{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:49:39Z","timestamp":1787698179924,"version":"build-2784847793"},"reference-count":255,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:00Z","timestamp":1625788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS053956"],"award-info":[{"award-number":["NS053956"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Neurodegenerative disorders affect fifteen percent of the world\u2019s population and pose a significant financial burden to all nations. Cognitive impairment is the seventh leading cause of death throughout the globe. Given the enormous challenges to treat cognitive disorders, such as Alzheimer\u2019s disease, and the inability to markedly limit disease progression, circadian clock gene pathways offer an exciting strategy to address cognitive loss. Alterations in circadian clock genes can result in age-related motor deficits, affect treatment regimens with neurodegenerative disorders, and lead to the onset and progression of dementia. Interestingly, circadian pathways hold an intricate relationship with autophagy, the mechanistic target of rapamycin (mTOR), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), mammalian forkhead transcription factors (FoxOs), and the trophic factor erythropoietin. Autophagy induction is necessary to maintain circadian rhythm homeostasis and limit cortical neurodegenerative disease, but requires a fine balance in biological activity to foster proper circadian clock gene regulation that is intimately dependent upon mTOR, SIRT1, FoxOs, and growth factor expression. Circadian rhythm mechanisms offer innovative prospects for the development of new avenues to comprehend the underlying mechanisms of cognitive loss and forge ahead with new therapeutics for dementia that can offer effective clinical treatments.<\/jats:p>","DOI":"10.3390\/biom11071002","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T04:14:57Z","timestamp":1625804097000},"page":"1002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways"],"prefix":"10.3390","volume":"11","author":[{"given":"Kenneth","family":"Maiese","sequence":"first","affiliation":[{"name":"Cellular and Molecular Signaling, New York, NY 10022, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2011). Description of the global burden of NCDs, their risk factors and determinants. Global Status Report on Noncommunicable Diseases 2010, World Health Organization."},{"key":"ref_2","unstructured":"World Health Organization (2017). Global Action Plan on the Public Health Response to Dementia 2017\u20132025, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.irn.2020.01.009","article-title":"Dysregulation of metabolic flexibility: The impact of mTOR on autophagy in neurodegenerative disease","volume":"155","author":"Maiese","year":"2020","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/978-3-030-49844-3_11","article-title":"Alzheimer\u2019s Disease and Protein Kinases","volume":"1275","author":"Engin","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Maiese, K. (2021). Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders. Curr. Neurovasc. Res.","DOI":"10.2174\/18755739MTEzaMDMw2"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Odnokoz, O., Nakatsuka, K., Wright, C., Castellanos, J., Klichko, V.I., Kretzschmar, D., Orr, W.C., and Radyuk, S.N. (2021). Mitochondrial Redox Signaling Is Critical to the Normal Functioning of the Neuronal System. Front. Cell Dev. Biol.","DOI":"10.3389\/fcell.2021.613036"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rey, F., Ottolenghi, S., Giallongo, T., Balsari, A., Martinelli, C., Rey, R., Allevi, R., Giulio, A.M.D., Zuccotti, G.V., and Mazzucchelli, S. (2021). Mitochondrial Metabolism as Target of the Neuroprotective Role of Erythropoietin in Parkinson\u2019s Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10010121"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/17512433.2020.1698288","article-title":"Cognitive impairment with diabetes mellitus and metabolic disease: Innovative insights with the mechanistic target of rapamycin and circadian clock gene pathways","volume":"13","author":"Maiese","year":"2020","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_9","unstructured":"National Center for Health Statistics (2019). National Vital Statisitcs System."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"110841","DOI":"10.1016\/j.exger.2020.110841","article-title":"Kynurenine pathway, NAD(+) synthesis, and mitochondrial function: Targeting tryptophan metabolism to promote longevity and healthspan","volume":"132","author":"Sutphin","year":"2020","journal-title":"Exp. Gerontol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cheng, X., Song, C., Du, Y., Gaur, U., and Yang, M. (2020). Pharmacological Treatment of Alzheimer\u2019s Disease: Insights from Drosophila melanogaster. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134621"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.biopha.2018.12.052","article-title":"The roles of circular RNAs in human development and diseases","volume":"111","author":"Lee","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104481","DOI":"10.1016\/j.nbd.2019.104481","article-title":"Aging, lifestyle and dementia","volume":"130","author":"Wahl","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1042\/BST20170121","article-title":"The mechanistic target of rapamycin (mTOR) and the silent mating-type information regulation 2 homolog 1 (SIRT1): Oversight for neurodegenerative disorders","volume":"46","author":"Maiese","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Maiese, K. (2018). Sirtuins: Developing Innovative Treatments for Aged-Related Memory Loss and Alzheimer\u2019s Disease. Curr. Neurovasc. Res., 15.","DOI":"10.2174\/1567202616666181128120003"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.2741\/4886","article-title":"New Insights for nicotinamide: Metabolic disease, autophagy, and mTOR","volume":"25","author":"Maiese","year":"2020","journal-title":"Front. Biosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2174\/1567202611666140408104831","article-title":"Cutting through the Complexities of mTOR for the Treatment of Stroke","volume":"11","author":"Maiese","year":"2014","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.15761\/JTS.1000138","article-title":"The bright side of reactive oxygen species: Lifespan extension without cellular demise","volume":"2","author":"Maiese","year":"2016","journal-title":"J. Transl. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mladenovic Djordjevic, A., Loncarevic-Vasiljkovic, N., and Gonos, E.S. (2020). Dietary restriction and oxidative stress: Friends or enemies?. Antioxid. Redox Signal.","DOI":"10.1089\/ars.2019.7959"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101188","DOI":"10.1016\/j.arr.2020.101188","article-title":"Targeting metabolic pathways for extension of lifespan and healthspan across multiple species","volume":"64","author":"Parkhitko","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2174\/1567202614666171116102911","article-title":"Forkhead Transcription Factors: Formulating a FOXO Target for Cognitive Loss","volume":"14","author":"Maiese","year":"2017","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Maiese, K. (2021). Alcohol Use Disorder and Dementia: Critical Mechanisms for Cognitive Loss. Curr. Neurovasc. Res.","DOI":"10.2174\/1567202618666210212153458"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5815","DOI":"10.1007\/s12035-019-1475-8","article-title":"Mechanisms Associated with Type 2 Diabetes as a Risk Factor for Alzheimer-Related Pathology","volume":"56","author":"Su","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"587","DOI":"10.3109\/07853890.2014.941921","article-title":"Taking aim at Alzheimer\u2019s disease through the mammalian target of rapamycin","volume":"46","author":"Maiese","year":"2014","journal-title":"Ann. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.molmed.2012.11.001","article-title":"mTOR: On target for novel therapeutic strategies in the nervous system","volume":"19","author":"Maiese","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/s41598-018-37215-0","article-title":"Acute glucose fluctuation impacts microglial activity, leading to inflammatory activation or self-degradation","volume":"9","author":"Hsieh","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"111817","DOI":"10.1016\/j.fct.2020.111817","article-title":"Flavonoids targeting NRF2 in neurodegenerative disorders","volume":"146","author":"Khan","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kowalska, M., Piekut, T., Prendecki, M., Sodel, A., Kozubski, W., and Dorszewska, J. (2020). Mitochondrial and Nuclear DNA Oxidative Damage in Physiological and Pathological Aging. DNA Cell Biol., 39.","DOI":"10.1089\/dna.2019.5347"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s12017-019-08524-y","article-title":"The Promises and Challenges of Erythropoietin for Treatment of Alzheimer\u2019s Disease","volume":"21","author":"Sun","year":"2019","journal-title":"Neuromol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1567202616666190208094159","article-title":"MicroRNAs for the Treatment of Dementia and Alzheimer\u2019s Disease","volume":"16","author":"Maiese","year":"2019","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"773","DOI":"10.4103\/1673-5374.249224","article-title":"Impacting dementia and cognitive loss with innovative strategies: Mechanistic target of rapamycin, clock genes, circular non-coding ribonucleic acids, and Rho\/Rock","volume":"14","author":"Maiese","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/1570159X113116660047","article-title":"Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer\u2019s Disease","volume":"12","author":"Solhuber","year":"2014","journal-title":"Curr. Neuropharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2174\/1567202617666200721150331","article-title":"Addressing Alzheimer\u2019s Disease and Cognitive Loss through Autophagy","volume":"17","author":"Maiese","year":"2020","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_34","unstructured":"World Health Organization (2012). Dementia: A Public Health Priority, World Health Organization."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1038\/s41598-019-39828-5","article-title":"Cross-disease analysis of Alzheimer\u2019s disease and type-2 Diabetes highlights the role of autophagy in the pathophysiology of two highly comorbid diseases","volume":"9","author":"Caberlotto","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cacabelos, R., Carril, J.C., Cacabelos, N., Kazantsev, A.G., Vostrov, A.V., Corzo, L., Cacabelos, P., and Goldgaber, D. (2019). Sirtuins in Alzheimer\u2019s Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051249"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.mad.2018.11.002","article-title":"Circular RNA involvement in aging: An emerging player with great potential","volume":"178","author":"Cai","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chang, R., Maghribi, A.A., Vanderpoel, V., Vasilevko, V., Cribbs, D.H., Boado, R., Pardridge, W.M., and Sumbria, R.K. (2018). A Brain Penetrating Bifunctional Erythropoietin-Transferrin Receptor Antibody Fusion Protein for Alzheimer\u2019s Disease. Mol. Pharm.","DOI":"10.1021\/acs.molpharmaceut.8b00594"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e12801","DOI":"10.1111\/acel.12801","article-title":"The emerging roles of protein homeostasis-governing pathways in Alzheimer\u2019s disease","volume":"17","author":"Cheng","year":"2018","journal-title":"Aging Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5436","DOI":"10.1007\/s12035-018-1448-3","article-title":"The Role of Ceramide and Sphingosine-1-Phosphate in Alzheimer\u2019s Disease and Other Neurodegenerative Disorders","volume":"56","author":"Czubowicz","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"782","DOI":"10.3389\/fnins.2020.00782","article-title":"TRP Channels Role in Pain Associated With Neurodegenerative Diseases","volume":"14","author":"Duitama","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gonzalo-Gobernado, R., Perucho, J., Vallejo-Mu\u00f1oz, M., Casarejos, M.J., Reimers, D., Jim\u00e9nez-Escrig, A., G\u00f3mez, A., Ulzurrun de Asanza, G.M., and Baz\u00e1n, E. (2020). Liver Growth Factor \u201cLGF\u201d as a Therapeutic Agent for Alzheimer\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239201"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3389\/fnmol.2020.00058","article-title":"Lysophospholipids and Their G-Coupled Protein Signaling in Alzheimer\u2019s Disease: From Physiological Performance to Pathological Impairment","volume":"13","author":"Hao","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Huang, C., Wen, C., Yang, M., Li, A., Fan, C., Gan, D., Li, Q., Zhao, J., Zhu, L., and Lu, D. (2020). Astaxanthin Improved the Cognitive Deficits in APP\/PS1 Transgenic Mice Via Selective Activation of mTOR. J. Neuroimmune Pharmacol., 1.","DOI":"10.1007\/s11481-020-09953-4"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109126","DOI":"10.1016\/j.cbi.2020.109126","article-title":"Graphene oxide enhances \u03b2-amyloid clearance by inducing autophagy of microglia and neurons","volume":"325","author":"Li","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13830","DOI":"10.3390\/ijms131113830","article-title":"Oxidant Stress and Signal Transduction in the Nervous System with the PI 3-K, Akt, and mTOR Cascade","volume":"13","author":"Maiese","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5029","DOI":"10.1038\/s41598-020-61883-6","article-title":"Identification of Novel Alzheimer\u2019s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data","volume":"10","author":"Prokopenko","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1021\/acschemneuro.0c00067","article-title":"Resveratrol Differently Modulates Group I Metabotropic Glutamate Receptors Depending on Age in SAMP8 Mice","volume":"11","author":"Albasanz","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sedighi, M., Baluchnejadmojarad, T., Afshin-Majd, S., Amiri, M., Aminzade, M., and Roghani, M. (2020). Anti-aging Klotho Protects SH-SY5Y Cells Against Amyloid \u03b21-42 Neurotoxicity: Involvement of Wnt1\/pCREB\/Nrf2\/HO-1 Signaling. J. Mol. Neurosci.","DOI":"10.1007\/s12031-020-01621-9"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1007\/s10571-020-00801-w","article-title":"Neuroprotective Effects of Salidroside in a Mouse Model of Alzheimer\u2019s Disease","volume":"40","author":"Wang","year":"2020","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"20862","DOI":"10.18632\/aging.104104","article-title":"TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K\/AKT\/FoxO3a signaling pathway in Alzheimer\u2019s disease mice","volume":"12","author":"Wang","year":"2020","journal-title":"Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1038\/s41598-020-60682-3","article-title":"Shared Causal Paths underlying Alzheimer\u2019s dementia and Type 2 Diabetes","volume":"10","author":"Hu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"135322","DOI":"10.1016\/j.neulet.2020.135322","article-title":"FoxO1 overexpression reduces A\u03b2 production and tau phosphorylation in vitro","volume":"738","author":"Zhang","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"112063","DOI":"10.1016\/j.fct.2021.112063","article-title":"Signal transduction associated with lead-induced neurological disorders: A review","volume":"150","author":"Fang","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"569392","DOI":"10.1155\/2015\/569392","article-title":"FoxO Proteins in the Nervous System","volume":"2015","author":"Maiese","year":"2015","journal-title":"Anal. Cell Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4161\/oxim.2.5.9990","article-title":"New strategies for Alzheimer\u2019s disease and cognitive impairment","volume":"2","author":"Maiese","year":"2009","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_57","first-page":"2651","article-title":"Activation of EphA4 induced by EphrinA1 exacerbates disruption of the blood-brain barrier following cerebral ischemia-reperfusion via the Rho\/ROCK signaling pathway","volume":"16","author":"Chen","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"372","DOI":"10.4103\/1673-5374.179032","article-title":"Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR","volume":"11","author":"Maiese","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bahorik, A., Bobrow, K., Hoang, T., and Yaffe, K. (2021). Increased risk of dementia in older female US veterans with alcohol use disorder. Addiction.","DOI":"10.1111\/add.15416"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7389","DOI":"10.1007\/s12035-018-0908-0","article-title":"Qi Fu Yin-a Ming Dynasty Prescription for the Treatment of Dementia","volume":"55","author":"Ong","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.4103\/1673-5374.266070","article-title":"Jidong cognitive impairment cohort study: Objectives, design, and baseline screening","volume":"15","author":"Song","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1001\/archinternmed.2011.2230","article-title":"Role of intensive glucose control in development of renal end points in type 2 diabetes mellitus: Systematic review and meta-analysis intensive glucose control in type 2 diabetes","volume":"172","author":"Coca","year":"2012","journal-title":"Arch. Intern. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1007\/s40618-019-01052-3","article-title":"Sick fat: The good and the bad of old and new circulating markers of adipose tissue inflammation","volume":"42","author":"Barchetta","year":"2019","journal-title":"J. Endocrinol. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/abbs\/gmz156","article-title":"Glycogen synthase kinase-3 as a key regulator of cognitive function","volume":"52","author":"Fan","year":"2020","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5982","DOI":"10.1038\/s41467-020-19657-1","article-title":"Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells","volume":"11","author":"Esteban","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"21655","DOI":"10.1038\/s41598-020-78676-6","article-title":"FKBPL is associated with metabolic parameters and is a novel determinant of cardiovascular disease","volume":"10","author":"Januszewski","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4934206","DOI":"10.1155\/2020\/4934206","article-title":"Association of WISP1\/CCN4 with Risk of Overweight and Gestational Diabetes Mellitus in Chinese Pregnant Women","volume":"2020","author":"Liu","year":"2020","journal-title":"Dis. Markers"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"518","DOI":"10.4103\/1673-5374.155427","article-title":"Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease","volume":"10","author":"Maiese","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Maiese, K. (2015). New Insights for Oxidative Stress and Diabetes Mellitus. Oxidative Med. Cell. Longev., 2015.","DOI":"10.1155\/2015\/875961"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1038\/s41598-020-60213-0","article-title":"Metformin-induced suppression of IFN-alpha via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes","volume":"10","author":"Saenwongsa","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1093\/advances\/nmaa072","article-title":"Intake of \u03c9-6 Polyunsaturated Fatty Acid-Rich Vegetable Oils and Risk of Lifestyle Diseases","volume":"11","author":"Yamashima","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.jalz.2016.10.003","article-title":"Circadian alterations during early stages of Alzheimer\u2019s disease are associated with aberrant cycles of DNA methylation in BMAL1","volume":"13","author":"Cronin","year":"2017","journal-title":"Alzheimer\u2019s Dement. J. Alzheimer\u2019s Assoc."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)","volume":"17","author":"Klionsky","year":"2021","journal-title":"Autophagy"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Maiese, K. (2020). Nicotinamide: Oversight of Metabolic Dysfunction through SIRT1, mTOR, and Clock Genes. Curr. Neurovasc. Res., 17.","DOI":"10.2174\/15672026MTEx6NDImx"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5054","DOI":"10.3390\/molecules14125054","article-title":"Neuroprotection by radical avoidance: Search for suitable agents","volume":"14","author":"Hardeland","year":"2009","journal-title":"Molecules"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"170","DOI":"10.3389\/fnagi.2017.00170","article-title":"Neurodegeneration and the Circadian Clock","volume":"9","author":"Hood","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Vaccaro, A., Issa, A.R., Seugnet, L., Birman, S., and Klarsfeld, A. (2017). Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006507"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"101155","DOI":"10.1016\/j.arr.2020.101155","article-title":"Do not neglect the role of circadian rhythm in muscle atrophy","volume":"63","author":"Zhang","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/978-3-030-42667-5_9","article-title":"Resetting the Aging Clock: Implications for Managing Age-Related Diseases","volume":"1260","author":"Luz","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1097\/MNH.0000000000000611","article-title":"Circadian rhythms of mineral metabolism in chronic kidney disease-mineral bone disorder","volume":"29","author":"Egstrand","year":"2020","journal-title":"Curr. Opin. Nephrol. Hypertens"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Finger, A.M., and Kramer, A. (2020). Mammalian circadian systems: Organization and modern life challenges. Acta Physiol., e13548.","DOI":"10.1111\/apha.13548"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3892\/or.2020.7624","article-title":"PER2 inhibits proliferation and stemness of glioma stem cells via the Wnt\/\u03b2-catenin signaling pathway","volume":"44","author":"Ma","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"105595","DOI":"10.1016\/j.jsbmb.2020.105595","article-title":"Daily and seasonal mitochondrial protection: Unraveling common possible mechanisms involving vitamin D and melatonin","volume":"199","author":"Ferder","year":"2020","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Qi, X., Mitter, S.K., Yan, Y., Busik, J.V., Grant, M.B., and Boulton, M.E. (2020). Diurnal Rhythmicity of Autophagy Is Impaired in the Diabetic Retina. Cells, 9.","DOI":"10.3390\/cells9040905"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"657","DOI":"10.7150\/ijms.41515","article-title":"Exosomes from Human Periapical Cyst-MSCs: Theranostic Application in Parkinson\u2019s Disease","volume":"17","author":"Tatullo","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"299","DOI":"10.2174\/1567202614666170718092010","article-title":"Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer","volume":"14","author":"Maiese","year":"2017","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2174\/1567202615666180319151244","article-title":"Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors","volume":"15","author":"Maiese","year":"2018","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2008.06.050","article-title":"SIRT1 regulates circadian clock gene expression through PER2 deacetylation","volume":"134","author":"Asher","year":"2008","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"23318","DOI":"10.1074\/jbc.M116.737114","article-title":"Histone Deacetylase SIRT1 Controls Proliferation, Circadian Rhythm, and Lipid Metabolism during Liver Regeneration in Mice","volume":"291","author":"Bellet","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/cbf.2871","article-title":"Over-expression of circadian clock gene Bmal1 affects proliferation and the canonical Wnt pathway in NIH-3T3 cells","volume":"31","author":"Lin","year":"2013","journal-title":"Cell Biochem. Funct."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e12506","DOI":"10.1111\/jpi.12506","article-title":"Melatonin modulates dysregulated circadian clocks in mice with diethylnitrosamine-induced hepatocellular carcinoma","volume":"65","author":"Sanchez","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"R305","DOI":"10.1530\/ERC-19-0094","article-title":"Clock genes and cancer development in particular in endocrine tissues","volume":"26","author":"Angelousi","year":"2019","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_93","first-page":"2297","article-title":"The expression of the circadian gene TIMELESS in non-small-cell lung cancer and its clinical significance","volume":"13","author":"Zhang","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Bonmati-Carrion, M.A., and Tomas-Loba, A. (2021). Melatonin and Cancer: A Polyhedral Network Where the Source Matters. Antioxidants, 10.","DOI":"10.3390\/antiox10020210"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"16848","DOI":"10.3390\/ijms150916848","article-title":"Melatonin regulates aging and neurodegeneration through energy metabolism, epigenetics, autophagy and circadian rhythm pathways","volume":"15","author":"Jenwitheesuk","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"12455","DOI":"10.1111\/jpi.12455","article-title":"Melatonin alleviates adipose inflammation through elevating alpha-ketoglutarate and diverting adipose-derived exosomes to macrophages in mice","volume":"64","author":"Liu","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"E631","DOI":"10.1152\/ajpendo.00177.2019","article-title":"Disruptions to the Limb Muscle Core Molecular Clock Coincide with Changes in Mitochondrial Quality Control following Androgen Depletion","volume":"317","author":"Rossetti","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"13271","DOI":"10.1038\/s41598-020-70170-3","article-title":"Pharmacological activation of the circadian component REV-ERB inhibits HIV-1 replication","volume":"10","author":"Borrmann","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s41782-020-00111-7","article-title":"Elderly as a High-risk Group during COVID-19 Pandemic: Effect of Circadian Misalignment, Sleep Dysregulation and Melatonin Administration","volume":"4","author":"Cardinali","year":"2020","journal-title":"Sleep Vigil."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7625","DOI":"10.1111\/jcmm.15398","article-title":"Melatonin modulates mitophagy, innate immunity and circadian clocks in a model of viral-induced fulminant hepatic failure","volume":"24","author":"Crespo","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"110147","DOI":"10.1016\/j.mehy.2020.110147","article-title":"Are night shift workers at an increased risk for COVID-19?","volume":"144","author":"Lim","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Maiese, K. (2020). Circadian Clock Genes: Targeting Innate Immunity for Antiviral Strategies Against COVID-19. Curr. Neurovasc. Res.","DOI":"10.2174\/15672026MTEyjMDEf5"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Mazzoccoli, G., Vinciguerra, M., Carbone, A., and Rel\u00f3gio, A. (2020). The Circadian Clock, the Immune System, and Viral Infections: The Intricate Relationship Between Biological Time and Host-Virus Interaction. Pathogens, 9.","DOI":"10.3390\/pathogens9020083"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"654","DOI":"10.17269\/s41997-020-00382-7","article-title":"Sleep and circadian rhythm in response to the COVID-19 pandemic","volume":"111","author":"Morin","year":"2020","journal-title":"Can. J. Public Health"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4845","DOI":"10.1111\/bph.15140","article-title":"The case for chronotherapy in COVID-19-induced acute respiratory distress syndrome","volume":"177","author":"Tamimi","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_106","first-page":"332","article-title":"The Mechanistic Target of Rapamycin (mTOR): Novel Considerations as an Antiviral Treatment","volume":"17","author":"Maiese","year":"2020","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"12377","DOI":"10.1111\/jpi.12377","article-title":"Melatonin and the pathologies of weakened or dysregulated circadian oscillators","volume":"62","author":"Hardeland","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Jenwitheesuk, A., Park, S., Wongchitrat, P., Tocharus, J., Mukda, S., Shimokawa, I., and Govitrapong, P. (2017). Comparing the Effects of Melatonin with Caloric Restriction in the Hippocampus of Aging Mice: Involvement of Sirtuin1 and the FOXOs Pathway. Neurochem. Res.","DOI":"10.1007\/s11064-017-2369-7"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/mp.2014.138","article-title":"Circadian dysregulation of clock genes: Clues to rapid treatments in major depressive disorder","volume":"20","author":"Bunney","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.4103\/0366-6999.204920","article-title":"Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson\u2019s Disease","volume":"130","author":"Li","year":"2017","journal-title":"Chin. Med. J."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Yu, M., Zhang, H., Wang, B., Zhang, Y., Zheng, X., Shao, B., Zhuge, Q., and Jin, K. (2021). Key Signaling Pathways in Aging and Potential Interventions for Healthy Aging. Cells, 10.","DOI":"10.3390\/cells10030660"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3389\/fphar.2017.00315","article-title":"Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight","volume":"8","author":"Wu","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"615","DOI":"10.3233\/JAD-160942","article-title":"Alterations of Clock Gene RNA Expression in Brain Regions of a Triple Transgenic Model of Alzheimer\u2019s Disease","volume":"59","author":"Bellanti","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"S182","DOI":"10.4103\/0028-3886.259124","article-title":"Current trends and future perspectives of space neuroscience towards preparation for interplanetary missions","volume":"67","author":"Frantzidis","year":"2019","journal-title":"Neurol. India"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1177\/1073858417691030","article-title":"The Glymphatic Pathway: Waste Removal from the CNS via Cerebrospinal Fluid Transport","volume":"23","author":"Benveniste","year":"2017","journal-title":"Neuroscientist"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Liu, Y., Niu, L., Liu, X., Cheng, C., and Le, W. (2021). Recent Progress in Non-motor Features of Parkinson\u2019s Disease with a Focus on Circadian Rhythm Dysregulation. Neurosci. Bull.","DOI":"10.1007\/s12264-021-00711-x"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Elnour, M.A.A., Saleh, A.A., Kalantan, M.M., and Mirghani, H.O. (2019). The relationship between coffee intake, obstructive sleep apnea risk, and type 2 diabetes glycemic control, in Tabuk City, The Kingdom of Saudi Arabia: A case-control study. BMC Res. Notes, 12.","DOI":"10.1186\/s13104-019-4838-3"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"7489795","DOI":"10.1155\/2020\/7489795","article-title":"Association of Glycemic Indices (Hyperglycemia, Glucose Variability, and Hypoglycemia) with Oxidative Stress and Diabetic Complications","volume":"2020","author":"Papachristoforou","year":"2020","journal-title":"J. Diabetes Res."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Wang, X., Xu, Z., Cai, Y., Zeng, S., Peng, B., Ren, X., Yan, Y., and Gong, Z. (2020). Rheostatic Balance of Circadian Rhythm and Autophagy in Metabolism and Disease. Front. Cell Dev. Biol., 24.","DOI":"10.3389\/fcell.2020.616434"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1517\/17460441.2013.736485","article-title":"Novel directions for diabetes mellitus drug discovery","volume":"8","author":"Maiese","year":"2013","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.lfs.2019.01.006","article-title":"Roles of sleep deprivation in cardiovascular dysfunctions","volume":"219","author":"Liu","year":"2019","journal-title":"Life Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3109\/07420528.2015.1137581","article-title":"Circadian rhythm of autophagy proteins in hippocampus is blunted by sleep fragmentation","volume":"33","author":"He","year":"2016","journal-title":"Chronobiol. Int."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2174\/1567202614666170619083239","article-title":"The hippocampal autophagic machinery is depressed in the absence of the circadian clock protein PER1 that may lead to vulnerability during cerebral ischemia","volume":"14","author":"Rami","year":"2017","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"104538","DOI":"10.1016\/j.phrs.2019.104538","article-title":"Caffeic acid reduces A53T alpha-synuclein by activating JNK\/Bcl-2-mediated autophagy in vitro and improves behaviour and protects dopaminergic neurons in a mouse model of Parkinson\u2019s disease","volume":"150","author":"Zhang","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1097\/WNR.0000000000001202","article-title":"Glaucocalyxin A as a natural product increases amyloid beta clearance and decreases tau phosphorylation involving the mammalian target of rapamycin signaling pathway","volume":"30","author":"Zhou","year":"2019","journal-title":"Neuroreport"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13041-014-0056-z","article-title":"Impairment of autophagy in the central nervous system during lipopolysaccharide-induced inflammatory stress in mice","volume":"7","author":"Francois","year":"2014","journal-title":"Mol. Brain"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40478-016-0324-5","article-title":"The ALS\/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway","volume":"4","author":"Sullivan","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.neuron.2014.12.019","article-title":"Reinstating aberrant mTORC1 activity in Huntington\u2019s disease mice improves disease phenotypes","volume":"85","author":"Lee","year":"2015","journal-title":"Neuron"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1111\/bcp.12804","article-title":"Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders","volume":"82","author":"Maiese","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4782820","DOI":"10.1155\/2017\/4782820","article-title":"The Effect of Pyrroloquinoline Quinone on the Expression of WISP1 in Traumatic Brain Injury","volume":"2017","author":"Ye","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"724","DOI":"10.2174\/1871527316666170124164306","article-title":"The effect of pyrroloquinoline quinone on apoptosis and autophagy in traumatic brain injury","volume":"16","author":"Zhang","year":"2017","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e15002","DOI":"10.1111\/jnc.15002","article-title":"Autophagy in neurodegeneration: New insights underpinning therapy for neurological diseases","volume":"154","author":"Corti","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3389\/fnmol.2019.00299","article-title":"Targeting Alpha-Synuclein as a Therapy for Parkinson\u2019s Disease","volume":"12","author":"Fields","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40035-019-0145-0","article-title":"Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson\u2019s disease","volume":"8","author":"Zhou","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Jayaraj, R.L., Beiram, R., Azimullah, S., Mf, N.M., Ojha, S.K., Adem, A., and Jalal, F.Y. (2020). Valeric Acid Protects Dopaminergic Neurons by Suppressing Oxidative Stress, Neuroinflammation and Modulating Autophagy Pathways. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207670"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1517\/14728222.2012.719499","article-title":"Targeting disease through novel pathways of apoptosis and autophagy","volume":"16","author":"Maiese","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"102112","DOI":"10.1016\/j.npep.2020.102112","article-title":"Regulatory effects of ghrelin on endoplasmic reticulum stress, oxidative stress, and autophagy: Therapeutic potential","volume":"85","author":"Wang","year":"2021","journal-title":"Neuropeptides"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s43032-020-00277-5","article-title":"The Emerging Key Role of Klotho in the Hypothalamus-Pituitary-Ovarian Axis","volume":"28","author":"Xie","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Zhou, Q., Tang, S., Zhang, X., and Chen, L. (2021). Targeting PRAS40: A novel therapeutic strategy for human diseases. J. Drug Target., 1\u201344.","DOI":"10.1080\/1061186X.2021.1882470"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.freeradbiomed.2021.04.025","article-title":"mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in the progression of this dementing disorder","volume":"169","author":"Perluigi","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12539-019-00347-6","article-title":"A Systems Biology Roadmap to Decode mTOR Control System in Cancer","volume":"12","author":"Dorvash","year":"2020","journal-title":"Interdiscip Sci."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Preau, S., Ambler, M., Sigurta, A., Kleyman, A., Dyson, A., Hill, N.E., Boulanger, E., and Singer, M. (2019). Protein recycling and limb muscle recovery after critical illness in slow- and fast-twitch limb muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol.","DOI":"10.1152\/ajpregu.00221.2018"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s40520-015-0398-0","article-title":"Influence of age-related learning and memory capacity of mice: Different effects of a high and low caloric diet","volume":"28","author":"Dong","year":"2016","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"241","DOI":"10.15761\/JTS.1000146","article-title":"Forkhead transcription factors: New considerations for alzheimer\u2019s disease and dementia","volume":"2","author":"Maiese","year":"2016","journal-title":"J. Transl. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"5555","DOI":"10.1038\/srep05555","article-title":"Protective effect of Dl-3n-butylphthalide on learning and memory impairment induced by chronic intermittent hypoxia-hypercapnia exposure","volume":"4","author":"Min","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1523\/JNEUROSCI.3229-16.2017","article-title":"Selenomethionine mitigates cognitive decline by targeting both tau hyperphosphorylation and autophagic clearance in an Alzheimer\u2019s disease mouse model","volume":"37","author":"Zhang","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1007\/s00436-021-07070-6","article-title":"The host mTOR pathway and parasitic diseases pathogenesis","volume":"120","author":"Rashidi","year":"2021","journal-title":"Parasitol. Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2017.12.026","article-title":"Accumulation of beta-synuclein in cortical neurons is associated with autophagy attenuation in the brains of dementia with Lewy body patients","volume":"1681","author":"Evans","year":"2018","journal-title":"Brain Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"12115","DOI":"10.1038\/srep12115","article-title":"Fasting activates macroautophagy in neurons of Alzheimer\u2019s disease mouse model but is insufficient to degrade amyloid-beta","volume":"5","author":"Chen","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1007\/s12035-017-0524-4","article-title":"Time-of-Day Dependent Neuronal Injury after Ischemic Stroke: Implication of Circadian Clock Transcriptional Factor Bmal1 and Survival Kinase AKT","volume":"55","author":"Beker","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3892\/ol.2016.5430","article-title":"Per2 participates in AKT-mediated drug resistance in A549\/DDP lung adenocarcinoma cells","volume":"13","author":"Chen","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Ramanathan, C., Kathale, N.D., Liu, D., Lee, C., Freeman, D.A., Hogenesch, J.B., Cao, R., and Liu, A.C. (2018). mTOR signaling regulates central and peripheral circadian clock function. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007369"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jneuroim.2016.09.008","article-title":"Everolimus (RAD001) ameliorates vascular cognitive impairment by regulating microglial function via the mTORC1 signaling pathway","volume":"299","author":"Chen","year":"2016","journal-title":"J. Neuroimmunol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11357-019-00113-y","article-title":"Topical rapamycin reduces markers of senescence and aging in human skin: An exploratory, prospective, randomized trial","volume":"41","author":"Chung","year":"2019","journal-title":"Geroscience"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4142\/jvs.2017.18.1.11","article-title":"Temporal changes in mammalian target of rapamycin (mTOR) and phosphorylated-mTOR expressions in the hippocampal CA1 region of rat with vascular dementia","volume":"18","author":"Park","year":"2017","journal-title":"J. Vet. Sci."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"6619515","DOI":"10.1155\/2021\/6619515","article-title":"Role of BDNF-mTORC1 Signaling Pathway in Female Depression","volume":"2021","author":"An","year":"2021","journal-title":"Neural Plast."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1111\/bph.15351","article-title":"Phytocannabinoid-dependent mTORC1 regulation is dependent upon inositol polyphosphate multikinase activity","volume":"178","author":"Warren","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"506","DOI":"10.5483\/BMBRep.2011.44.8.506","article-title":"The functions of mTOR in ischemic diseases","volume":"44","author":"Hwang","year":"2011","journal-title":"BMB Rep."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"329","DOI":"10.2174\/1567202613666160729164900","article-title":"Erythropoietin and mTOR: A \u201cOne-Two Punch\u201d for Aging-Related Disorders Accompanied by Enhanced Life Expectancy","volume":"13","author":"Maiese","year":"2016","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/1566524013666131118103706","article-title":"Hypothalamic mTOR: The rookie energy sensor","volume":"14","author":"Roa","year":"2014","journal-title":"Curr. Mol. Med."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Maiese, K. (2021). Sirtuins in Metabolic Disease: Innovative Therapeutic Strategies with SIRT1, AMPK, mTOR, and Nicotinamide. Sirtuin Biology in Cancer and Metabolic Disease: Cellular Pathways for Clinical Discovery, Elsevier.","DOI":"10.1016\/B978-0-12-822467-0.00006-1"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"448","DOI":"10.4103\/1673-5374.291382","article-title":"Targeting the core of neurodegeneration: FoxO, mTOR, and SIRT1","volume":"16","author":"Maiese","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Xu, T., Liu, J., Li, X.R., Yu, Y., Luo, X., Zheng, X., Cheng, Y., Yu, P.Q., and Liu, Y. (2021). The mTOR\/NF-\u03baB Pathway Mediates Neuroinflammation and Synaptic Plasticity in Diabetic Encephalopathy. Mol. Neurobiol.","DOI":"10.1007\/s12035-021-02390-1"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1099\/jgv.0.001356","article-title":"mTORC1 restricts hepatitis C virus RNA replication through ULK1-mediated suppression of miR-122 and facilitates post-replication events","volume":"101","author":"Johri","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.4103\/1673-5374.139453","article-title":"Driving neural regeneration through the mammalian target of rapamycin","volume":"9","author":"Maiese","year":"2014","journal-title":"Neural Regen. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.bbrc.2015.05.041","article-title":"Proline-rich AKT substrate of 40-kDa (PRAS40) in the pathophysiology of cancer","volume":"463","author":"Malla","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e929279","DOI":"10.12659\/AOT.929279","article-title":"Effect of Calcineurin Inhibitors and Mammalian Target of Rapamycin Inhibitors on the Course of COVID-19 in Kidney Transplant Recipients","volume":"26","author":"Hasbal","year":"2021","journal-title":"Ann. Transplant."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Patocka, J., Kuca, K., Oleksak, P., Nepovimova, E., Valis, M., Novotny, M., and Klimova, B. (2021). Rapamycin: Drug Repurposing in SARS-CoV-2 Infection. Pharmaceuticals, 14.","DOI":"10.3390\/ph14030217"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Pereira, G., Le\u00e3o, A., Erustes, A.G., Morais, I.B.M., Vrechi, T.A.M., Zamarioli, L.D.S., Pereira, C.A.S., Marchioro, L.O., Sperandio, L.P., and Lins, \u00cd.V.F. (2021). Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084067"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Shi, G., Chiramel, A.I., Majdoul, S., Lai, K.K., Das, S., Beare, P.A., Andresson, T., Best, S.M., and Compton, A.A. (2021). Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2. bioRxiv.","DOI":"10.1101\/2021.04.15.440067"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13024-021-00428-5","article-title":"Mammalian\/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration","volume":"16","author":"Querfurth","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.pneurobio.2012.08.001","article-title":"Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin","volume":"99","author":"Chong","year":"2012","journal-title":"Prog. Neurobiol."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Huang, D., Shen, S., Cai, M., Jin, L., Lu, J., Xu, K., Zhang, J., Feng, G., Hu, Y., and Zheng, K. (2019). Role of mTOR complex in IGF-1 induced neural differentiation of DPSCs. J. Mol. Histol.","DOI":"10.1007\/s10735-019-09825-z"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/ncb1183","article-title":"Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive","volume":"6","author":"Jacinto","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3389\/fnagi.2019.00314","article-title":"Melatonin and Rapamycin Attenuate Isoflurane-Induced Cognitive Impairment through Inhibition of Neuroinflammation by Suppressing the mTOR Signaling in the Hippocampus of Aged Mice","volume":"11","author":"Yuan","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/152308603322110832","article-title":"Metallothionein attenuates 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in dopaminergic neurons","volume":"5","author":"Sharma","year":"2003","journal-title":"Antioxid. Redox Signal."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.exger.2012.11.012","article-title":"Improvement of oxidative stress and immunity by melatonin: An age dependent study in golden hamster","volume":"48","author":"Vishwas","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cca.2020.04.016","article-title":"Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function","volume":"508","author":"Zhang","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.cell.2017.07.042","article-title":"Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging","volume":"170","author":"Sato","year":"2017","journal-title":"Cell"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2017.01.022","article-title":"Caveolin1\/protein arginine methyltransferase1\/sirtuin1 axis as a potential target against endothelial dysfunction","volume":"119","author":"Charles","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1517\/14728222.2012.648926","article-title":"SIRT1: New avenues of discovery for disorders of oxidative stress","volume":"16","author":"Chong","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.toxlet.2017.04.018","article-title":"Erythropoietin activates SIRT1 to protect human cardiomyocytes against doxorubicin-induced mitochondrial dysfunction and toxicity","volume":"275","author":"Cui","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1007\/s11427-016-9027-6","article-title":"Retinoic acid ameliorates high-fat diet-induced liver steatosis through sirt1","volume":"60","author":"Geng","year":"2017","journal-title":"Sci. China Life Sci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"235","DOI":"10.4252\/wjsc.v7.i2.235","article-title":"SIRT1 and stem cells: In the forefront with cardiovascular disease, neurodegeneration and cancer","volume":"7","author":"Maiese","year":"2015","journal-title":"World J. Stem Cells"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"82","DOI":"10.2174\/1567202613666161129112822","article-title":"Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease","volume":"14","author":"Maiese","year":"2017","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"10216","DOI":"10.1038\/s41598-018-26905-4","article-title":"Sir-2.1 mediated attenuation of alpha-synuclein expression by Alaskan bog blueberry polyphenols in a transgenic model of Caenorhabditis elegans","volume":"8","author":"Maulik","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"104384","DOI":"10.1016\/j.bioorg.2020.104384","article-title":"Synthesis and neuroprotective effects of novel chalcone-triazole hybrids","volume":"105","author":"Sooknual","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2174\/1567202617666200327125257","article-title":"Prospects and Perspectives for WISP1 (CCN4) in Diabetes Mellitus","volume":"17","author":"Maiese","year":"2020","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.18632\/aging.101966","article-title":"Exploration of age-related mitochondrial dysfunction and the anti-aging effects of resveratrol in zebrafish retina","volume":"11","author":"Wang","year":"2019","journal-title":"Aging"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"599389","DOI":"10.3389\/fcell.2020.599389","article-title":"A Novel PDE4D Inhibitor BPN14770 Reverses Scopolamine-Induced Cognitive Deficits via cAMP\/SIRT1\/Akt\/Bcl-2 Pathway","volume":"8","author":"Wang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_191","first-page":"1","article-title":"Protective role of mitoquinone against impaired mitochondrial homeostasis in metabolic syndrome","volume":"20","author":"Yang","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11010-018-3476-8","article-title":"Genistein protects against ox-LDL-induced senescence through enhancing SIRT1\/LKB1\/AMPK-mediated autophagy flux in HUVECs","volume":"455","author":"Zhang","year":"2019","journal-title":"Mol. Cell Biochem."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.molmed.2008.03.002","article-title":"OutFOXOing disease and disability: The therapeutic potential of targeting FoxO proteins","volume":"14","author":"Maiese","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1080\/13880209.2021.1877734","article-title":"Kaempferol suppresses acetaminophen-induced liver damage by upregulation\/activation of SIRT1","volume":"59","author":"BinMowyna","year":"2021","journal-title":"Pharm. Biol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"8891544","DOI":"10.1155\/2021\/8891544","article-title":"Resveratrol Suppresses Severe Acute Pancreatitis-Induced Microcirculation Disturbance through Targeting SIRT1-FOXO1 Axis","volume":"2021","author":"Rong","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Shati, A.A., and El-Kott, A.F. (2021). Acylated ghrelin protects against Doxorubicin-induced nephropathy by activating SIRT1. Basic Clin. Pharmacol. Toxicol.","DOI":"10.1111\/bcpt.13569"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Yaman, D., Takmaz, T., Y\u00fcksel, N., Din\u00e7er, S.A., and \u015eahin, F. (2020). Evaluation of silent information regulator T (SIRT) 1 and Forkhead Box O (FOXO) transcription factor 1 and 3a genes in glaucoma. Mol. Biol. Rep.","DOI":"10.1007\/s11033-020-05994-3"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1042\/CS20080113","article-title":"FoxO proteins: Cunning concepts and considerations for the cardiovascular system","volume":"116","author":"Maiese","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"e14969","DOI":"10.1111\/jnc.14969","article-title":"FoxO3a requires BAF57, a subunit of chromatin remodeler SWI\/SNF complex for induction of PUMA in a model of Parkinson\u2019s disease","volume":"154","author":"Sanphui","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"7917","DOI":"10.1523\/JNEUROSCI.0363-14.2014","article-title":"TGFbeta signaling regulates the timing of CNS myelination by modulating oligodendrocyte progenitor cell cycle exit through SMAD3\/4\/FoxO1\/Sp1","volume":"34","author":"Palazuelos","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/1567202618666210212153458","article-title":"Novel Insights for Multiple Sclerosis and Demyelinating Disorders with Apoptosis, Autophagy, FoxO, and mTOR","volume":"18","author":"Maiese","year":"2021","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"144172","DOI":"10.1016\/j.gene.2019.144172","article-title":"The effect of FOXO gene family variants and global DNA metylation on RRMS disease","volume":"726","author":"Emre","year":"2020","journal-title":"Gene"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1074\/jbc.M116.744730","article-title":"Tribbles Pseudokinase 3 Induces Both Apoptosis and Autophagy in Amyloid-beta-induced Neuronal Death","volume":"292","author":"Saleem","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2741\/4889","article-title":"Signaling pathways and effectors of aging","volume":"26","author":"Tabibzadeh","year":"2021","journal-title":"Front. Biosci."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"135882","DOI":"10.1016\/j.neulet.2021.135882","article-title":"Expression of FOXO transcription factors in the brain following traumatic brain injury","volume":"753","author":"Liu","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Maiese, K. (2021). Novel Treatment Strategies for Neurodegenerative Disease with Sirtuins. Sirtuin Biology in Medicine: Targeting New Avenues of Care in Development, Aging, and Disease, Elsevier.","DOI":"10.1016\/B978-0-12-814118-2.00001-X"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"5289","DOI":"10.1074\/jbc.M110.163667","article-title":"FoxO1 Mediates an Autofeedback Loop Regulating SIRT1 Expression","volume":"286","author":"Xiong","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cbi.2015.07.013","article-title":"Hydrogen-rich water attenuates amyloid beta-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells","volume":"240","author":"Lin","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.3892\/mmr.2016.4957","article-title":"Effect and mechanism of fuzhisan and donepezil on the sirtuin 1 pathway and amyloid precursor protein metabolism in PC12 cells","volume":"13","author":"Guo","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.celrep.2019.12.090","article-title":"Cross-talk between CD38 and TTP Is Essential for Resolution of Inflammation during Microbial Sepsis","volume":"30","author":"Joe","year":"2020","journal-title":"Cell Rep."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12964-019-0498-0","article-title":"mTOR may interact with PARP-1 to regulate visible light-induced parthanatos in photoreceptors","volume":"18","author":"Pan","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1172\/JCI46243","article-title":"Hepatic Sirt1 deficiency in mice impairs mTorc2\/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance","volume":"121","author":"Wang","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Yin, Q., Wang, J.F., Xu, X.H., and Xie, H. (2020). Effect of lycopene on pain facilitation and the SIRT1\/mTOR pathway in the dorsal horn of burn injury rats. Eur. J. Pharmacol., 173365.","DOI":"10.1016\/j.ejphar.2020.173365"},{"key":"ref_214","first-page":"55","article-title":"MicroRNAs and SIRT1: A Strategy for Stem Cell Renewal and Clinical Development?","volume":"1","author":"Maiese","year":"2015","journal-title":"J. Transl. Sci."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1007\/s10495-019-01559-3","article-title":"Inhibition of SIRT1\/2 upregulates HSPA5 acetylation and induces pro-survival autophagy via ATF4-DDIT4-mTORC1 axis in human lung cancer cells","volume":"24","author":"Mu","year":"2019","journal-title":"Apoptosis"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.nutres.2017.03.005","article-title":"Nicotinamide protects hepatocytes against palmitate-induced lipotoxicity via SIRT1-dependent autophagy induction","volume":"40","author":"Shen","year":"2017","journal-title":"Nutr. Res."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1002\/jnr.22725","article-title":"Sirt1 overexpression in neurons promotes neurite outgrowth and cell survival through inhibition of the mTOR signaling","volume":"89","author":"Guo","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1002\/stem.1641","article-title":"SIRT1 positively regulates autophagy and mitochondria function in embryonic stem cells under oxidative stress","volume":"32","author":"Ou","year":"2014","journal-title":"Stem Cells"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1530\/JME-19-0080","article-title":"Aldose reductase regulates hyperglycemia-induced HUVEC death via SIRT1\/AMPK-alpha1\/mTOR pathway","volume":"63","author":"Pal","year":"2019","journal-title":"J. Mol. Endocrinol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"41082","DOI":"10.1038\/srep41082","article-title":"Hormetic effect of panaxatriol saponins confers neuroprotection in PC12 cells and zebrafish through PI3K\/AKT\/mTOR and AMPK\/SIRT1\/FOXO3 pathways","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1111\/j.1463-1326.2011.01466.x","article-title":"Metformin opposes impaired AMPK and SIRT1 function and deleterious changes in core clock protein expression in white adipose tissue of genetically-obese db\/db mice","volume":"13","author":"Caton","year":"2011","journal-title":"Diabetes Obes. Metab."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.dnarep.2014.04.005","article-title":"The evolving role of the NAD+\/nicotinamide metabolome in skin homeostasis, cellular bioenergetics, and aging","volume":"23","author":"Oblong","year":"2014","journal-title":"DNA Repair"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s00223-020-00741-z","article-title":"Melatonin Rescues the Ti Particle-Impaired Osteogenic Potential of Bone Marrow Mesenchymal Stem Cells via the SIRT1\/SOD2 Signaling Pathway","volume":"107","author":"Zhang","year":"2020","journal-title":"Calcif. Tissue Int."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1126\/science.1170803","article-title":"Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1","volume":"324","author":"Nakahata","year":"2009","journal-title":"Science"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"220","DOI":"10.2174\/156720211796558069","article-title":"Erythropoietin Employs Cell Longevity Pathways of SIRT1 to Foster Endothelial Vascular Integrity During Oxidant Stress","volume":"8","author":"Hou","year":"2011","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.2337\/db13-0518","article-title":"PPARalpha and Sirt1 mediate erythropoietin action in increasing metabolic activity and browning of white adipocytes to protect against obesity and metabolic disorders","volume":"62","author":"Wang","year":"2013","journal-title":"Diabetes"},{"key":"ref_227","first-page":"6870","article-title":"rhEPO affects apoptosis in hippocampus of aging rats by upregulating SIRT1","volume":"8","author":"Wu","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1001\/jama.293.1.90","article-title":"New avenues of exploration for erythropoietin","volume":"293","author":"Maiese","year":"2005","journal-title":"JAMA"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2741\/4408","article-title":"Regeneration in the nervous system with erythropoietin","volume":"21","author":"Maiese","year":"2016","journal-title":"Front. Biosci."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.4239\/wjd.v6.i14.1259","article-title":"Erythropoietin and diabetes mellitus","volume":"6","author":"Maiese","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cytogfr.2008.01.004","article-title":"Raves and risks for erythropoietin","volume":"19","author":"Maiese","year":"2008","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_232","doi-asserted-by":"crossref","unstructured":"Ezenwa, B., Ezeaka, C., Fajolu, I., Ogbenna, A., Olowoyeye, O., Nwaiwu, O., Opoola, Z., and Olorunfemi, G. (2020). Impact of Erythropoietin in the management of Hypoxic Ischaemic Encephalopathy in resource-constrained settings: Protocol for a randomized control trial. BMC Neurol., 20.","DOI":"10.1186\/s12883-020-01751-y"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"106330","DOI":"10.1016\/j.intimp.2020.106330","article-title":"An effective erythropoietin dose regimen protects against severe nerve injury-induced pathophysiological changes with improved neural gene expression and enhances functional recovery","volume":"82","author":"Govindappa","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Jarero-Basulto, J., Rivera-Cervantes, M., Gasca-Mart\u00ednez, D., Garc\u00eda-Sierra, F., Gasca-Mart\u00ednez, Y., and Beas-Z\u00e1rate, C. (2020). Current Evidence on the Protective Effects of Recombinant Human Erythropoietin and Its Molecular Variants against Pathological Hallmarks of Alzheimer\u2019s Disease. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120424"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41398-018-0270-z","article-title":"GSK3beta: A plausible mechanism of cognitive and hippocampal changes induced by erythropoietin treatment in mood disorders?","volume":"8","author":"Inkster","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-3-030-35582-1_2","article-title":"Erythropoietin Signaling in the Microenvironment of Tumors and Healthy Tissues","volume":"1223","author":"Liu","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_237","doi-asserted-by":"crossref","unstructured":"Negri, S., Faris, P., Rosti, V., Antognazza, M.R., Lodola, F., and Moccia, F. (2020). Endothelial TRPV1 as an Emerging Molecular Target to Promote Therapeutic Angiogenesis. Cells, 9.","DOI":"10.3390\/cells9061341"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s11060-020-03602-9","article-title":"AKT\/GSK-3\u03b2\/\u03b2-catenin signaling pathway participates in erythropoietin-promoted glioma proliferation","volume":"149","author":"Tang","year":"2020","journal-title":"J. Neurooncol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.preteyeres.2011.11.003","article-title":"From oxygen to erythropoietin: Relevance of hypoxia for retinal development, health and disease","volume":"31","author":"Caprara","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.biopha.2008.01.009","article-title":"Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus","volume":"62","author":"Maiese","year":"2008","journal-title":"Biomed. Pharmacother."},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Entezari, M., Flavarjani, Z.K., Ramezani, A., Nikkhah, H., Karimi, S., Moghadam, H.F., Daftarian, N., and Yaseri, M. (2019). Combination of intravitreal bevacizumab and erythropoietin versus intravitreal bevacizumab alone for refractory diabetic macular edema: A randomized double-blind clinical trial. Graefes Arch. Clin. Exp. Ophthalmol.","DOI":"10.1007\/s00417-019-04383-2"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"10395","DOI":"10.1038\/s41598-019-46894-2","article-title":"Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes","volume":"9","author":"Montesano","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1161\/01.CIR.0000039103.58920.1F","article-title":"Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases","volume":"106","author":"Chong","year":"2002","journal-title":"Circulation"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/sj.bjp.0705161","article-title":"Erythropoietin fosters both intrinsic and extrinsic neuronal protection through modulation of microglia, Akt1, Bad, and caspase-mediated pathways","volume":"138","author":"Chong","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"187","DOI":"10.18632\/aging.100440","article-title":"Prevention of beta-amyloid degeneration of microglia by erythropoietin depends on Wnt1, the PI 3-K\/mTOR pathway, Bad, and Bcl-xL","volume":"4","author":"Shang","year":"2012","journal-title":"Aging"},{"key":"ref_246","doi-asserted-by":"crossref","unstructured":"Chong, Z.Z., Shang, Y.C., Wang, S., and Maiese, K. (2012). PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045456"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/jnr.10528","article-title":"Erythropoietin prevents early and late neuronal demise through modulation of Akt1 and induction of caspase 1, 3, and 8","volume":"71","author":"Chong","year":"2003","journal-title":"J. Neurosci. Res."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1179\/1743132813Y.0000000284","article-title":"Erythropoietin exerts cell protective effect by activating PI3K\/Akt and MAPK pathways in C6 Cells","volume":"36","author":"Kwon","year":"2014","journal-title":"Neurol. Res."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s11010-013-1821-5","article-title":"The AKT\/mTOR pathway mediates neuronal protective effects of erythropoietin in sepsis","volume":"385","author":"Wang","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1007\/s12035-015-9316-x","article-title":"The Neuroprotective Effect of Erythropoietin on Rotenone-Induced Neurotoxicity in SH-SY5Y Cells Through the Induction of Autophagy","volume":"53","author":"Jang","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"184","DOI":"10.2174\/1567202614666170313105337","article-title":"Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin","volume":"14","author":"Maiese","year":"2017","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_252","doi-asserted-by":"crossref","unstructured":"Yu, Y., Shiou, S.R., Guo, Y., Lu, L., Westerhoff, M., Sun, J., Petrof, E.O., and Claud, E.C. (2013). Erythropoietin protects epithelial cells from excessive autophagy and apoptosis in experimental neonatal necrotizing enterocolitis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069620"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"270","DOI":"10.2174\/156720211798120990","article-title":"Erythropoietin and Wnt1 Govern Pathways of mTOR, Apaf-1, and XIAP in Inflammatory Microglia","volume":"8","author":"Shang","year":"2011","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/156720212803530618","article-title":"WNT1 Inducible Signaling Pathway Protein 1 (WISP1) Targets PRAS40 to Govern beta-Amyloid Apoptotic Injury of Microglia","volume":"9","author":"Shang","year":"2012","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s13577-019-00248-2","article-title":"Pathophysiological significance of clock genes BMAL1 and PER2 as erythropoietin-controlling factors in acute blood hemorrhage","volume":"32","author":"Tani","year":"2019","journal-title":"Hum. Cell"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/1002\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:28:08Z","timestamp":1760164088000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/7\/1002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,9]]},"references-count":255,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["biom11071002"],"URL":"https:\/\/doi.org\/10.3390\/biom11071002","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,9]]}}}