{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T13:33:33Z","timestamp":1772544813250,"version":"3.50.1"},"reference-count":106,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The EDR peptide (Glu-Asp-Arg) has been previously established to possess neuroprotective properties. It activates gene expression and synthesis of proteins, involved in maintaining the neuronal functional activity, and reduces the intensity of their apoptosis in in vitro and in vivo studies. The EDR peptide interferes with the elimination of dendritic spines in neuronal cultures obtained from mice with Alzheimer\u2019s (AD) and Huntington\u2019s diseases. The tripeptide promotes the activation of the antioxidant enzyme synthesis in the culture of cerebellum neurons in rats. The EDR peptide normalizes behavioral responses in animal studies and improves memory issues in elderly patients. The purpose of this review is to analyze the molecular and genetics aspects of the EDR peptide effect on gene expression and synthesis of proteins involved in the pathogenesis of AD. The EDR peptide is assumed to enter cells and bind to histone proteins and\/or ribonucleic acids. Thus, the EDR peptide can change the activity of the MAPK\/ERK signaling pathway, the synthesis of proapoptotic proteins (caspase-3, p53), proteins of the antioxidant system (SOD2, GPX1), transcription factors PPARA, PPARG, serotonin, calmodulin. The abovementioned signaling pathway and proteins are the components of pathogenesis in AD. The EDR peptide can be AD.<\/jats:p>","DOI":"10.3390\/molecules26010159","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T10:10:37Z","timestamp":1609409437000},"page":"159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"given":"Vladimir","family":"Khavinson","sequence":"first","affiliation":[{"name":"Department of Biogerontology, Saint Petersburg Institute of Bioregulation and Gerontology, 197110 Saint Petersburg, Russia"},{"name":"Group of Peptide Regulation of Aging, Pavlov Institute of Physiology of the Russian Academy of Sciences, 199004 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5156-5421","authenticated-orcid":false,"given":"Natalia","family":"Linkova","sequence":"additional","affiliation":[{"name":"Department of Biogerontology, Saint Petersburg Institute of Bioregulation and Gerontology, 197110 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Kozhevnikova","sequence":"additional","affiliation":[{"name":"Department of Biogerontology, Saint Petersburg Institute of Bioregulation and Gerontology, 197110 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Trofimova","sequence":"additional","affiliation":[{"name":"Department of Biogerontology, Saint Petersburg Institute of Bioregulation and Gerontology, 197110 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1055\/s-0039-1681041","article-title":"Alzheimer\u2019s Disease Including Focal Presentations","volume":"39","author":"Villain","year":"2019","journal-title":"Semin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1002\/gps.4730","article-title":"Amyloid is essential but insufficient for Alzheimer causation: Addition of subcellular cofactors is required for dementia","volume":"33","author":"Fessel","year":"2018","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"283","DOI":"10.2174\/1567205014666170417111859","article-title":"Tau in Alzheimer\u2019s Disease: Mechanisms and Therapeutic Strategies","volume":"15","author":"Gao","year":"2018","journal-title":"Curr. Alzheimer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.2147\/CIA.S105769","article-title":"Genes associated with Alzheimer\u2019s disease: An overview and current status","volume":"11","author":"Giri","year":"2016","journal-title":"Clin. Interv. Aging"},{"key":"ref_5","first-page":"35","article-title":"Effects of behaviorally active ACTH (4-10) analogue\u2014Semax on rat basal forebrain cholinergic neurons","volume":"26","author":"Grivennikov","year":"2008","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"30","DOI":"10.17116\/jnevro20181181130-36","article-title":"The efficacy of cortexin and memantinol (memantine) in the treatment of cognitive impairment in patients with chronic cerebral ischemia","volume":"118","author":"Fedin","year":"2018","journal-title":"Zhurnal Nevrol. i psikhiatrii im. S.S. Korsakova"},{"key":"ref_7","first-page":"41","article-title":"Clinical efficacy and pharmacoeconomic characteristics of the neuroprotection with low doses of cortexin in the treatment of acute ischemic stroke","volume":"114","author":"Aliferova","year":"2014","journal-title":"Zhurnal Nevrol. i psikhiatrii im. S.S. Korsakova"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s12017-017-8441-2","article-title":"Assessment of the neuroprotective effects of arginine-rich protamine peptides, poly-arginine peptides (r12-cyclic, r22) and arginine-tryptophan-containing peptides following in vitro excitotoxicity and\/or permanent middle cerebral artery occlusion in rats","volume":"19","author":"Meloni","year":"2017","journal-title":"Neuromolecular Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1586\/14737175.2016.1150180","article-title":"The neuroprotective potential of arginine-rich peptides for the acute treatment of traumatic brain injury","volume":"16","author":"Chiu","year":"2016","journal-title":"Expert Rev. Neurother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.pharmthera.2015.06.002","article-title":"Neuroprotective peptides fused to arginine-rich cell penetrating peptides: Neuroprotective mechanism likely mediated by peptide endocytic properties","volume":"153","author":"Meloni","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_11","first-page":"671","article-title":"Neuroprotective effects of peptides bioregulators in people of various age","volume":"26","author":"Umnov","year":"2013","journal-title":"Adv. Gerontol."},{"key":"ref_12","first-page":"94","article-title":"Regulation of content of cytokines in blood serum and of caspase-3 activity in brains of old rats in model of sharp hypoxic hypoxia with Cortexin and Pinealon","volume":"27","author":"Karantysh","year":"2014","journal-title":"Adv. Gerontol."},{"key":"ref_13","unstructured":"Khavinson, V.K., Grigoriev, E.I., Malinin, V.V., and Ryzhak, G.A. (2013). Tripeptide Having a Stimulating Effect on the Regeneration of Neurons Regeneration and Pharmaceutical Composition It. (194346), Israel Patent."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1089\/rej.2011.1172","article-title":"Pinealon Increases Cell Viability by Suppression of Free Radical Levels and Activating Proliferative Processes","volume":"14","author":"Khavinson","year":"2011","journal-title":"Rejuvenation Res."},{"key":"ref_15","first-page":"179","article-title":"Pinealon protects the rat offspring from prenatal hyperhomocysteinemia","volume":"5","author":"Arutjunyan","year":"2012","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/ana.25049","article-title":"Dendritic spines provide cognitive resilience against Alzheimer\u2019s disease","volume":"82","author":"Boros","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1021\/acschemneuro.8b00213","article-title":"Alzheimer\u2019s Disease, Dendritic Spines, and Calcineurin Inhibitors: A New Approach?","volume":"9","author":"Stallings","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1097\/WNR.0000000000001315","article-title":"Dendritic cell factor 1 deletion leads to developmental defects in mushroom-shaped dendritic spines","volume":"30","author":"Zheng","year":"2019","journal-title":"NeuroReport"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1007\/s10517-017-3847-2","article-title":"Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer\u2019s Disease","volume":"163","author":"Kraskovskaya","year":"2017","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1159\/000494085","article-title":"The Nuclear Translocation of Mitogen-Activated Protein Kinases: Molecular Mechanisms and Use as Novel Therapeutic Target","volume":"108","author":"Flores","year":"2019","journal-title":"Neuroendocrine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6685","DOI":"10.1038\/ncomms7685","article-title":"The nuclear translocation of ERK1\/2 as an anticancer target","volume":"6","author":"Plotnikov","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1515\/hsz-2013-0149","article-title":"Structure and function of MK5\/PRAK: The loner among the mitogen-activated protein kinase-activated protein kinases","volume":"394","author":"Moens","year":"2013","journal-title":"Biol. Chem."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s12264-013-1408-x","article-title":"Deregulation of brain insulin signaling in Alzheimer\u2019s disease","volume":"30","author":"Chen","year":"2014","journal-title":"Neurosci. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6799","DOI":"10.1523\/JNEUROSCI.5463-03.2004","article-title":"-Amyloid Peptide at Sublethal Concentrations Downregulates Brain-Derived Neurotrophic Factor Functions in Cultured Cortical Neurons","volume":"24","author":"Tong","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.pneurobio.2008.03.002","article-title":"Microtubule-associated protein tau in development, degeneration and protection of neurons","volume":"85","author":"Wang","year":"2008","journal-title":"Prog. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.tips.2008.09.001","article-title":"Oxidative stress hypothesis in Alzheimer\u2019s disease: A reappraisal","volume":"29","year":"2008","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"35789","DOI":"10.1074\/jbc.C500238200","article-title":"Hydrogen Peroxide Is Generated during the Very Early Stages of Aggregation of the Amyloid Peptides Implicated in Alzheimer Disease and Familial British Dementia","volume":"280","author":"Tabner","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2174\/138920109787847501","article-title":"Calcium-Sensing Receptor (CaSR) in Human Brains Pathophysiology: Roles in Late-Onset Alzheimers Disease (LOAD)","volume":"10","author":"Chiarini","year":"2009","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1365-2990.2004.00569.x","article-title":"Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK\/JNK-P) and p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding \u03b2A plaques in APP Tg2576 mice","volume":"30","author":"Puig","year":"2004","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17721","DOI":"10.1074\/jbc.M800013200","article-title":"Hydrogen peroxide promotes A\u03b2 production through JNK-dependent activation of \u03b3-secretase","volume":"283","author":"Shen","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.nbd.2008.12.014","article-title":"JNK regulates APP cleavage and degradation in a model of Alzheimer\u2019s disease","volume":"33","author":"Colombo","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1091\/mbc.e06-07-0625","article-title":"The Amyloid-\u03b2 Precursor Protein Is Phosphorylated via Distinct Pathways during Differentiation, Mitosis, Stress, and Degeneration","volume":"18","author":"Muresan","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_34","first-page":"957","article-title":"ASK1-MAP kinase signaling pathway as a therapeutic target for human diseases","volume":"72","author":"Fujisawa","year":"2014","journal-title":"Nihon Rinsho"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1385\/NMM:5:3:205","article-title":"Tau phosphorylation in Alzheimer\u2019s disease: Potential involvement of an APP-MAP kinase complex","volume":"5","author":"Peel","year":"2004","journal-title":"Neuromolecular Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.nbd.2007.06.017","article-title":"Interaction of ASK1 and the \u03b2-amyloid precursor protein in a stress-signaling complex","volume":"28","author":"Galvan","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/j.neurobiolaging.2007.12.015","article-title":"JNK and ERK1\/2 pathways have a dual opposite effect on the expression of BACE1","volume":"30","author":"Tamagno","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9304","DOI":"10.1128\/MCB.25.21.9304-9317.2005","article-title":"Transforming Growth Factor \u03b22 Is a Neuronal Death-Inducing Ligand for Amyloid-\u03b2 Precursor Protein","volume":"25","author":"Hashimoto","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.bbadis.2009.12.009","article-title":"Pathological roles of MAPK signaling pathways in human diseases","volume":"1802","author":"Kim","year":"2010","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_40","unstructured":"Tomasi, A. (2003). Significance of reactive oxygen species for neuronal function. Free Radicals, NO, and Inflammation: Molecular, Biochemical and Clinical Aspects, IOS Press."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1089\/ars.2007.9.233","article-title":"Sources and Targets of Reactive Oxygen Species in Synaptic Plasticity and Memory","volume":"9","author":"Kishida","year":"2006","journal-title":"Antioxidants Redox Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s10517-015-2906-9","article-title":"Peptide Regulation of Cells Renewal Processes in Kidney Tissue Cultures from Young and Old Animals","volume":"159","author":"Chalisova","year":"2015","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s10517-014-2540-y","article-title":"Peptides Regulate Expression of Signaling Molecules in Kidney Cell Cultures during In Vitro Aging","volume":"157","author":"Khavinson","year":"2014","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s10517-014-2713-8","article-title":"Molecular Aspects of Anti-Atherosclerotic Effects of Short Peptides","volume":"158","author":"Khavinson","year":"2014","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s10517-011-1298-8","article-title":"Peptidergic Regulation of Thymocyte Differentiation, Proliferation, and Apoptosis during Aging of the Thymus","volume":"151","author":"Linkova","year":"2011","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10517-016-3370-x","article-title":"Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro","volume":"161","author":"Orlova","year":"2016","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.7150\/ijms.36516","article-title":"Potential for therapeutic use of hydrogen sulfide in oxidative stress-induced neurodegenerative diseases","volume":"16","author":"Tabassum","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ijdevneu.2004.07.006","article-title":"Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576 mice with Alzheimer-like pathology","volume":"22","author":"Apelt","year":"2004","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.freeradbiomed.2004.12.020","article-title":"Selective neuronal vulnerability and inadequate stress response in superoxide dismutase mutant mice","volume":"38","author":"Lynn","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1523\/JNEUROSCI.0482-06.2006","article-title":"Reduction in Mitochondrial Superoxide Dismutase Modulates Alzheimer\u2019s Disease-Like Pathology and Accelerates the Onset of Behavioral Changes in Human Amyloid Precursor Protein Transgenic Mice","volume":"26","author":"Esposito","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5589","DOI":"10.1523\/JNEUROSCI.6566-10.2011","article-title":"Amyloid -Induced Impairments in Hippocampal Synaptic Plasticity Are Rescued by Decreasing Mitochondrial Superoxide","volume":"31","author":"Ma","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Melov, S., Adlard, P.A., Morten, K., Johnson, F., Golden, T.R., Hinerfeld, D., Schilling, B., Mavros, C., Masters, C.L., and Volitakis, I. (2007). Mitochondrial oxidative stress causes hyperphosphorylation of tau. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000536"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Himori, K., Abe, M., Tatebayashi, D., Lee, J., Westerblad, H., Lanner, J.T., and Yamada, T. (2017). Superoxide dismutase\/catalase mimetic EUK-134 prevents diaphragm muscle weakness in monocrotalin-induced pulmonary hypertension. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169146"},{"key":"ref_54","first-page":"72","article-title":"Glutathione Peroxidase 1 Pro198Leu Polymorphism in Brazilian Alzheimer\u2019s Disease Patients: Relations to the Enzyme Activity and to Selenium Status","volume":"5","author":"Cardoso","year":"2012","journal-title":"J. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1017\/S0007114509992832","article-title":"Nutritional status of selenium in Alzheimer\u2019s disease patients","volume":"103","author":"Cardoso","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1134\/S001249660603001X","article-title":"Carnosine protects from the oxidative stress induced by prenatal hypoxia","volume":"408","author":"Fedorova","year":"2006","journal-title":"Dokl. Biol. Sci."},{"key":"ref_57","first-page":"1","article-title":"Regulatory peptides protect brain neurons from hypoxia in vivo","volume":"418","author":"Kozina","year":"2007","journal-title":"Dokl. Biol. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.canlet.2013.12.025","article-title":"Tumor suppressor p53 and its mutants in cancer metabolism","volume":"356","author":"Liu","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"545","DOI":"10.18632\/aging.100205","article-title":"Unfolded p53 in the pathogenesis of Alzheimer\u2019s disease: Is HIPK2 the link?","volume":"2","author":"Stanga","year":"2010","journal-title":"Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.pneurobio.2018.05.001","article-title":"The interactions of p53 with tau and A\u00df as potential therapeutic targets for Alzheimer\u2019s disease","volume":"168","author":"Jembrek","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000329999","article-title":"Role of p53 in Neurodegenerative Diseases","volume":"9","author":"Chang","year":"2011","journal-title":"Neurodegener. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.2174\/1568026617666170103161233","article-title":"Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players","volume":"17","author":"Gasiorowski","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S1097-2765(03)00050-9","article-title":"p53 Has a Direct Apoptogenic Role at the Mitochondria","volume":"11","author":"Mihara","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1089\/ars.2011.4124","article-title":"Lack of p53 Decreases Basal Oxidative Stress Levels in the Brain Through Upregulation of Thioredoxin-1, Biliverdin Reductase-A, Manganese Superoxide Dismutase, and Nuclear Factor Kappa-B","volume":"16","author":"Barone","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1002\/jnr.23627","article-title":"Basal brain oxidative and nitrative stress levels are finely regulated by the interplay between superoxide dismutase 2 and p53","volume":"93","author":"Barone","year":"2015","journal-title":"J. Neurosci. Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Fiorini, A., Sultana, R., Barone, E., Cenini, G., Perluigi, M., Mancuso, C., Cai, J., Klein, J.B., Clair, D.S., and Butterfield, D.A. (2012). Lack of p53 Affects the Expression of Several Brain Mitochondrial Proteins: Insights from Proteomics into Important Pathways Regulated by p53. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049846"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3233\/JAD-2006-9S331","article-title":"Lysosomal system pathways: Genes to neurodegeneration in Alzheimer\u2019s disease","volume":"9","author":"Nixon","year":"2006","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s11055-006-0092-y","article-title":"Long-term potentiation in the hippocampus in conditions of inhibition of caspase-3: Analysis of facilitation in paired-pulse stimulation","volume":"36","author":"Kudryashova","year":"2006","journal-title":"Neurosci. Behav. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/74656","article-title":"A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor","volume":"6","author":"Lu","year":"2000","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.nbd.2003.07.006","article-title":"Accumulation of caspase cleaved amyloid precursor protein represents an early neurodegenerative event in aging and in Alzheimer\u2019s disease","volume":"14","author":"Zhao","year":"2003","journal-title":"Neurobiol. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0006-8993(01)02018-2","article-title":"Activated caspase-3 expression in Alzheimer\u2019s and aged control brain: Correlation with Alzheimer pathology","volume":"898","author":"Su","year":"2001","journal-title":"Brain Res."},{"key":"ref_72","first-page":"69","article-title":"Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer\u2019s disease","volume":"14","author":"Cavallucci","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/mp.2016.214","article-title":"Caspase-3-dependent cleavage of Akt modulates tau phosphorylation via GSK3\u03b2 kinase: Implications for Alzheimer\u2019s disease","volume":"22","author":"Chu","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_74","first-page":"252","article-title":"Effect of peptide geroprotectors on the navigation system learning and caspase-3 in brain structures in rats of different age","volume":"26","author":"Mendzheritski","year":"2013","journal-title":"Adv. Gerontol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/1742-2094-8-164","article-title":"Systemic inflammatory challenges compromise survival after experimental stroke via augmenting brain inflammation, blood-brain barrier damage and brain oedema independently of infarct size","volume":"8","author":"Denes","year":"2011","journal-title":"J. Neuroinflammation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/1423-0127-20-90","article-title":"Caspase 3 involves in neuroplasticity, microglial activation and neurogenesis in the mice hippocampus after intracerebral injection of kainic acid","volume":"20","author":"Tzeng","year":"2013","journal-title":"J. Biomed. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-018-1313-3","article-title":"Inflammation: The link between comorbidities, genetics, and Alzheimer\u2019s disease","volume":"15","author":"Newcombe","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1523\/JNEUROSCI.20-02-00558.2000","article-title":"Inflammatory Mechanisms in Alzheimer\u2019s Disease: Inhibition of \u03b2-Amyloid-Stimulated Proinflammatory Responses and Neurotoxicity by PPAR\u03b3 Agonists","volume":"20","author":"Combs","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_79","first-page":"39","article-title":"Interactions between PPAR-\u03b1 and inflammation-related cytokine genes on the development of Alzheimer\u2019s disease, observed by the Epistasis Project","volume":"3","author":"Heun","year":"2012","journal-title":"Int. J. Mol. Epidemiol. Genet"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0197-0186(01)00052-3","article-title":"Regulation of \u03b2-amyloid stimulated proinflammatory responses by peroxisome proliferator-activated receptor \u03b1","volume":"39","author":"Combs","year":"2001","journal-title":"Neurochem. Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0165-0173(95)00011-9","article-title":"The inflammatory response system of brain: Implications for therapy of Alzheimer and other neurodegenerative diseases","volume":"21","author":"McGeer","year":"1995","journal-title":"Brain Res. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3233\/JAD-2006-9209","article-title":"Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer\u2019s disease","volume":"9","author":"Wands","year":"2006","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"8445","DOI":"10.1073\/pnas.1504890112","article-title":"Activation of peroxisome proliferator-activated receptor \u03b1 stimulates ADAM10-mediated proteolysis of APP","volume":"112","author":"Corbett","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1212\/01.WNL.0000091890.32140.8F","article-title":"Plasma A 40 and A 42 and Alzheimer\u2019s disease: Relation to age, mortality, and risk","volume":"61","author":"Mayeux","year":"2003","journal-title":"Neurology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s12603-016-0794-y","article-title":"Gene- gene interaction between PPARG and APOE gene on late-onset Alzheimer\u2019s disease: A case- control study in Chinese han population","volume":"21","author":"Wang","year":"2016","journal-title":"J. Nutr. Health Aging"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1159\/000095857","article-title":"Association Analysis of Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms and Late Onset Alzheimer\u2019s Disease in the Finnish Population","volume":"22","author":"Koivisto","year":"2006","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1073\/pnas.0503839103","article-title":"Nonsteroidal anti-inflammatory drugs repress -secretase gene promoter activity by the activation of PPAR","volume":"103","author":"Sastre","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s10517-014-2496-y","article-title":"Short Peptides Stimulate Serotonin Expression in Cells of Brain Cortex","volume":"157","author":"Khavinson","year":"2014","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21767\/2171-6625.1000166","article-title":"Neuroprotective effect of EDR peptide in mouse model of huntington\u2019s disease","volume":"8","author":"Khavinson","year":"2017","journal-title":"J. Neurol. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Vigliante, I., Mannino, G., and Maffei, M.E. (2019). Chemical Characterization and DNA Fingerprinting of Griffonia simplicifolia Baill. Molecules, 24.","DOI":"10.3390\/molecules24061032"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3389\/fnagi.2017.00087","article-title":"Genetics of Aggression in Alzheimer\u2019s Disease (AD)","volume":"9","author":"Lukiw","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"101800","DOI":"10.1016\/j.pneurobio.2020.101800","article-title":"Tryptophan metabolites modify brain A\u03b2 peptide degradation: A role in Alzheimer\u2019s disease?","volume":"190","author":"Maitre","year":"2020","journal-title":"Prog. Neurobiol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Hornedo-Ortega, R., Da Costa, G., Cerezo, A.B., Troncoso, A.M., Richard, T., and Garc\u00eda-Parrilla, M.C. (2018). In Vitro Effects of Serotonin, Melatonin, and Other Related Indole Compounds on Amyloid-\u03b2 Kinetics and Neuroprotection. Mol. Nutr. Food Res., 62.","DOI":"10.1002\/mnfr.201700383"},{"key":"ref_94","first-page":"836","article-title":"Optogenetic stimulation of serotonin nuclei retrieve the lost memory in Alzheimer\u2019s disease","volume":"235","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0006-8993(90)90342-9","article-title":"Evidence for decreased transport of tryptophan hydroxylase in Alzheimer\u2019s disease","volume":"537","author":"Burke","year":"1990","journal-title":"Brain Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.pneurobio.2016.03.007","article-title":"How serotonin receptors regulate morphogenic signalling in neurons","volume":"151","author":"Wirth","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_97","first-page":"77","article-title":"The role of serotonin receptors in Alzheimer\u2019s disease","volume":"2","author":"Butzlaff","year":"2016","journal-title":"Opera Med. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1097\/HRP.0000000000000097","article-title":"Interventions for Neuropsychiatric Symptoms in Neurocognitive Impairment Due to Alzheimer\u2019s Disease","volume":"23","author":"McClam","year":"2015","journal-title":"Harv. Rev. Psychiatry"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1176\/appi.ajp.2015.15050648","article-title":"Heterogeneity of Treatment Response to Citalopram for Patients With Alzheimer\u2019s Disease With Aggression or Agitation: The CitAD Randomized Clinical Trial","volume":"173","author":"Schneider","year":"2016","journal-title":"Am. J. Psychiatry"},{"key":"ref_100","first-page":"236re4","article-title":"An Antidepressant Decreases CSF A Production in Healthy Individuals and in Transgenic AD Mice","volume":"6","author":"Sheline","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s10517-016-3596-7","article-title":"Short Peptides Regulate Gene Expression","volume":"162","author":"Khavinson","year":"2016","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1134\/S0026893319020092","article-title":"Epigenetic mechanisms of peptide-driven regulation and neuroprotective protein FKBP1b","volume":"53","author":"Kuznik","year":"2019","journal-title":"Mol. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"10553","DOI":"10.1093\/nar\/gkz850","article-title":"Systematic search for structural motifs of peptide binding to double-stranded DNA","volume":"47","author":"Kolchina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s10522-009-9249-8","article-title":"Peptide bioregulation of aging: Results and prospects","volume":"11","author":"Anisimov","year":"2010","journal-title":"Biogerontology"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Khavinson, V., Linkova, N.S., Dyatlova, A., Kuznik, B.I., and Umnov, R. (2020). Peptides: Prospects for use in the treatment of COVID-19. J. Mol. Spec. Issue, 25.","DOI":"10.3390\/molecules25194389"},{"key":"ref_106","first-page":"1210","article-title":"Penetration of short fluorescence labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA","volume":"76","author":"Fedoreyeva","year":"2011","journal-title":"Biochemistry"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/1\/159\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:48:39Z","timestamp":1760179719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/1\/159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,31]]},"references-count":106,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["molecules26010159"],"URL":"https:\/\/doi.org\/10.3390\/molecules26010159","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,31]]}}}