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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Research Article

Co-ultraPEALut: Role in Preclinical and Clinical Delirium Manifestations

Author(s): Maria Lia Lunardelli, Rosalia Crupi, Rosalba Siracusa, Giorgio Cocuzza, Marika Cordaro, Emilio Martini, Daniela Impellizzeri, Rosanna Di Paola and Salvatore Cuzzocrea*

Volume 18, Issue 7, 2019

Page: [530 - 554] Pages: 25

DOI: 10.2174/1871527318666190617162041

Price: $65

Abstract

Background: Delirium is a disorder in awareness, attention and cognition. Pathophysiologically it is a response to stress. Postoperative delirium (POD) is a usual complication in aged patients following hip fracture surgery. Neuroinflammation is an important factor linked with the progress of POD. Though there are no efficient cures for delirium the endocannabinoid system may have a role in neuropsychiatric disorders.

Objective: Therefore, we examined the effects of co-ultramicronized PEALut (co-ultraPEALut) in the LPS murine model of delirium and in elderly hip fractured patients.

Methods: In the preclinical study, mice were injected intraperitoneally (i.p.) with Escherichia coli LPS (10 mg/kg). Co-ultraPEALut (1 mg/kg o.s.) was administered 1h before LPS injection or 1h and 6h after LPS injection or 1h before LPS injection and 1h and 6h after LPS. In the clinical study, the effects of Glialia® (co-ultramicronized 700 mg PEA + 70 mg luteolin) administration was evaluated in elderly hip fractured patients with an interventional, randomized, single-blind, monocentric study.

Results: Administration of co-ultraPEALut to LPS-challenged mice ameliorated cognitive dysfunctions and locomotor activity; moreover, it reduced inflammation and apoptosis, while stimulating antioxidant response and limiting the loss of neurotrophins. In the clinical study, the results obtained demonstrated that administration of Glialia® to these surgical patients prevented the onset of POD and attenuated symptom intensity and their duration.

Conclusion: Therefore, the results obtained enhanced the idea that co-ultraPEALut may be a potential treatment to control cognitive impairment and the inflammatory and oxidative processes associated with delirium.

Keywords: Delirium, mice, neuroinflammation, luteolin, palmitoylethanolamide, patients.

Graphical Abstract

[1]
Tandon R. Schizophrenia and other psychotic disorders in diagnostic and statistical manual of mental disorders (DSM)-5: Clinical implications of revisions from DSM-IV. Indian J Psychol Med 2014; 36(3): 223-5.
[http://dx.doi.org/10.4103/0253-7176.135365] [PMID: 25035542]
[2]
Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet 2014; 383(9920): 911-22.
[http://dx.doi.org/10.1016/S0140-6736(13)60688-1] [PMID: 23992774]
[3]
Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 1996; 275(11): 852-7.
[http://dx.doi.org/10.1001/jama.1996.03530350034031] [PMID: 8596223]
[4]
Guo Y, Jia P, Zhang J, Wang X, Jiang H, Jiang W. Prevalence and risk factors of postoperative delirium in elderly hip fracture patients. J Int Med Res 2016; 44(2): 317-27.
[http://dx.doi.org/10.1177/0300060515624936] [PMID: 26920926]
[5]
Yang Y, Zhao X, Dong T, Yang Z, Zhang Q, Zhang Y. Risk factors for postoperative delirium following hip fracture repair in elderly patients: A systematic review and meta-analysis. Aging Clin Exp Res 2017; 29(2): 115-26.
[http://dx.doi.org/10.1007/s40520-016-0541-6] [PMID: 26873816]
[6]
Inouye SK, Robinson T, Blaum C, et al. American Geriatrics Society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc 2015; 63(1): 142-50.
[http://dx.doi.org/10.1111/jgs.13281] [PMID: 25495432]
[7]
Wang NY, Hirao A, Sieber F. Association between intraoperative blood pressure and postoperative delirium in elderly hip fracture patients. PLoS One 2015; 10(4)e0123892
[http://dx.doi.org/10.1371/journal.pone.0123892] [PMID: 25860338]
[8]
Zywiel MG, Hurley RT, Perruccio AV, Hancock-Howard RL, Coyte PC, Rampersaud YR. Health economic implications of perioperative delirium in older patients after surgery for a fragility hip fracture. J Bone Joint Surg Am 2015; 97(10): 829-36.
[http://dx.doi.org/10.2106/JBJS.N.00724] [PMID: 25995494]
[9]
Witlox J, Eurelings LSM, de Jonghe JFM, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: A meta-analysis. JAMA 2010; 304(4): 443-51.
[http://dx.doi.org/10.1001/jama.2010.1013] [PMID: 20664045]
[10]
Cerejeira J, Firmino H, Vaz-Serra A, Mukaetova-Ladinska EB. The neuroinflammatory hypothesis of delirium. Acta Neuropathol 2010; 119(6): 737-54.
[http://dx.doi.org/10.1007/s00401-010-0674-1] [PMID: 20309566]
[11]
Dillon ST, Vasunilashorn SM, Ngo L, et al. Higher C-reactive protein levels predict postoperative delirium in older patients undergoing major elective surgery: A longitudinal nested case-control study. Biol Psychiatry 2017; 81(2): 145-53.
[http://dx.doi.org/10.1016/j.biopsych.2016.03.2098] [PMID: 27160518]
[12]
Teeling JL, Perry VH. Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: Underlying mechanisms. Neuroscience 2009; 158(3): 1062-73.
[http://dx.doi.org/10.1016/j.neuroscience.2008.07.031] [PMID: 18706982]
[13]
Murray C, Sanderson DJ, Barkus C, et al. Systemic inflammation induces acute working memory deficits in the primed brain: Relevance for delirium. Neurobiol Aging 2012; 33(3): 603-16. e3.
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.04.002]
[14]
Bellinger FP, Madamba S, Siggins GR. Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus. Brain Res 1993; 628(1-2): 227-34.
[http://dx.doi.org/10.1016/0006-8993(93)90959-Q] [PMID: 8313151]
[15]
Cunningham AJ, Murray CA, O’Neill LA, Lynch MA, O’Connor JJ. Interleukin-1 beta (IL-1 beta) and Tumour Necrosis Factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro. Neurosci Lett 1996; 203(1): 17-20.
[http://dx.doi.org/10.1016/0304-3940(95)12252-4] [PMID: 8742036]
[16]
Tancredi V, D’Antuono M, Cafè C, et al. The inhibitory effects of interleukin-6 on synaptic plasticity in the rat hippocampus are associated with an inhibition of mitogen-activated protein kinase ERK. J Neurochem 2000; 75(2): 634-43.
[http://dx.doi.org/10.1046/j.1471-4159.2000.0750634.x] [PMID: 10899938]
[17]
Hellstrom IC, Danik M, Luheshi GN, Williams S. Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-beta-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neurons. Hippocampus 2005; 15(5): 656-64.
[http://dx.doi.org/10.1002/hipo.20086] [PMID: 15889405]
[18]
Shaw KN, Commins S, O’Mara SM. Cyclooxygenase inhibition attenuates endotoxin-induced spatial learning deficits, but not an endotoxin-induced blockade of long-term potentiation. Brain Res 2005; 1038(2): 231-7.
[http://dx.doi.org/10.1016/j.brainres.2005.01.035] [PMID: 15757639]
[19]
Palin K, Bluthé RM, Verrier D, Tridon V, Dantzer R, Lestage J. Interleukin-1beta mediates the memory impairment associated with a delayed type hypersensitivity response to Bacillus Calmette-Guérin in the rat hippocampus. Brain Behav Immun 2004; 18(3): 223-30.
[http://dx.doi.org/10.1016/j.bbi.2003.09.002] [PMID: 15050649]
[20]
Rosi S, Ramirez-Amaya V, Vazdarjanova A, Worley PF, Barnes CA, Wenk GL. Neuroinflammation alters the hippocampal pattern of behaviorally induced Arc expression. J Neurosci 2005; 25(3): 723-31.
[http://dx.doi.org/10.1523/JNEUROSCI.4469-04.2005] [PMID: 15659610]
[21]
Tanaka S, Ide M, Shibutani T, et al. Lipopolysaccharide-induced microglial activation induces learning and memory deficits without neuronal cell death in rats. J Neurosci Res 2006; 83(4): 557-66.
[http://dx.doi.org/10.1002/jnr.20752] [PMID: 16429444]
[22]
Siddiqi N, Harrison JK, Clegg A, et al. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev 2016; 3CD005563
[http://dx.doi.org/10.1002/14651858.CD005563.pub3] [PMID: 26967259]
[23]
Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: A systematic review and meta-analysis. J Am Geriatr Soc 2016; 64(4): 705-14.
[http://dx.doi.org/10.1111/jgs.14076] [PMID: 27004732]
[24]
Orsolini L, Papanti D, Corkery J, et al. Is there a teratogenicity risk associated with cannabis and synthetic cannabimimetics’ (‘Spice’) intake? CNS Neurol Disord Drug Targets 2017; 16(5): 585-91.
[http://dx.doi.org/10.2174/1871527316666170413101257] [PMID: 28412917]
[25]
Romaguera A, Torrens M, Papaseit E, Arellano AL, Farré M. Concurrent use of cannabis and alcohol: Neuropsychiatric effect consequences. CNS Neurol Disord Drug Targets 2017; 16(5): 592-7.
[http://dx.doi.org/10.2174/1871527316666170419161839] [PMID: 28440194]
[26]
Mannucci C, Navarra M, Calapai F, et al. Neurological aspects of medical use of cannabidiol. CNS Neurol Disord Drug Targets 2017; 16(5): 541-53.
[http://dx.doi.org/10.2174/1871527316666170413114210] [PMID: 28412918]
[27]
Healy-Stoffel M, Levant B. N-3 (Omega-3) Fatty acids: Effects on brain dopamine systems and potential role in the etiology and treatment of neuropsychiatric disorders. CNS Neurol Disord Drug Targets 2018; 17(3): 216-32.
[http://dx.doi.org/10.2174/1871527317666180412153612] [PMID: 29651972]
[28]
Filiou MD, Banati RB, Graeber MB. The 18-kDa translocator protein as a CNS drug target: Finding our way through the neuroinflammation fog. CNS Neurol Disord Drug Targets 2017; 16(9): 990-9.
[PMID: 28982340]
[29]
Vazquez GH, Camino S, Tondo L, Baldessarini RJ. Potential novel treatments for bipolar depression: Ketamine, fatty acids, anti-inflammatory agents, and probiotics. CNS Neurol Disord Drug Targets 2017; 16(8): 858-69.
[PMID: 28758582]
[30]
Murillo-Rodriguez E, Pastrana-Trejo JC, Salas-Crisóstomo M, de-la-Cruz M. The endocannabinoid system modulating levels of consciousness, emotions and likely dream contents. CNS Neurol Disord Drug Targets 2017; 16(4): 370-9.
[http://dx.doi.org/10.2174/1871527316666170223161908] [PMID: 28240187]
[31]
Arellano AL, Papaseit E, Romaguera A, Torrens M, Farré M. Neuropsychiatric and general interactions of natural and synthetic cannabinoids with drugs of abuse and medicines. CNS Neurol Disord Drug Targets 2017; 16(5): 554-66.
[http://dx.doi.org/10.2174/1871527316666170413104516] [PMID: 28412920]
[32]
Skaper SD, Facci L, Fusco M, et al. Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. Inflammopharmacology 2014; 22(2): 79-94.
[http://dx.doi.org/10.1007/s10787-013-0191-7] [PMID: 24178954]
[33]
Mattace Raso G, Russo R, Calignano A, Meli R. Palmitoylethanolamide in CNS health and disease. Pharmacol Res 2014; 86: 32-41.
[http://dx.doi.org/10.1016/j.phrs.2014.05.006] [PMID: 24844438]
[34]
Guo DJ, Li F, Yu PH, Chan SW. Neuroprotective effects of luteolin against apoptosis induced by 6-hydroxydopamine on rat pheochromocytoma PC12 cells. Pharm Biol 2013; 51(2): 190-6.
[http://dx.doi.org/10.3109/13880209.2012.716852] [PMID: 23035972]
[35]
Guerra-Araiza C, Álvarez-Mejía AL, Sánchez-Torres S, et al. Effect of natural exogenous antioxidants on aging and on neurodegenerative diseases. Free Radic Res 2013; 47(6-7): 451-62.
[http://dx.doi.org/10.3109/10715762.2013.795649] [PMID: 23594291]
[36]
Zhao G, Zang SY, Jiang ZH, et al. Postischemic administration of liposome-encapsulated luteolin prevents against ischemia-reperfusion injury in a rat middle cerebral artery occlusion model. J Nutr Biochem 2011; 22(10): 929-36.
[http://dx.doi.org/10.1016/j.jnutbio.2010.07.014] [PMID: 21190830]
[37]
Impellizzeri D, Bruschetta G, Cordaro M, et al. Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain. J Neuroinflammation 2014; 11: 136.
[http://dx.doi.org/10.1186/s12974-014-0136-0] [PMID: 25164769]
[38]
Onesti E, Frasca V, Ceccanti M, et al. Short-term ultramicronized palmitoylethanolamide therapy in patients with Myasthenia Gravis: A pilot study to possible future implications of treatment. CNS Neurol Disord Drug Targets 2019; 18(3): 232-8.
[http://dx.doi.org/10.2174/1871527318666190131121827] [PMID: 30706796]
[39]
Siracusa R, Paterniti I, Impellizzeri D, et al. The association of palmitoylethanolamide with luteolin decreases neuroinflammation and stimulates autophagy in Parkinson’s Disease model. CNS Neurol Disord Drug Targets 2015; 14(10): 1350-65.
[http://dx.doi.org/10.2174/1871527314666150821102823] [PMID: 26295827]
[40]
Caltagirone C, Cisari C, Schievano C, et al. Co-ultramicronized palmitoylethanolamide/luteolin in the treatment of cerebral ischemia: From rodent to man. Transl Stroke Res 2016; 7(1): 54-69.
[http://dx.doi.org/10.1007/s12975-015-0440-8] [PMID: 26706245]
[41]
Bhaskar K, Konerth M, Kokiko-Cochran ON, Cardona A, Ransohoff RM, Lamb BT. Regulation of tau pathology by the microglial fractalkine receptor. Neuron 2010; 68(1): 19-31.
[http://dx.doi.org/10.1016/j.neuron.2010.08.023] [PMID: 20920788]
[42]
Laflamme N, Soucy G, Rivest S. Circulating cell wall components derived from gram-negative, not gram-positive, bacteria cause a profound induction of the gene-encoding Toll-like receptor 2 in the CNS. J Neurochem 2001; 79(3): 648-57.
[http://dx.doi.org/10.1046/j.1471-4159.2001.00603.x] [PMID: 11701768]
[43]
Cordaro M, Impellizzeri D, Paterniti I, et al. Neuroprotective effects of Co-UltraPEALut on secondary inflammatory process and autophagy involved in traumatic brain injury. J Neurotrauma 2016; 33(1): 132-46.
[http://dx.doi.org/10.1089/neu.2014.3460] [PMID: 25046306]
[44]
Porsolt RD, Bertin A, Blavet N, Deniel M, Jalfre M. Immobility induced by forced swimming in rats: Effects of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol 1979; 57(2-3): 201-10.
[http://dx.doi.org/10.1016/0014-2999(79)90366-2] [PMID: 488159]
[45]
Pellow S, Chopin P, File SE, Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 1985; 14(3): 149-67.
[http://dx.doi.org/10.1016/0165-0270(85)90031-7] [PMID: 2864480]
[46]
Moy SS, Nadler JJ, Young NB, et al. Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains. Behav Brain Res 2007; 176(1): 4-20.
[http://dx.doi.org/10.1016/j.bbr.2006.07.030] [PMID: 16971002]
[47]
Deacon RM, Bannerman DM, Kirby BP, Croucher A, Rawlins JN. Effects of cytotoxic hippocampal lesions in mice on a cognitive test battery. Behav Brain Res 2002; 133(1): 57-68.
[http://dx.doi.org/10.1016/S0166-4328(01)00451-X] [PMID: 12048174]
[48]
Reisel D, Bannerman DM, Schmitt WB, et al. Spatial memory dissociations in mice lacking GluR1. Nat Neurosci 2002; 5(9): 868-73.
[http://dx.doi.org/10.1038/nn910] [PMID: 12195431]
[49]
von Engelhardt J, Doganci B, Jensen V, et al. Contribution of hippocampal and extra-hippocampal NR2B-containing NMDA receptors to performance on spatial learning tasks. Neuron 2008; 60(5): 846-60.
[http://dx.doi.org/10.1016/j.neuron.2008.09.039] [PMID: 19081379]
[50]
Fujii M, Hara H, Meng W, Vonsattel JP, Huang Z, Moskowitz MA. Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57black/6 mice. Stroke 1997; 28(9): 1805-10.
[http://dx.doi.org/10.1161/01.STR.28.9.1805] [PMID: 9303029]
[51]
Heeneman S, Sluimer JC, Daemen MJ. Angiotensin-converting enzyme and vascular remodeling. Circ Res 2007; 101(5): 441-54.
[http://dx.doi.org/10.1161/CIRCRESAHA.107.148338] [PMID: 17761934]
[52]
Crupi R, Paterniti I, Campolo M, Di Paola R, Cuzzocrea S, Esposito E. Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury. Pharmacol Res 2013; 70(1): 80-9.
[http://dx.doi.org/10.1016/j.phrs.2012.12.009] [PMID: 23313345]
[53]
Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162(1): 156-9.
[http://dx.doi.org/10.1016/0003-2697(87)90021-2] [PMID: 2440339]
[54]
Bellelli G, Morandi A, Davis DH, et al. Validation of the 4AT, a new instrument for rapid delirium screening: A study in 234 hospitalised older people. Age Ageing 2014; 43(4): 496-502.
[http://dx.doi.org/10.1093/ageing/afu021] [PMID: 24590568]
[55]
de Jonghe JF, Kalisvaart KJ, Timmers JF, Kat MG, Jackson JC. Delirium-O-Meter: A nurses’ rating scale for monitoring delirium severity in geriatric patients. Int J Geriatr Psychiatry 2005; 20(12): 1158-66.
[http://dx.doi.org/10.1002/gps.1410] [PMID: 16315151]
[56]
Partridge JS, Martin FC, Harari D, Dhesi JK. The delirium experience: What is the effect on patients, relatives and staff and what can be done to modify this? Int J Geriatr Psychiatry 2013; 28(8): 804-12.
[http://dx.doi.org/10.1002/gps.3900] [PMID: 23112139]
[57]
MacLullich AM, Hall RJ. Who understands delirium? Age Ageing 2011; 40(4): 412-4.
[http://dx.doi.org/10.1093/ageing/afr062] [PMID: 21636556]
[58]
Amodeo G, Fagiolini A, Sachs G, Erfurth A. Older and newer strategies for the pharmacological management of agitation in patients with bipolar disorder or schizophrenia. CNS Neurol Disord Drug Targets 2017; 16(8): 885-90.
[PMID: 28933260]
[59]
Cunningham C, Campion S, Lunnon K, et al. Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry 2009; 65(4): 304-12.
[http://dx.doi.org/10.1016/j.biopsych.2008.07.024] [PMID: 18801476]
[60]
Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci 2004; 5(5): 347-60.
[http://dx.doi.org/10.1038/nrn1387] [PMID: 15100718]
[61]
Finucane DM, Bossy-Wetzel E, Waterhouse NJ, Cotter TG, Green DR. Bax-induced caspase activation and apoptosis via cytochrome c release from mitochondria is inhibitable by Bcl-xL. J Biol Chem 1999; 274(4): 2225-33.
[http://dx.doi.org/10.1074/jbc.274.4.2225] [PMID: 9890985]
[62]
Kowaltowski AJ, Fenton RG, Fiskum G. Bcl-2 family proteins regulate mitochondrial reactive oxygen production and protect against oxidative stress. Free Radic Biol Med 2004; 37(11): 1845-53.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.09.005] [PMID: 15528043]
[63]
Yuan Y, Fang M, Wu CY, Ling EA. Scutellarin as a potential therapeutic agent for microglia-mediated neuroinflammation in cerebral ischemia. Neuromolecular Med 2016; 18(3): 264-73.
[http://dx.doi.org/10.1007/s12017-016-8394-x] [PMID: 27103430]
[64]
Alcendor RR, Gao S, Zhai P, et al. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res 2007; 100(10): 1512-21.
[http://dx.doi.org/10.1161/01.RES.0000267723.65696.4a] [PMID: 17446436]
[65]
Salminen A, Kauppinen A, Suuronen T, Kaarniranta K. SIRT1 longevity factor suppresses NF-kappaB -driven immune responses: Regulation of aging via NF-kappaB acetylation? BioEssays 2008; 30(10): 939-42.
[http://dx.doi.org/10.1002/bies.20799] [PMID: 18800364]
[66]
Rajendran R, Garva R, Krstic-Demonacos M, Demonacos C. Sirtuins: Molecular traffic lights in the crossroad of oxidative stress, chromatin remodeling, and transcription. J Biomed Biotechnol 2011; 2011368276
[http://dx.doi.org/10.1155/2011/368276] [PMID: 21912480]
[67]
Picard F, Kurtev M, Chung N, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004; 429(6993): 771-6.
[http://dx.doi.org/10.1038/nature02583] [PMID: 15175761]
[68]
Corpas R, Revilla S, Ursulet S, et al. SIRT1 Overexpression in mouse hippocampus induces cognitive enhancement through proteostatic and neurotrophic mechanisms. Mol Neurobiol 2017; 54(7): 5604-19.
[http://dx.doi.org/10.1007/s12035-016-0087-9] [PMID: 27614878]
[69]
Han J, Liu X, Li Y, Zhang J, Yu H. Sirt1/Nrf2 signalling pathway prevents cognitive impairment in diabetic rats through anti-oxidative stress induced by miRNA-23b-3p expression. Mol Med Rep 2018; 17(6): 8414-22.
[http://dx.doi.org/10.3892/mmr.2018.8876] [PMID: 29658582]
[70]
Shah SA, Khan M, Jo MH, Jo MG, Amin FU, Kim MO. Melatonin stimulates the SIRT1/Nrf2 signaling pathway counteracting lipopolysaccharide (LPS)-induced oxidative stress to rescue postnatal rat brain. CNS Neurosci Ther 2017; 23(1): 33-44.
[http://dx.doi.org/10.1111/cns.12588] [PMID: 27421686]
[71]
Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004; 23(12): 2369-80.
[http://dx.doi.org/10.1038/sj.emboj.7600244] [PMID: 15152190]
[72]
Salminen A, Kaarniranta K, Kauppinen A. Crosstalk between oxidative stress and SIRT1: Impact on the aging process. Int J Mol Sci 2013; 14(2): 3834-59.
[http://dx.doi.org/10.3390/ijms14023834] [PMID: 23434668]

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