Inflammation in Neurological Disorders","volume":"24","author":"Degan","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.2337\/db13-0508","article-title":"Elastin-derived peptides are new regulators of insulin resistance development in mice","volume":"62","author":"Blaise","year":"2013","journal-title":"Diabetes"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1007\/s12035-016-9833-2","article-title":"Metabolic and inflammatory adaptation of reactive astrocytes: Role of PPARs","volume":"54","author":"Iglesias","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s12640-019-00114-x","article-title":"The elastin-derived peptide VGVAPG does not activate the inflammatory process in mouse cortical astrocytes in vitro","volume":"37","author":"Szychowski","year":"2020","journal-title":"Neurotox. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"H1850","DOI":"10.1152\/ajpheart.01199.2008","article-title":"Feed-forward signaling of TNF-alpha and NF-kappaB via IKK-beta pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice","volume":"296","author":"Yang","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"pe47","DOI":"10.1126\/scisignal.2003511","article-title":"PKR-dependent inflammatory signals","volume":"5","author":"Kang","year":"2012","journal-title":"Sci. Signal."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cmet.2013.11.002","article-title":"TNF-alpha mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer\u2019s beta-amyloid oligomers in mice and monkeys","volume":"18","author":"Lourenco","year":"2013","journal-title":"Cell Metab."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.2174\/138161206777947470","article-title":"Inflamm-aging, cytokines and aging: State of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology","volume":"12","author":"Salvioli","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_105","first-page":"756357","article-title":"A review: Inflammatory process in Alzheimer\u2019s disease, role of cytokines","volume":"2012","year":"2012","journal-title":"Sci. World J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0197-4580(00)00124-X","article-title":"Inflammation and Alzheimer\u2019s disease","volume":"21","author":"Akiyama","year":"2000","journal-title":"Neurobiol. Aging"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e789","DOI":"10.1038\/cddis.2013.325","article-title":"Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis","volume":"4","author":"Azevedo","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.cellsig.2010.01.010","article-title":"Tumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction","volume":"22","author":"Park","year":"2010","journal-title":"Cell Signal."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"531","DOI":"10.2174\/156720509790147070","article-title":"Amyloid deposition and inflammation in APPswe\/PS1dE9 mouse model of Alzheimer\u2019s disease","volume":"6","author":"Ruan","year":"2009","journal-title":"Curr. Alzheimer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1358\/dof.2020.45.2.3071567","article-title":"Alzheimer\u2019s disease murine models: Focus on late-onset disease","volume":"45","author":"Potenza","year":"2020","journal-title":"Drugs Future"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.2353\/ajpath.2009.080814","article-title":"The unfolded protein response is activated in pretangle neurons in Alzheimer\u2019s disease hippocampus","volume":"174","author":"Hoozemans","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.imlet.2008.02.002","article-title":"Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer\u2019s disease","volume":"117","author":"Bermejo","year":"2008","journal-title":"Immunol. Lett."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1212\/01.wnl.0000263217.36439.da","article-title":"Inflammatory markers and the risk of Alzheimer disease: The Framingham Study","volume":"68","author":"Tan","year":"2007","journal-title":"Neurology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/35041687","article-title":"Oxidants, oxidative stress and the biology of ageing","volume":"408","author":"Finkel","year":"2000","journal-title":"Nature"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.cmet.2009.08.009","article-title":"Reactive oxygen species enhance insulin sensitivity","volume":"10","author":"Loh","year":"2009","journal-title":"Cell Metab."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.arr.2004.05.002","article-title":"Reactive oxygen species and synaptic plasticity in the aging hippocampus","volume":"3","author":"Serrano","year":"2004","journal-title":"Ageing Res. Rev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.nbd.2015.04.020","article-title":"Oxidative and nitrative stress in neurodegeneration","volume":"84","author":"Cobb","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"S125","DOI":"10.3233\/JAD-132738","article-title":"Apoptosis and oxidative stress in neurodegenerative diseases","volume":"42","author":"Radi","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.brainres.2007.02.084","article-title":"Elevated levels of 3-nitrotyrosine in brain from subjects with amnestic mild cognitive impairment: Implications for the role of nitration in the progression of Alzheimer\u2019s disease","volume":"1148","author":"Butterfield","year":"2007","journal-title":"Brain Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3233\/JAD-2009-1013","article-title":"Oxidative stress in diabetes and Alzheimer\u2019s disease","volume":"16","author":"Reddy","year":"2009","journal-title":"J. Alzheimers Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.neuropharm.2017.11.027","article-title":"Impaired peripheral glucose homeostasis and Alzheimer\u2019s disease","volume":"136","author":"Wijesekara","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1016\/j.bbadis.2015.08.001","article-title":"Oxidative stress, mitochondrial damage and diabetic retinopathy","volume":"1852","author":"Kowluru","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/dmrr.2718","article-title":"Oxidative stress, type 2 diabetes and vitamin D: Past, present and future","volume":"32","author":"Nikooyeh","year":"2015","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"302682","DOI":"10.1155\/2012\/302682","article-title":"Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan-induced diabetic rats","volume":"2012","author":"Ceretta","year":"2012","journal-title":"Exp. Diabetes Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s11064-011-0588-x","article-title":"Protection by DHA of early hippocampal changes in diabetes: Possible role of CREB and NF-kappaB","volume":"37","author":"Arnal","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"44557","DOI":"10.1074\/jbc.M111.279208","article-title":"SOD1 (copper\/zinc superoxide dismutase) deficiency drives amyloid beta protein oligomerization and memory loss in mouse model of Alzheimer disease","volume":"286","author":"Murakami","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.bbadis.2013.10.015","article-title":"Oxidative stress and mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"1842","author":"Wang","year":"2014","journal-title":"Biochim. Biophys Acta"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s12017-011-8155-9","article-title":"Oxidative stress and beta-amyloid protein in Alzheimer\u2019s disease","volume":"13","author":"Cai","year":"2011","journal-title":"Neuromolecular Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.neurobiolaging.2008.07.003","article-title":"Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer\u2019s disease","volume":"31","author":"Jo","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1002\/jnr.22271","article-title":"Oxidative stress up-regulates presenilin 1 in lipid rafts in neuronal cells","volume":"88","author":"Oda","year":"2010","journal-title":"J. Neurosci. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/s12640-011-9283-6","article-title":"Amyloid-beta production: Major link between oxidative stress and BACE1","volume":"22","author":"Tamagno","year":"2012","journal-title":"Neurotox. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1007\/s00415-011-6104-z","article-title":"The role of mitochondria in neurodegenerative diseases","volume":"258","author":"Filosto","year":"2011","journal-title":"J. Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nature05292","article-title":"Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases","volume":"443","author":"Lin","year":"2006","journal-title":"Nature"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fnagi.2013.00053","article-title":"Sirtuins in neurodegenerative diseases: An update on potential mechanisms","volume":"5","author":"Min","year":"2013","journal-title":"Front. Aging Neurosci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/cr.2013.70","article-title":"Sirtuin deacetylases in neurodegenerative diseases of aging","volume":"23","author":"Herskovits","year":"2013","journal-title":"Cell Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1007\/s11064-016-2110-y","article-title":"Sirtuins and their roles in brain aging and neurodegenerative disorders","volume":"42","author":"Jesko","year":"2016","journal-title":"Neurochem, Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.tins.2017.01.002","article-title":"Mitophagy and Alzheimer\u2019s disease: Cellular and molecular mechanisms","volume":"40","author":"Kerr","year":"2017","journal-title":"Trends Neurosci."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Kong, X., Wang, R., Xue, Y., Liu, X., Zhang, H., Chen, Y., Fang, F., and Chang, Y. (2010). Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011707"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.cmet.2015.10.013","article-title":"Mitochondrial SIRT3 mediates adaptive responses of neurons to exercise and metabolic and excitatory challenges","volume":"23","author":"Cheng","year":"2016","journal-title":"Cell Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.neurobiolaging.2012.11.020","article-title":"Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: Evidence for improved neuronal bioenergetics and autophagy procession","volume":"34","author":"Liu","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"R169","DOI":"10.1093\/hmg\/ddp326","article-title":"Mitochondrial dynamics\u2014Fusion, fission, movement, and mitophagy\u2014In neurodegenerative diseases","volume":"18","author":"Chen","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.2337\/db14-0758","article-title":"Drp1-mediated mitochondrial abnormalities link to synaptic injury in diabetes model","volume":"64","author":"Huang","year":"2015","journal-title":"Diabetes"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/cns.12655","article-title":"Mitochondrial dysfunction and biogenesis in neurodegenerative diseases: Pathogenesis and treatment","volume":"23","author":"Golpich","year":"2017","journal-title":"CNS Neurosci. Ther."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/ajmg.1425","article-title":"Mitochondria and degenerative disorders","volume":"106","author":"Orth","year":"2001","journal-title":"Am. J. Med. Genet."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"18725","DOI":"10.1038\/srep18725","article-title":"Altered brain energetics induces mitochondrial fission arrest in Alzheimer\u2019s Disease","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1046\/j.1471-4159.1994.63062179.x","article-title":"Cortical cytochrome oxidase activity is reduced in Alzheimer\u2019s disease","volume":"63","author":"Mutisya","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_147","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":"ref_148","doi-asserted-by":"crossref","first-page":"8972","DOI":"10.1523\/JNEUROSCI.20-24-08972.2000","article-title":"Inhibition of Krebs cycle enzymes by hydrogen peroxide: A key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress","volume":"20","author":"Tretter","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1089\/ars.2011.4277","article-title":"Synaptic mitochondrial pathology in Alzheimer\u2019s disease","volume":"16","author":"Du","year":"2012","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Wang, L., Guo, L., Lu, L., Sun, H., Shao, M., Beck, S.J., Li, L., Ramachandran, J., Du, Y., and Du, H. (2016). Synaptosomal mitochondrial dysfunction in 5xFAD mouse model of Alzheimer\u2019s disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150441"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1046\/j.0022-3042.2001.00681.x","article-title":"Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities","volume":"80","author":"Casley","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1046\/j.1471-4159.2001.00112.x","article-title":"Neurotoxic Abeta peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxide-synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro","volume":"76","author":"Parks","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1038\/nm1008-1020","article-title":"Portal to Alzheimer\u2019s disease","volume":"14","author":"Starkov","year":"2008","journal-title":"Nat. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ceca.2009.12.014","article-title":"The dysregulation of intracellular calcium in Alzheimer disease","volume":"47","author":"Supnet","year":"2010","journal-title":"Cell Calcium"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1111\/bph.14585","article-title":"Mitochondrial dysfunction in Alzheimer\u2019s disease: Role in pathogenesis and novel therapeutic opportunities","volume":"176","author":"Swerdlow","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_156","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\u2019s disease","volume":"120","author":"Sheng","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1023\/A:1010955807739","article-title":"Mitochondrial involvement in brain function and dysfunction: Relevance to aging, neurodegenerative disorders and longevity","volume":"26","author":"Calabrese","year":"2001","journal-title":"Neurochem. Res."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Ke, Y.D., Delerue, F., Gladbach, A., Gotz, J., and Ittner, L.M. (2009). Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer\u2019s disease. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007917"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nn2055","article-title":"Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons","volume":"11","author":"Stranahan","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.neurobiolaging.2008.02.010","article-title":"The pathological interaction between diabetes and presymptomatic Alzheimer\u2019s disease","volume":"30","author":"Burdo","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1073\/pnas.0511154103","article-title":"Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology","volume":"103","author":"Yu","year":"2006","journal-title":"Proc. Natl. Acad. Sci USA"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.2337\/db11-1640","article-title":"Transgenic control of mitochondrial fission induces mitochondrial uncoupling and relieves diabetic oxidative stress","volume":"61","author":"Galloway","year":"2012","journal-title":"Diabetes"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/gerona\/gly198","article-title":"The rat prefrontal-cortex transcriptome: Effects of aging and sporadic Alzheimer\u2019s disease-like pathology","volume":"74","author":"Stefanova","year":"2019","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3233\/JAD-180065","article-title":"Mitochondrial Dysfunction as a Predictor and Driver of Alzheimer\u2019s Disease-Like Pathology in OXYS Rats","volume":"63","author":"Tyumentsev","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s11011-014-9631-3","article-title":"Role of insulin resistance in Alzheimer\u2019s disease","volume":"30","author":"Cai","year":"2015","journal-title":"Metab. Brain Dis."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1007\/s10571-016-0434-4","article-title":"Relationship between beta-amyloid and mitochondrial dynamics","volume":"37","author":"Kim","year":"2017","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.mam.2015.01.004","article-title":"Mitochondrial regulation of beta-cell function: Maintaining the momentum for insulin release","volume":"42","author":"Kaufman","year":"2015","journal-title":"Mol. Aspects Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.2337\/diabetes.51.10.2944","article-title":"Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes","volume":"51","author":"Kelley","year":"2002","journal-title":"Diabetes"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.cmet.2010.04.004","article-title":"Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease PARL","volume":"11","author":"Civitarese","year":"2011","journal-title":"Cell Metab."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"17075","DOI":"10.1073\/pnas.0707060104","article-title":"Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance","volume":"104","author":"Zhang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Petersen, K.F., Dufour, S., and Shulman, G.I. (2005). Decreased insulin-stimulated ATP synthesis and phosphate transport in muscle of insulin-resistant offspring of type 2 diabetic parents. PLoS Med., 2.","DOI":"10.1371\/journal.pmed.0020233"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.2337\/db06-0783","article-title":"Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients","volume":"56","author":"Befroy","year":"2007","journal-title":"Diabetes"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1016\/j.freeradbiomed.2009.08.014","article-title":"Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: Role of p38 MAPK","volume":"47","author":"Archuleta","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.bbagrm.2011.10.011","article-title":"Nucleus-encoded regulators of mitochondrial function: Integration of respiratory chain expression, nutrient sensing and metabolic stress","volume":"1819","author":"Scarpulla","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3109\/10715760903494168","article-title":"Oxidative damage of mitochondrial DNA in diabetes and its protection by manganese superoxide dismutase","volume":"44","author":"Zhong","year":"2010","journal-title":"Free Radic Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1056\/NEJMoa031314","article-title":"Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes","volume":"350","author":"Petersen","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1507\/endocrj.EJ11-0099","article-title":"Functional loss of Cdkal1, a novel tRNA modification enzyme, causes the development of type 2 diabetes","volume":"58","author":"Wei","year":"2011","journal-title":"Endocr. J."},{"key":"ref_178","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. Alzheimers Dis."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fnins.2018.00025","article-title":"Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer\u2019s disease","volume":"12","author":"Kametani","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/nm.2460","article-title":"Resolving controversies on the path to Alzheimer\u2019s therapeutics","volume":"17","author":"Selkoe","year":"2011","journal-title":"Nat. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S1474-4422(19)30480-6","article-title":"A resurrection of aducanumab for Alzheimer\u2019s disease","volume":"19","author":"Schneider","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41582-019-0205-1","article-title":"Alzheimer disease and aducanumab: Adjusting our approach","volume":"15","author":"Selkoe","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41582-019-0295-9","article-title":"Questions EMERGE as Biogen claims aducanumab turnaround","volume":"16","author":"Howard","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1055\/s-0039-1678581","article-title":"Current and future treatments in Alzheimer\u2019s disease","volume":"39","author":"Atri","year":"2019","journal-title":"Semin. Neurol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3389\/fphar.2020.00261","article-title":"Pharmacotherapy of Alzheimer\u2019s disease: Seeking clarity in a time of uncertainty","volume":"11","author":"Yahaya","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"173554","DOI":"10.1016\/j.ejphar.2020.173554","article-title":"Alzheimer\u2019s disease: Recent treatment strategies","volume":"887","author":"Vaz","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.neurobiolaging.2012.11.023","article-title":"A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer\u2019s disease","volume":"34","author":"Kashiwaya","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1111\/jnc.13868","article-title":"3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons","volume":"139","author":"Marosi","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_189","first-page":"28","article-title":"Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer\u2019s disease","volume":"4","author":"Taylor","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Rusek, M., Pluta, R., Ulamek-Koziol, M., and Czuczwar, S.J. (2019). Ketogenic diet in Alzheimer\u2019s disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20163892"},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Tumminia, A., Vinciguerra, F., Parisi, M., and Frittitta, L. (2016). Type 2 diabetes mellitus and Alzheimer\u2019s disease: Role of insulin signaling and therapeutic implications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113306"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ejphar.2004.02.045","article-title":"Insulin and the insulin receptor in experimental models of learning and memory","volume":"490","author":"Zhao","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0303-7207(01)00455-5","article-title":"Role of insulin and insulin receptor in learning and memory","volume":"177","author":"Zhao","year":"2001","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1037\/a0017722","article-title":"Intracerebroventricular insulin improves spatial learning and memory in male Wistar rats","volume":"123","author":"Mohaddes","year":"2009","journal-title":"Behav. Neurosci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nrn3209","article-title":"The many faces of insulin-like peptide signaling in the brain","volume":"13","author":"Fernandez","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"488","DOI":"10.2337\/dc11-2075","article-title":"Impaired insulin sensitivity as indexed by the HOMA score is associated with deficits in verbal fluency and temporal lobe gray matter volume in the elderly","volume":"35","author":"Benedict","year":"2012","journal-title":"Diabetes Care"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.exger.2010.08.026","article-title":"Intranasal insulin as a therapeutic option in the treatment of cognitive impairments","volume":"46","author":"Benedict","year":"2011","journal-title":"Exp. Gerontol."},{"key":"ref_198","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":"ref_199","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s40263-013-0076-8","article-title":"Intranasal insulin as a treatment for Alzheimer\u2019s disease: A review of basic research and clinical evidence","volume":"27","author":"Freiherr","year":"2013","journal-title":"CNS Drugs"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.neurobiolaging.2005.03.016","article-title":"Effects of intranasal insulin on cognition in memory-impaired older adults: Modulation by APOE genotype","volume":"27","author":"Reger","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"428","DOI":"10.2337\/dc09-1499","article-title":"Incretin-based therapies for the treatment of type 2 diabetes: Evaluation of the risks and benefits","volume":"33","author":"Drucker","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"104707","DOI":"10.1016\/j.neuint.2020.104707","article-title":"Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer\u2019s disease","volume":"135","author":"Akhtar","year":"2020","journal-title":"Neurochem. Int."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/01616412.2016.1145914","article-title":"Liraglutide prevents beta-amyloid-induced neurotoxicity in SH-SY5Y cells via a PI3K-dependent signaling pathway","volume":"38","author":"Liu","year":"2016","journal-title":"Neurol. Res."},{"key":"ref_204","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":"ref_205","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2174\/156720507780362092","article-title":"Therapeutic use of agonists of the nuclear receptor PPARgamma in Alzheimer\u2019s disease","volume":"4","author":"Landreth","year":"2007","journal-title":"Curr. Alzheimer Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1073\/pnas.0809158106","article-title":"Protection of synapses against Alzheimer\u2019s-linked toxins: Insulin signaling prevents the pathogenic binding of Abeta oligomers","volume":"106","author":"Vieira","year":"2009","journal-title":"Proc. Natl. Acad. Sci USA"},{"key":"ref_207","first-page":"246","article-title":"Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer\u2019s disease","volume":"6","author":"Risner","year":"2006","journal-title":"Pharm. J."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.neubiorev.2016.03.005","article-title":"Diabetes and Alzheimer\u2019s disease crosstalk","volume":"64","author":"Shi","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"592","DOI":"10.2174\/156720511796391935","article-title":"Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer\u2019s disease: Two phase 3 studies","volume":"8","author":"Harrington","year":"2011","journal-title":"Curr. Alzheimer Res."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.3233\/JAD-2010-100939","article-title":"A multi-center randomized proof-of-concept clinical trial applying [(1)(8)F]FDG-PET for evaluation of metabolic therapy with rosiglitazone XR in mild to moderate Alzheimer\u2019s disease","volume":"22","author":"Tzimopoulou","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"l7078","DOI":"10.1136\/bmj.l7078","article-title":"Updating insights into rosiglitazone and cardiovascular risk through shared data: Individual patient and summary level meta-analyses","volume":"368","author":"Wallach","year":"2020","journal-title":"BMJ"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1093\/brain\/awh452","article-title":"Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice","volume":"128","author":"Heneka","year":"2005","journal-title":"Brain"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00702-014-1294-z","article-title":"Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice","volume":"122","author":"Yu","year":"2015","journal-title":"J. Neural Transm."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1016\/j.neurobiolaging.2009.10.009","article-title":"Efficacy of PPAR-gamma agonist pioglitazone in mild Alzheimer disease","volume":"32","author":"Sato","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1532-5415.2009.02067.x","article-title":"Pioglitazone improved cognition in a pilot study on patients with Alzheimer\u2019s disease and mild cognitive impairment with diabetes mellitus","volume":"57","author":"Hanyu","year":"2009","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1111\/j.1532-5415.2010.02841.x","article-title":"The role of tumor necrosis factor-alpha in cognitive improvement after peroxisome proliferator-activator receptor gamma agonist pioglitazone treatment in Alzheimer\u2019s disease","volume":"58","author":"Hanyu","year":"2010","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/dom.13373","article-title":"Comparative efficacy and acceptability of antidiabetic agents for Alzheimer\u2019s disease and mild cognitive impairment: A systematic review and network meta-analysis","volume":"20","author":"Cao","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000371509","article-title":"Effects of pioglitazone or exercise in older adults with mild cognitive impairment and insulin resistance: A pilot study","volume":"5","author":"Hildreth","year":"2015","journal-title":"Dement. Geriatr. Cogn. Dis. Extra"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1001\/archneurol.2010.229","article-title":"A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease","volume":"68","author":"Geldmacher","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/ageing\/afs188","article-title":"Risk factors for dementia with type 2 diabetes mellitus among elderly people in China","volume":"42","author":"Ma","year":"2013","journal-title":"Age Ageing"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/mds.25824","article-title":"A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy","volume":"29","author":"Tolosa","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3233\/JAD-141959","article-title":"A phase II trial of tideglusib in Alzheimer\u2019s disease","volume":"45","author":"Lovestone","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1074\/jbc.M111.306472","article-title":"Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib","volume":"287","author":"Dominguez","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.nbd.2009.05.025","article-title":"A novel GSK-3beta inhibitor reduces Alzheimer\u2019s pathology and rescues neuronal loss in vivo","volume":"35","author":"Sereno","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"5766","DOI":"10.1523\/JNEUROSCI.1004-07.2007","article-title":"NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: Potential therapeutic role in brain disorders","volume":"27","author":"Martinez","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.neurobiolaging.2017.05.010","article-title":"Glucocorticoid-mediated activation of GSK3beta promotes tau phosphorylation and impairs memory in type 2 diabetes","volume":"57","author":"Dey","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s10517-021-05191-7","article-title":"Oxidative stress: Pathogenetic role in diabetes mellitus and its complications and therapeutic approaches to correction","volume":"171","author":"Darenskaya","year":"2021","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1523\/JNEUROSCI.0295-20.2020","article-title":"Oxidative damage and antioxidant response in frontal cortex of demented and nondemented individuals with Alzheimer\u2019s neuropathology","volume":"41","author":"Fracassi","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.drudis.2006.05.016","article-title":"Inhibitors of the Maillard reaction and AGE breakers as therapeutics for multiple diseases","volume":"11","author":"Reddy","year":"2006","journal-title":"Drug Discov. Today"},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Zheng, Q., Kebede, M.T., Kemeh, M.M., Islam, S., Lee, B., Bleck, S.D., Wurfl, L.A., and Lazo, N.D. (2019). Inhibition of the self-assembly of abeta and of tau by polyphenols: Mechanistic studies. Molecules, 24.","DOI":"10.3390\/molecules24122316"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"24228","DOI":"10.1074\/jbc.M110.133108","article-title":"Resveratrol selectively remodels soluble oligomers and fibrils of amyloid Abeta into off-pathway conformers","volume":"285","author":"Ladiwala","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"126","DOI":"10.2174\/1570159X15666170703113212","article-title":"Effects of resveratrol and other polyphenols on Sirt1: Relevance to brain function during aging","volume":"16","author":"Sarubbo","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"8152373","DOI":"10.1155\/2018\/8152373","article-title":"Neuroprotective mechanisms of resveratrol in Alzheimer\u2019s disease: Role of SIRT1","volume":"2018","author":"Gomes","year":"2018","journal-title":"Oxid Med. Cell Longev."},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Yang, A.J.T., Bagit, A., and MacPherson, R.E.K. (2021). Resveratrol, metabolic dysregulation, and Alzheimer\u2019s disease: Considerations for neurogenerative disease. Int J. Mol. Sci, 22.","DOI":"10.3390\/ijms22094628"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.ejmech.2015.01.047","article-title":"Resveratrol interferes with the aggregation of membrane-bound human-IAPP: A molecular dynamics study","volume":"92","author":"Lolicato","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/ptr.5501","article-title":"Effects of resveratrol on receptor for advanced glycation end products (RAGE) expression and oxidative stress in the liver of rats with type 2 diabetes","volume":"30","author":"Khazaei","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1002\/mnfr.201400933","article-title":"Resveratrol treatment restores peripheral insulin sensitivity in diabetic mice in a sirt1-independent manner","volume":"59","author":"Santamaria","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.biopha.2017.08.070","article-title":"Resveratrol and diabetes: A critical review of clinical studies","volume":"95","author":"Ozturk","year":"2017","journal-title":"Biomed. Pharm."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/s41593-018-0332-9","article-title":"Mitophagy inhibits amyloid-beta and tau pathology and reverses cognitive deficits in models of Alzheimer\u2019s disease","volume":"22","author":"Fang","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"945","DOI":"10.3233\/JAD-190123","article-title":"Resveratrol and metformin recover prefrontal cortex AMPK activation in diet-induced obese mice but reduce BDNF and synaptophysin protein content","volume":"71","author":"Yang","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1212\/WNL.0000000000002035","article-title":"A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease","volume":"85","author":"Turner","year":"2015","journal-title":"Neurology"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0779-0","article-title":"Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer\u2019s disease","volume":"14","author":"Moussa","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"899","DOI":"10.3233\/JAD-150872","article-title":"Antioxidative and neuroprotective effects of curcumin in an Alzheimer\u2019s disease rat model co-treated with intracerebroventricular streptozotocin and subcutaneous D-galactose","volume":"52","author":"Huang","year":"2016","journal-title":"J. Alzheimers Dis."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1021\/acschemneuro.5b00214","article-title":"Curcumin attenuates amyloid-beta aggregate toxicity and modulates amyloid-beta aggregation pathway","volume":"7","author":"Thapa","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1080\/14756360802364377","article-title":"Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro\/in vivo evaluation","volume":"24","author":"Bustanji","year":"2009","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1017\/S0007114515004687","article-title":"Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer\u2019s disease","volume":"115","author":"Goozee","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1017\/S0007114516001203","article-title":"Curcumin and cognition: A randomised, placebo-controlled, double-blind study of community-dwelling older adults","volume":"115","author":"Brown","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: Problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nrendo.2011.138","article-title":"The role of mitochondria in insulin resistance and type 2 diabetes mellitus","volume":"8","author":"Szendroedi","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nrd.2018.174","article-title":"Mitochondria as a therapeutic target for common pathologies","volume":"17","author":"Murphy","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_251","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":"ref_252","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/35073006","article-title":"Versatility of the mitochondrial protein import machinery","volume":"2","author":"Pfanner","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"202","DOI":"10.2174\/1874467212666181127151059","article-title":"Mitochondria-targeted drugs","volume":"12","author":"Zinovkin","year":"2018","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"e12715","DOI":"10.1111\/acel.12715","article-title":"The mitochondrial ATP synthase is a shared drug target for aging and dementia","volume":"17","author":"Goldberg","year":"2018","journal-title":"Aging Cell"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3233\/JAD-2010-100174","article-title":"Dimebon (latrepirdine) enhances mitochondrial function and protects neuronal cells from death","volume":"21","author":"Zhang","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0140-6736(08)61074-0","article-title":"Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer\u2019s disease: A randomised, double-blind, placebo-controlled study","volume":"372","author":"Doody","year":"2008","journal-title":"Lancet"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"6078","DOI":"10.1007\/s12035-015-9515-5","article-title":"Mechanisms of mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"53","author":"Cadonic","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1750-1326-9-42","article-title":"Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau\/APP mutant mice","volume":"9","author":"Yuzwa","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"15703","DOI":"10.1523\/JNEUROSCI.0552-11.2011","article-title":"The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer\u2019s disease","volume":"31","author":"McManus","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.expneurol.2005.12.026","article-title":"Effect of the mitochondrial antioxidant, Mito Vitamin E, on hypoxic-ischemic striatal injury in neonatal rats: A dose-response and stereological study","volume":"199","author":"Covey","year":"2006","journal-title":"Exp. Neurol."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymgme.2017.09.009","article-title":"Therapies for mitochondrial diseases and current clinical trials","volume":"122","author":"Zarante","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.mcn.2019.03.001","article-title":"Small molecules as therapeutic drugs for Alzheimer\u2019s disease","volume":"96","author":"Oliver","year":"2019","journal-title":"Mol. Cell Neurosci."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.devcel.2007.11.019","article-title":"Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax\/Bak-dependent mitochondrial outer membrane permeabilization","volume":"14","author":"Chipuk","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/s42255-019-0073-4","article-title":"The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans","volume":"1","author":"Andreux","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_265","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":"ref_266","doi-asserted-by":"crossref","first-page":"5099","DOI":"10.1523\/JNEUROSCI.2385-16.2017","article-title":"Inhibition of Drp1 ameliorates synaptic depression, abeta deposition, and cognitive impairment in an Alzheimer\u2019s disease model","volume":"37","author":"Baek","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"35","DOI":"10.5483\/BMBRep.2020.53.1.274","article-title":"Emerging perspectives on mitochondrial dysfunction and inflammation in Alzheimer\u2019s disease","volume":"53","author":"Yoo","year":"2020","journal-title":"BMB Rep."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1021\/acsmedchemlett.5b00451","article-title":"Identification of a small molecule cyclophilin D inhibitor for rescuing abeta-mediated mitochondrial dysfunction","volume":"7","author":"Valasani","year":"2016","journal-title":"ACS Med. Chem. Lett."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/8\/1257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:41:30Z","timestamp":1760164890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/8\/1257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,6]]},"references-count":268,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["antiox10081257"],"URL":"https:\/\/doi.org\/10.3390\/antiox10081257","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,6]]}}}