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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

Author(s): Dubravka S. Strac*, Marcela Konjevod, Matea N. Perkovic, Lucija Tudor, Gordana N. Erjavec and Nela Pivac*

Volume 17, Issue 2, 2020

Page: [141 - 157] Pages: 17

DOI: 10.2174/1567205017666200317092310

Price: $65

Abstract

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease.

Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease.

Methods: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles.

Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications.

Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

Keywords: Dehydroepiandrosterone, dehydroepiandrosterone sulphate, Alzheimer’s disease, in vitro studies, animal models, patients, treatment.

[1]
Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement 14: 367-429. (2018).
[http://dx.doi.org/10.1016/j.jalz.2018.02.001]
[2]
Eid A, Mhatre I, Richardson JR. Gene-environment interactions in Alzheimer’s disease: A potential path to precision medicine. Pharmacol Ther 199: 173-87. (2019).
[http://dx.doi.org/10.1016/j.pharmthera.2019.03.005] [PMID: 30877021]
[3]
Gao Y, Tan L, Yu JT, Tan L. Tau in Alzheimer’s disease: mech-anisms and therapeutic strategies. Curr Alzheimer Res 15(3): 283-300. (2018).
[http://dx.doi.org/10.2174/1567205014666170417111859] [PMID: 28413986]
[4]
Reiss AB, Arain HA, Stecker MM, Siegart NM, Kasselman LJ. Amyloid toxicity in Alzheimer’s disease. Rev Neurosci 29(6): 613-27. (2018).
[http://dx.doi.org/10.1515/revneuro-2017-0063] [PMID: 29447116]
[5]
Scheff SW, Price DA. Alzheimer’s disease-related alterations in synaptic density: neocortex and hippocampus. J Alzheimers Dis 9(3): 101-15. (2006).
[http://dx.doi.org/10.3233/JAD-2006-9S312] [PMID: 16914849]
[6]
De Felice FG, Ferreira ST. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease. Diabetes 63(7): 2262-72. (2014).
[http://dx.doi.org/10.2337/db13-1954] [PMID: 24931033]
[7]
Yiannopoulou KG, Anastasiou AI, Zachariou V, Pelidou SH. Reasons for failed trials of disease-modifying treatments for Alzheimer disease and their contribution in recent research. Biomedicines 7(4)E97 (2019).
[http://dx.doi.org/10.3390/biomedicines7040097] [PMID: 31835422]
[8]
Wolkowitz OM, Reus VI. Neuropsychiatric effects of DHEA Dehydroepiandrosterone biochemical, physiological and clinical aspects. Berlin: De Gruyter 2000; pp. 272-3.
[http://dx.doi.org/10.1515/9783110811162.271]
[9]
Wolf OT, Kirschbaum C. Actions of dehydroepiandrosterone and its sulfate in the central nervous system: effects on cognition and emotion in animals and humans. Brain Res Brain Res Rev 30(3): 264-88. (1999).
[http://dx.doi.org/10.1016/S0165-0173(99)00021-1] [PMID: 10567728]
[10]
Labrie F, Luu-The V, Bélanger A, et al. Is dehydroepiandrosterone a hormone? J Endocrinol 187(2): 169-96. (2005).
[http://dx.doi.org/10.1677/joe.1.06264] [PMID: 16293766]
[11]
Auchus RJ. Overview of dehydroepiandrosterone biosynthesis. Semin Reprod Med 22(4): 281-8. (2004).
[http://dx.doi.org/10.1055/s-2004-861545] [PMID: 15635496]
[12]
Yen SS. Dehydroepiandrosterone sulfate and longevity: new clues for an old friend. Proc Natl Acad Sci USA 98(15): 8167-9. (2001).
[http://dx.doi.org/10.1073/pnas.161278698] [PMID: 11459947]
[13]
Klinge CM, Clark BJ, Prough RA. Dehydroepiandrosterone research: past, current, and future. Vitam Horm 108: 1-28. (2018).
[http://dx.doi.org/10.1016/bs.vh.2018.02.002] [PMID: 30029723]
[14]
Rainey WE, Carr BR, Sasano H, Suzuki T, Mason JI. Dissecting human adrenal androgen production. Trends Endocrinol Metab 13(6): 234-9. (2002).
[http://dx.doi.org/10.1016/S1043-2760(02)00609-4] [PMID: 12128283]
[15]
Mellon SH, Griffin LD. Neurosteroids: biochemistry and clinical significance. Trends Endocrinol Metab 13(1): 35-43. (2002).
[http://dx.doi.org/10.1016/S1043-2760(01)00503-3] [PMID: 11750861]
[16]
Baulieu EE, Robel P. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as neuroactive neurosteroids. Proc Natl Acad Sci USA 95(8): 4089-91. (1998).
[http://dx.doi.org/10.1073/pnas.95.8.4089] [PMID: 9539693]
[17]
Friess E, Schiffelholz T, Steckler T, Steiger A. Dehydroepiandrosterone--a neurosteroid. Eur J Clin Invest 30(3): 46-50. (2000).
[http://dx.doi.org/10.1046/j.1365-2362.2000.0300s3046.x] [PMID: 11281367]
[18]
Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA. The regulation of steroid action by sulfation and desulfation. Endocr Rev 36(5): 526-63. (2015).
[http://dx.doi.org/10.1210/er.2015-1036] [PMID: 26213785]
[19]
Tannenbaum C, Barrett-Connor E, Laughlin GA, Platt RW. A longitudinal study of dehydroepiandrosterone sulphate (DHEAS) change in older men and women: the Rancho Bernardo Study. Eur J Endocrinol 151(6): 717-25. (2004).
[http://dx.doi.org/10.1530/eje.0.1510717] [PMID: 15588238]
[20]
Auchus RJ, Rainey WE. Adrenarche - physiology, biochemistry and human disease. Clin Endocrinol (Oxf) 60(3): 288-96. (2004).
[http://dx.doi.org/10.1046/j.1365-2265.2003.01858.x] [PMID: 15008992]
[21]
Berr C, Lafont S, Debuire B, Dartigues JF, Baulieu EE. Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: a French community-based study. Proc Natl Acad Sci USA 93(23): 13410-5. (1996).
[http://dx.doi.org/10.1073/pnas.93.23.13410] [PMID: 8917605]
[22]
Sorwell KG, Urbanski HF. Dehydroepiandrosterone and age-related cognitive decline. Age (Dordr) 32(1): 61-7. (2010).
[http://dx.doi.org/10.1007/s11357-009-9113-4] [PMID: 19711196]
[23]
Schumacher M, Weill-Engerer S, Liere P, et al. Steroid hormones and neurosteroids in normal and pathological aging of the nervous system. Prog Neurobiol 71(1): 3-29. (2003).
[http://dx.doi.org/10.1016/j.pneurobio.2003.09.004] [PMID: 14611864]
[24]
Oberbeck R, Kobbe P. Dehydroepiandrosterone (DHEA): a steroid with multiple effects. Is there any possible option in the treatment of critical illness? Curr Med Chem 17(11): 1039-47. (2010).
[http://dx.doi.org/10.2174/092986710790820570] [PMID: 20156161]
[25]
Leowattana W. DHEA(S): the fountain of youth. J Med Assoc Thai 84(2): S605-12. (2001).
[PMID: 11853289]
[26]
Weng J-H, Chung BC. Nongenomic actions of neurosteroid pregnenolone and its metabolites. Steroids 111: 54-9. (2016).
[http://dx.doi.org/10.1016/j.steroids.2016.01.017] [PMID: 26844377]
[27]
Maninger N, Wolkowitz OM, Reus VI, Epel ES, Mellon SH. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Front Neuroendocrinol 30(1): 65-91. (2009).
[http://dx.doi.org/10.1016/j.yfrne.2008.11.002] [PMID: 19063914]
[28]
Traish AM, Kang HP, Saad F, Guay AT. Dehydroepiandrosterone (DHEA)--a precursor steroid or an active hormone in human physiology. J Sex Med 8(11): 2960-82. (2011).
[http://dx.doi.org/10.1111/j.1743-6109.2011.02523.x] [PMID: 22032408]
[29]
Webb SJ, Geoghegan TE, Prough RA, Michael Miller KK. The biological actions of dehydroepiandrosterone involves multiple receptors. Drug Metab Rev 38(1-2): 89-116. (2006).
[http://dx.doi.org/10.1080/03602530600569877] [PMID: 16684650]
[30]
Prough RA, Clark BJ, Klinge CM. Novel mechanisms for DHEA action. J Mol Endocrinol 56(3): R139-55. (2016).
[http://dx.doi.org/10.1530/JME-16-0013] [PMID: 26908835]
[31]
Widstrom RL, Dillon JS. Is there a receptor for dehydroepiandrosterone or dehydroepiandrosterone sulfate? Semin Reprod Med 22(4): 289-98. (2004).
[http://dx.doi.org/10.1055/s-2004-861546] [PMID: 15635497]
[32]
Lindschau C, Kirsch T, Klinge U, Kolkhof P, Peters I, Fiebeler A. Dehydroepiandrosterone-induced phosphorylation and translocation of FoxO1 depend on the mineralocorticoid receptor. Hypertension 58(3): 471-8. (2011).
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.171280] [PMID: 21747041]
[33]
Mo Q, Lu S, Garippa C, Brownstein MJ, Simon NG. Genome-wide analysis of DHEA- and DHT-induced gene expression in mouse hypothalamus and hippocampus. J Steroid Biochem Mol Biol 114(3-5): 135-43. (2009).
[http://dx.doi.org/10.1016/j.jsbmb.2009.01.015] [PMID: 19429443]
[34]
Liu D, Dillon JS. Dehydroepiandrosterone activates endothelial cell nitric-oxide synthase by a specific plasma membrane receptor coupled to Galpha(i2,3). J Biol Chem 277(24): 21379-88. (2002).
[http://dx.doi.org/10.1074/jbc.M200491200] [PMID: 11934890]
[35]
Charalampopoulos I, Alexaki VI, Lazaridis I, et al. G protein-associated, specific membrane binding sites mediate the neuroprotective effect of dehydroepiandrosterone. FASEB J 20(3): 577-9. (2006).
[http://dx.doi.org/10.1096/fj.05-5078fje] [PMID: 16407456]
[36]
Teng Y, Litchfield LM, Ivanova MM, Prough RA, Clark BJ, Klinge CM. Dehydroepiandrosterone-induces miR-21 transcription in HepG2 cells through estrogen receptor β and androgen receptor. Mol Cell Endocrinol 392(1-2): 23-36. (2014).
[http://dx.doi.org/10.1016/j.mce.2014.05.007] [PMID: 24845419]
[37]
Liang X, Glowacki J, Hahne J, Xie L, LeBoff MS, Zhou S. Dehydroepiandrosterone stimulation of osteoblastogenesis in human MSCs requires IGF-I signaling. J Cell Biochem 117(8): 1769-74. (2016).
[http://dx.doi.org/10.1002/jcb.25475] [PMID: 26682953]
[38]
Yoon SY, Roh DH, Seo HS, et al. Intrathecal injection of the neurosteroid, DHEAS, produces mechanical allodynia in mice: involvement of spinal sigma-1 and GABA receptors. Br J Pharmacol 157(4): 666-73. (2009).
[http://dx.doi.org/10.1111/j.1476-5381.2009.00197.x] [PMID: 19422393]
[39]
Johansson T, Elfverson M, Zhou Q, Nyberg F. Allosteric modulation of the NMDA receptor by neurosteroids in rat brain and the impact of long term morphine administration. Biochem Biophys Res Commun 401(4): 504-8. (2010).
[http://dx.doi.org/10.1016/j.bbrc.2010.09.073] [PMID: 20869946]
[40]
Bergeron R, de Montigny C, Debonnel G. Potentiation of neuronal NMDA response induced by dehydroepiandrosterone and its suppression by progesterone: effects mediated via sigma receptors. J Neurosci 16(3): 1193-202. (1996).
[http://dx.doi.org/10.1523/JNEUROSCI.16-03-01193.1996] [PMID: 8558248]
[41]
Maurice T, Phan VL, Urani A, Guillemain I. Differential involvement of the sigma(1) (sigma(1)) receptor in the anti-amnesic effect of neuroactive steroids, as demonstrated using an in vivo antisense strategy in the mouse. Br J Pharmacol 134(8): 1731-41. (2001).
[http://dx.doi.org/10.1038/sj.bjp.0704355] [PMID: 11739250]
[42]
Kokona D, Charalampopoulos I, Pediaditakis I, Gravanis A, Thermos K. The neurosteroid dehydroepiandrosterone (DHEA) protects the retina from AMPA-induced excitotoxicity: NGF TrkA receptor involvement. Neuropharmacology 62(5-6): 2106-17. (2012).
[http://dx.doi.org/10.1016/j.neuropharm.2012.01.006] [PMID: 22269901]
[43]
Pérez-Neri I, Montes S, Ojeda-López C, Ramírez-Bermúdez J, Ríos C. Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: mechanism of action and relevance to psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 32(5): 1118-30. (2008).
[http://dx.doi.org/10.1016/j.pnpbp.2007.12.001] [PMID: 18280022]
[44]
Demirgören S, Majewska MD, Spivak CE, London ED. Receptor binding and electrophysiological effects of dehydroepiandrosterone sulfate, an antagonist of the GABAA receptor. Neuroscience 45(1): 127-35. (1991).
[http://dx.doi.org/10.1016/0306-4522(91)90109-2] [PMID: 1661387]
[45]
Svob Štrac D, Jazvinšćak Jembrek M, Erhardt J, Mirković Kos K, Peričić D. Modulation of recombinant GABA(A) receptors by neurosteroid dehydroepiandrosterone sulfate. Pharmacology 89(3-4): 163-71. (2012).
[http://dx.doi.org/10.1159/000336058] [PMID: 22433179]
[46]
Park-Chung M, Malayev A, Purdy RH, Gibbs TT, Farb DH. Sulfated and unsulfated steroids modulate γ-aminobutyric acidA receptor function through distinct sites. Brain Res 830(1): 72-87. (1999).
[http://dx.doi.org/10.1016/S0006-8993(99)01381-5] [PMID: 10350561]
[47]
Pérez-Neri I, Méndez-Sánchez I, Montes S, Ríos C. Acute dehydroepiandrosterone treatment exerts different effects on dopamine and serotonin turnover ratios in the rat corpus striatum and nucleus accumbens. Prog Neuropsychopharmacol Biol Psychiatry 32(6): 1584-9. (2008).
[http://dx.doi.org/10.1016/j.pnpbp.2008.06.002] [PMID: 18585426]
[48]
Monnet FP, Mahé V, Robel P, Baulieu EE. Neurosteroids, via sigma receptors, modulate the [3H]norepinephrine release evoked by N-methyl-D-aspartate in the rat hippocampus. Proc Natl Acad Sci USA 92(9): 3774-8. (1995).
[http://dx.doi.org/10.1073/pnas.92.9.3774] [PMID: 7731982]
[49]
Laurine E, Lafitte D, Grégoire C, et al. Specific binding of dehydroepiandrosterone to the N terminus of the microtubule-associated protein MAP2. J Biol Chem 278(32): 29979-86. (2003).
[http://dx.doi.org/10.1074/jbc.M303242200] [PMID: 12775713]
[50]
Charalampopoulos I, Margioris AN, Gravanis A. Neurosteroid dehydroepiandrosterone exerts anti-apoptotic effects by membrane-mediated, integrated genomic and non-genomic pro-survival signaling pathways. J Neurochem 107(5): 1457-69. (2008).
[http://dx.doi.org/10.1111/j.1471-4159.2008.05732.x] [PMID: 19013851]
[51]
Lazaridis I, Charalampopoulos I, Alexaki VI, et al. Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis. PLoS Biol 9(4)e1001051 (2011).
[http://dx.doi.org/10.1371/journal.pbio.1001051] [PMID: 21541365]
[52]
Chakraborti A, Gulati K, Ray A. Involvement of nitric oxide in the protective effects of dehydroepiandrosterone sulphate on stress induced neurobehavioral suppression and brain oxidative injury in rats. Eur J Pharmacol 652(1-3): 55-9. (2011).
[http://dx.doi.org/10.1016/j.ejphar.2010.11.002] [PMID: 21114993]
[53]
Chevalier M, Gilbert G, Lory P, Marthan R, Quignard JF, Savineau JP. Dehydroepiandrosterone (DHEA) inhibits voltage-gated T-type calcium channels. Biochem Pharmacol 83(11): 1530-9. (2012).
[http://dx.doi.org/10.1016/j.bcp.2012.02.025] [PMID: 22391268]
[54]
Grimm A, Schmitt K, Lang UE, Mensah-Nyagan AG, Eckert A. Dehydroepiandrosterone sulfate, cholesterol, hemoglobin, and anthropometric measures related to growth in male adolescents. J Am Diet Assoc 91: 575-9. (2014).
[55]
Chen CC, Parker CR Jr. Adrenal androgens and the immune system. Semin Reprod Med 22(4): 369-77. (2004).
[http://dx.doi.org/10.1055/s-2004-861553] [PMID: 15635504]
[56]
Arquitt AB, Stoecker BJ, Hermann JS, Winterfeldt EA. Dehydroepiandrosterone sulfate, cholesterol, hemoglobin, and anthropometric measures related to growth in male adolescents. J Am Diet Assoc 91(5): 575-9. (1991).
[PMID: 1826915]
[57]
Nawata H, Yanase T, Goto K, Okabe T, Ashida K. Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S. Mech Ageing Dev 123(8): 1101-6. (2002).
[http://dx.doi.org/10.1016/S0047-6374(01)00393-1] [PMID: 12044959]
[58]
Leowattana W. DHEAS as a new diagnostic tool. Clin Chim Acta 341(1-2): 1-15. (2004).
[http://dx.doi.org/10.1016/j.cccn.2003.10.031] [PMID: 14967152]
[59]
Zhang L, Li Bs, Ma W, et al. Dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) regulate apoptosis during neurogenesis by triggering the Akt signaling pathway in opposing ways. Brain Res Mol Brain Res 98(1-2): 58-66. (2002).
[http://dx.doi.org/10.1016/S0169-328X(01)00315-1] [PMID: 11834296]
[60]
Kurata K, Takebayashi M, Morinobu S, Yamawaki S. beta-estradiol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate protect against N-methyl-D-aspartate-induced neurotoxicity in rat hippocampal neurons by different mechanisms. J Pharmacol Exp Ther 311(1): 237-45. (2004).
[http://dx.doi.org/10.1124/jpet.104.067629] [PMID: 15175425]
[61]
Taylor MK, Stone M, Laurent HK, Rauh MJ, Granger DA. Neuroprotective-neurotrophic effect of endogenous dehydroepiandrosterone sulfate during intense stress exposure. Steroids 87: 54-8. (2014).
[http://dx.doi.org/10.1016/j.steroids.2014.05.011] [PMID: 24887210]
[62]
Mellon SH. Neurosteroid regulation of central nervous system development. Pharmacol Ther 116(1): 107-24. (2007).
[http://dx.doi.org/10.1016/j.pharmthera.2007.04.011] [PMID: 17651807]
[63]
Kaasik A, Kalda A, Jaako K, Zharkovsky A. Dehydroepiandrosterone sulphate prevents oxygen-glucose deprivation-induced injury in cerebellar granule cell culture. Neuroscience 102(2): 427-32. (2001).
[http://dx.doi.org/10.1016/S0306-4522(00)00489-9] [PMID: 11166128]
[64]
Li H, Klein G, Sun P, Buchan AM. Dehydroepiandrosterone (DHEA) reduces neuronal injury in a rat model of global cerebral ischemia. Brain Res 888(2): 263-6. (2001).
[http://dx.doi.org/10.1016/S0006-8993(00)03077-8] [PMID: 11150483]
[65]
Fiore C, Inman DM, Hirose S, Noble LJ, Igarashi T, Compagnone NA. Treatment with the neurosteroid dehydroepiandrosterone promotes recovery of motor behavior after moderate contusive spinal cord injury in the mouse. J Neurosci Res 75(3): 391-400. (2004).
[http://dx.doi.org/10.1002/jnr.10821] [PMID: 14743452]
[66]
Iwasaki Y, Asai M, Yoshida M, Nigawara T, Kambayashi M, Nakashima N. Dehydroepiandrosterone-sulfate inhibits nuclear factor-kappaB-dependent transcription in hepatocytes, possibly through antioxidant effect. J Clin Endocrinol Metab 89(7): 3449-54. (2004).
[http://dx.doi.org/10.1210/jc.2003-031441] [PMID: 15240630]
[67]
Fedotova J, Sapronov N. Behavioral effects of dehydroepiandrosterone in adult male rats. Prog Neuropsychopharmacol Biol Psychiatry 28(6): 1023-7. (2004).
[http://dx.doi.org/10.1016/j.pnpbp.2004.05.037] [PMID: 15380863]
[68]
Maayan R, Touati-Werner D, Ram E, Strous R, Keren O, Weizman A. The protective effect of frontal cortex dehydroepiandrosterone in anxiety and depressive models in mice. Pharmacol Biochem Behav 85(2): 415-21. (2006).
[http://dx.doi.org/10.1016/j.pbb.2006.09.010] [PMID: 17109944]
[69]
Nicolas LB, Pinoteau W, Papot S, Routier S, Guillaumet G, Mortaud S. Aggressive behavior induced by the steroid sulfatase inhibitor COUMATE and by DHEAS in CBA/H mice. Brain Res 922(2): 216-22. (2001).
[http://dx.doi.org/10.1016/S0006-8993(01)03171-7] [PMID: 11743952]
[70]
Milman A, Zohar O, Maayan R, Weizman R, Pick CG. DHEAS repeated treatment improves cognitive and behavioral deficits after mild traumatic brain injury. Eur Neuropsychopharmacol 18(3): 181-7. (2008).
[http://dx.doi.org/10.1016/j.euroneuro.2007.05.007] [PMID: 17669633]
[71]
de Bruin VM, Vieira MC, Rocha MN, Viana GS. Cortisol and dehydroepiandosterone sulfate plasma levels and their relationship to aging, cognitive function, and dementia. Brain Cogn 50(2): 316-23. (2002).
[http://dx.doi.org/10.1016/S0278-2626(02)00519-5] [PMID: 12464198]
[72]
Ben Dor R, Marx CE, Shampine LJ, Rubinow DR, Schmidt PJ. DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA’s antidepressant action. Psychopharmacology (Berl) 232(18): 3375-83. (2015).
[http://dx.doi.org/10.1007/s00213-015-3991-1] [PMID: 26105109]
[73]
Söndergaard HP, Hansson LO, Theorell T. Elevated blood levels of dehydroepiandrosterone sulphate vary with symptom load in posttraumatic stress disorder: findings from a longitudinal study of refugees in Sweden. Psychother Psychosom 71(5): 298-303. (2002).
[http://dx.doi.org/10.1159/000064806] [PMID: 12207110]
[74]
Strous RD, Maayan R, Lapidus R, et al. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry 60(2): 133-41. (2003).
[http://dx.doi.org/10.1001/archpsyc.60.2.133] [PMID: 12578430]
[75]
Hillen T, Lun A, Reischies FM, Borchelt M, Steinhagen-Thiessen E, Schaub RT. DHEA-S plasma levels and incidence of Alzheimer’s disease. Biol Psychiatry 47(2): 161-3. (2000).
[http://dx.doi.org/10.1016/S0006-3223(99)00217-6] [PMID: 10664834]
[76]
Orentreich N, Brind JL, Vogelman JH, Andres R, Baldwin H. Long-term longitudinal measurements of plasma dehydroepiandrosterone sulfate in normal men. J Clin Endocrinol Metab 75(4): 1002-4. (1992).
[PMID: 1400863]
[77]
van Niekerk JK, Huppert FA, Herbert J. Salivary cortisol and DHEA: association with measures of cognition and well-being in normal older men, and effects of three months of DHEA supplementation. Psychoneuroendocrinology 26(6): 591-612. (2001).
[http://dx.doi.org/10.1016/S0306-4530(01)00014-2] [PMID: 11403980]
[78]
Haden ST, Glowacki J, Hurwitz S, Rosen C, LeBoff MS. Effects of age on serum dehydroepiandrosterone sulfate, IGF-I, and IL-6 levels in women. Calcif Tissue Int 66(6): 414-8. (2000).
[http://dx.doi.org/10.1007/s002230010084] [PMID: 10821876]
[79]
Murialdo G, Barreca A, Nobili F, et al. Relationships between cortisol, dehydroepiandrosterone sulphate and insulin-like growth factor-I system in dementia. J Endocrinol Invest 24(3): 139-46. (2001).
[http://dx.doi.org/10.1007/BF03343833]
[80]
Chung HY, Cesari M, Anton S, et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 8(1): 18-30. (2009).
[http://dx.doi.org/10.1016/j.arr.2008.07.002] [PMID: 18692159]
[81]
Dillon JS. Dehydroepiandrosterone, dehydroepiandrosterone sulfate and related steroids: their role in inflammatory, allergic and immunological disorders. Curr Drug Targets Inflamm Allergy 4(3): 377-85. (2005).
[http://dx.doi.org/10.2174/1568010054022079] [PMID: 16101547]
[82]
Haffner SM, Valdez RA, Mykkänen L, Stern MP, Katz MS. Decreased testosterone and dehydroepiandrosterone sulfate concentrations are associated with increased insulin and glucose concentrations in nondiabetic men. Metabolism 43(5): 599-603. (1994).
[http://dx.doi.org/10.1016/0026-0495(94)90202-X] [PMID: 8177048]
[83]
Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes--systematic overview of prospective observational studies. Diabetologia 48(12): 2460-9. (2005).
[http://dx.doi.org/10.1007/s00125-005-0023-4] [PMID: 16283246]
[84]
Luchsinger JA, Tang MX, Shea S, Mayeux R. Hyperinsulinemia and risk of Alzheimer disease. Neurology 63(7): 1187-92. (2004).
[http://dx.doi.org/10.1212/01.WNL.0000140292.04932.87] [PMID: 15477536]
[85]
Chen CY, Wu CC, Huang YC, Hung CF, Wang LJ. Gender differences in the relationships among neurosteroid serum levels, cognitive function, and quality of life. Neuropsychiatr Dis Treat 14: 2389-99. (2018).
[http://dx.doi.org/10.2147/NDT.S176047] [PMID: 30275693]
[86]
Racchi M, Govoni S, Solerte SB, Galli CL, Corsini E. Dehydroepiandrosterone and the relationship with aging and memory: a possible link with protein kinase C functional machinery. Brain Res Brain Res Rev 37(1-3): 287-93. (2001).
[http://dx.doi.org/10.1016/S0165-0173(01)00132-1] [PMID: 11744093]
[87]
Battaini F, Elkabes S, Bergamaschi S, et al. Protein kinase C activity, translocation, and conventional isoforms in aging rat brain. Neurobiol Aging 16(2): 137-48. (1995).
[http://dx.doi.org/10.1016/0197-4580(94)00154-5] [PMID: 7777132]
[88]
Battaini F, Pascale A, Lucchi L, Pasinetti GM, Govoni S. Protein kinase C anchoring deficit in postmortem brains of Alzheimer’s disease patients. Exp Neurol 159(2): 559-64. (1999).
[http://dx.doi.org/10.1006/exnr.1999.7151] [PMID: 10506528]
[89]
Yanase T, Fukahori M, Taniguchi S, et al. Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in Alzheimer’s disease and in cerebrovascular dementia. Endocr J 43(1): 119-23. (1996).
[http://dx.doi.org/10.1507/endocrj.43.119] [PMID: 8732462]
[90]
Morrison MF, Redei E, TenHave T, et al. Dehydroepiandrosterone sulfate and psychiatric measures in a frail, elderly residential care population. Biol Psychiatry 47(2): 144-50. (2000).
[http://dx.doi.org/10.1016/S0006-3223(99)00099-2] [PMID: 10664831]
[91]
Maggio M, De Vita F, Fisichella A, et al. DHEA and cognitive function in the elderly. J Steroid Biochem Mol Biol 145: 281-92. (2015).
[http://dx.doi.org/10.1016/j.jsbmb.2014.03.014] [PMID: 24794824]
[92]
Moffat SD, Zonderman AB, Harman SM, Blackman MR, Kawas C, Resnick SM. The relationship between longitudinal declines in dehydroepiandrosterone sulfate concentrations and cognitive performance in older men. Arch Intern Med 160(14): 2193-8. (2000).
[http://dx.doi.org/10.1001/archinte.160.14.2193] [PMID: 10904463]
[93]
Grimley Evans J, Malouf R, Huppert F, van Niekerk JK. Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst Rev (4): CD006221 (2006).
[http://dx.doi.org/10.1002/14651858.CD006221] [PMID: 17054283]
[94]
Brown RC, Han Z, Cascio C, Papadopoulos V. Oxidative stress-mediated DHEA formation in Alzheimer’s disease pathology. Neurobiol Aging 24(1): 57-65. (2003).
[http://dx.doi.org/10.1016/S0197-4580(02)00048-9] [PMID: 12493551]
[95]
Rammouz G, Lecanu L, Papadopoulos V. Oxidative stress-mediated brain dehydroepiandrosterone (DHEA) formation in Alzheimer’s disease diagnosis. Front Endocrinol (Lausanne) 2: 69. (2011).
[http://dx.doi.org/10.3389/fendo.2011.00069] [PMID: 22654823]
[96]
Naylor JC, Hulette CM, Steffens DC, et al. Cerebrospinal fluid dehydroepiandrosterone levels are correlated with brain dehydroepiandrosterone levels, elevated in Alzheimer’s disease, and related to neuropathological disease stage. J Clin Endocrinol Metab 93(8): 3173-8. (2008).
[http://dx.doi.org/10.1210/jc.2007-1229] [PMID: 18477662]
[97]
Weill-Engerer S, David JP, Sazdovitch V, et al. Neurosteroid quantification in human brain regions: comparison between Alzheimer’s and nondemented patients. J Clin Endocrinol Metab 87(11): 5138-43. (2002).
[http://dx.doi.org/10.1210/jc.2002-020878] [PMID: 12414884]
[98]
Ray L, Khemka VK, Behera P, et al. Serum homocysteine, dehydroepiandrosterone sulphate and lipoprotein (a) in Alzheimer’s disease and vascular dementia. Aging Dis 4(2): 57-64. (2013).
[PMID: 23696950]
[99]
Pan X, Wu X, Kaminga AC, Wen SW, Liu A. Dehydroepiandrosterone and dehydroepiandrosterone sulfate in Alzheimer’s disease: a systematic review and meta-analysis. Front Aging Neurosci 11: 61. (2019).
[http://dx.doi.org/10.3389/fnagi.2019.00061] [PMID: 30983988]
[100]
Gandy S. Neurohormonal signaling pathways and the regulation of Alzheimer β-amyloid precursor metabolism. Trends Endocrinol Metab 10(7): 273-9. (1999).
[http://dx.doi.org/10.1016/S1043-2760(99)00166-6] [PMID: 10461174]
[101]
Gandy S. Molecular basis for anti-amyloid therapy in the prevention and treatment of Alzheimer’s disease. Neurobiol Aging 23(6): 1009-16. (2002).
[http://dx.doi.org/10.1016/S0197-4580(02)00125-2] [PMID: 12470796]
[102]
Li L, Xu B, Zhu Y, Chen L, Sokabe M, Chen L. DHEA prevents Aβ25-35-impaired survival of newborn neurons in the dentate gyrus through a modulation of PI3K-Akt-mTOR signaling. Neuropharmacology 59(4-5): 323-33. (2010).
[http://dx.doi.org/10.1016/j.neuropharm.2010.02.009] [PMID: 20167228]
[103]
Kawahara M, Negishi-Kato M, Sadakane Y. Calcium dyshomeostasis and neurotoxicity of Alzheimer’s β-amyloid protein. Expert Rev Neurother 9(5): 681-93. (2009).
[http://dx.doi.org/10.1586/ern.09.28] [PMID: 19402778]
[104]
Dhatariya KK, Nair KS. Dehydroepiandrosterone: is there a role for replacement? Mayo Clin Proc 78(10): 1257-73. (2003).
[http://dx.doi.org/10.4065/78.10.1257] [PMID: 14531485]
[105]
Danenberg HD, Haring R, Fisher A, Pittel Z, Gurwitz D, Heldman E. Dehydroepiandrosterone (DHEA) increases production and release of Alzheimer’s amyloid precursor protein. Life Sci 59(19): 1651-7. (1996).
[http://dx.doi.org/10.1016/0024-3205(96)00496-1] [PMID: 8913330]
[106]
Buée L, Bussière T, Buée-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33(1): 95-130. (2000).
[http://dx.doi.org/10.1016/S0165-0173(00)00019-9] [PMID: 10967355]
[107]
Schaeffer V, Patte-Mensah C, Eckert A, Mensah-Nyagan AG. Modulation of neurosteroid production in human neuroblastoma cells by Alzheimer’s disease key proteins. J Neurobiol 66(8): 868-81. (2006).
[http://dx.doi.org/10.1002/neu.20267] [PMID: 16673391]
[108]
Lahmy V, Meunier J, Malmström S, et al. Blockade of Tau hyperphosphorylation and Aβ1−42 generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and σ1 receptor agonist, in a nontransgenic mouse model of Alzheimer’s disease. Neuropsychopharmacology 38(9): 1706-23. (2013).
[http://dx.doi.org/10.1038/npp.2013.70] [PMID: 23493042]
[109]
Grimm A, Biliouris EE, Lang UE, Götz J, Mensah-Nyagan AG, Eckert A. Sex hormone-related neurosteroids differentially rescue bioenergetic deficits induced by amyloid-β or hyperphosphorylated tau protein. Cell Mol Life Sci 73(1): 201-15. (2016).
[http://dx.doi.org/10.1007/s00018-015-1988-x] [PMID: 26198711]
[110]
Wojtal K, Trojnar MK, Czuczwar SJ. Endogenous neuroprotective factors: neurosteroids. Pharmacol Rep 58(3): 335-40. (2006).
[PMID: 16845207]
[111]
Grimm A, Lim Y-A, Mensah-Nyagan AG, Götz J, Eckert A. Alzheimer’s disease, oestrogen and mitochondria: an ambiguous relationship. Mol Neurobiol 46(1): 151-60. (2012).
[http://dx.doi.org/10.1007/s12035-012-8281-x] [PMID: 22678467]
[112]
Marchisella F, Coffey ET, Hollos P. Microtubule and microtubule associated protein anomalies in psychiatric disease. Cytoskeleton (Hoboken) 73(10): 596-611. (2016).
[http://dx.doi.org/10.1002/cm.21300] [PMID: 27112918]
[113]
Compagnone NA, Mellon SH. Dehydroepiandrosterone: a potential signalling molecule for neocortical organization during development. Proc Natl Acad Sci USA 95(8): 4678-83. (1998).
[http://dx.doi.org/10.1073/pnas.95.8.4678] [PMID: 9539798]
[114]
Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 66(2): 137-47. (1999).
[http://dx.doi.org/10.1136/jnnp.66.2.137] [PMID: 10071091]
[115]
Kása P, Rakonczay Z, Gulya K. The cholinergic system in Alzheimer’s disease. Prog Neurobiol 52(6): 511-35. (1997).
[http://dx.doi.org/10.1016/S0301-0082(97)00028-2] [PMID: 9316159]
[116]
George O, Vallée M, Le Moal M, Mayo W. Neurosteroids and cholinergic systems: implications for sleep and cognitive processes and potential role of age-related changes. Psychopharmacology (Berl) 186(3): 402-13. (2006).
[http://dx.doi.org/10.1007/s00213-005-0254-6] [PMID: 16416333]
[117]
Lawrence AD, Sahakian BJ. Alzheimer disease, attention, and the cholinergic system. Alzheimer Dis Assoc Disord 9(2): 43-9. (1995).
[http://dx.doi.org/10.1097/00002093-199501002-00008] [PMID: 8534423]
[118]
Shi J, Schulze S, Lardy HA. The effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice. Steroids 65(3): 124-9. (2000).
[http://dx.doi.org/10.1016/S0039-128X(99)00094-X] [PMID: 10699590]
[119]
Schverer M, Lanfumey L, Baulieu EE, Froger N, Villey I. Neurosteroids: non-genomic pathways in neuroplasticity and involvement in neurological diseases. Pharmacol Ther 191: 190-206. (2018).
[http://dx.doi.org/10.1016/j.pharmthera.2018.06.011] [PMID: 29953900]
[120]
Moriguchi S, Shinoda Y, Yamamoto Y, et al. Stimulation of the sigma-1 receptor by DHEA enhances synaptic efficacy and neurogenesis in the hippocampal dentate gyrus of olfactory bulbectomized mice. PLoS One 8(4)e60863 (2013).
[http://dx.doi.org/10.1371/journal.pone.0060863] [PMID: 23593332]
[121]
Hajszan T, MacLusky NJ, Leranth C. Dehydroepiandrosterone increases hippocampal spine synapse density in ovariectomized female rats. Endocrinology 145(3): 1042-5. (2004).
[http://dx.doi.org/10.1210/en.2003-1252] [PMID: 14645116]
[122]
Chen L, Miyamoto Y, Furuya K, Dai XN, Mori N, Sokabe M. Chronic DHEAS administration facilitates hippocampal long-term potentiation via an amplification of Src-dependent NMDA receptor signaling. Neuropharmacology 51(3): 659-70. (2006).
[http://dx.doi.org/10.1016/j.neuropharm.2006.05.011] [PMID: 16806295]
[123]
Xu Y, Tanaka M, Chen L, Sokabe M. DHEAS induces short-term potentiation via the activation of a metabotropic glutamate receptor in the rat hippocampus. Hippocampus 22(4): 707-22. (2012).
[http://dx.doi.org/10.1002/hipo.20932] [PMID: 21484933]
[124]
El Bitar F, Meunier J, Villard V, Almeras M, Krishnan K, Covey DF, et al. Neuroprotection by the synthetic neurosteroid enantiomers ent-PREGS and ent-DHEAS against Abeta(2)(5)(-)(3)(5) peptide-induced toxicity in vitro and in vivo in mice. Psychopharmacology 231: 3293-312. (2014).
[125]
Qaiser MZ, Dolman DEM, Begley DJ, et al. Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat. J Neurochem 142(5): 672-85. (2017).
[http://dx.doi.org/10.1111/jnc.14117] [PMID: 28665486]
[126]
Nedic Erjavec G, Konjevod M, Perkovic MN, et al. Short overview on metabolomic approach and redox changes in psychiatric disorders. Redox Biol 14: 178-86. (2018).
[http://dx.doi.org/10.1016/j.redox.2017.09.002] [PMID: 28942195]
[127]
Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. Clin Interv Aging 13: 757-72. (2018).
[http://dx.doi.org/10.2147/CIA.S158513] [PMID: 29731617]
[128]
Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J 5(1): 9-19. (2012).
[http://dx.doi.org/10.1097/WOX.0b013e3182439613] [PMID: 23268465]
[129]
Facecchia K, Fochesato LA, Ray SD, Stohs SJ, Pandey S. Oxidative toxicity in neurodegenerative diseases: role of mitochondrial dysfunction and therapeutic strategies. J Toxicol 2011683728 (2011).
[http://dx.doi.org/10.1155/2011/683728] [PMID: 21785590]
[130]
Rojo AI, McBean G, Cindric M, et al. Redox control of microglial function: molecular mechanisms and functional significance. Antioxid Redox Signal 21(12): 1766-801. (2014).
[http://dx.doi.org/10.1089/ars.2013.5745] [PMID: 24597893]
[131]
Cha MY, Han SH, Son SM, et al. Mitochondria-specific accumulation of amyloid β induces mitochondrial dysfunction leading to apoptotic cell death. PLoS One 7(4)e34929 (2012).
[http://dx.doi.org/10.1371/journal.pone.0034929] [PMID: 22514691]
[132]
Praticò D, Delanty N. Oxidative injury in diseases of the central nervous system: focus on Alzheimer’s disease. Am J Med 109(7): 577-85. (2000).
[http://dx.doi.org/10.1016/S0002-9343(00)00547-7] [PMID: 11063960]
[133]
Agostinho P, Cunha RA, Oliveira C. Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer’s disease. Curr Pharm Des 16(25): 2766-78. (2010).
[http://dx.doi.org/10.2174/138161210793176572] [PMID: 20698820]
[134]
Tönnies E, Trushina E. Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis 57(4): 1105-21. (2017).
[http://dx.doi.org/10.3233/JAD-161088] [PMID: 28059794]
[135]
Feng Y, Wang X. Antioxidant therapies for Alzheimer’s disease. Oxid Med Cell Longev 2012472932 (2012).
[http://dx.doi.org/10.1155/2012/472932] [PMID: 22888398]
[136]
Powrie YSL, Smith C. Central intracrine DHEA synthesis in ageing-related neuroinflammation and neurodegeneration: therapeutic potential? J Neuroinflammation 15(1): 289. (2018).
[http://dx.doi.org/10.1186/s12974-018-1324-0] [PMID: 30326923]
[137]
Tamagno E, Aragno M, Boccuzzi G, et al. Oxygen free radical scavenger properties of dehydroepiandrosterone. Cell Biochem Funct 16(1): 57-63. (1998).
[http://dx.doi.org/10.1002/(SICI)1099-0844(199803)16:1<57:AID-CBF771>3.0.CO;2-S] [PMID: 9519460]
[138]
Jacob MH, Janner DdaR, Belló-Klein A, Llesuy SF, Ribeiro MF. Dehydroepiandrosterone modulates antioxidant enzymes and Akt signaling in healthy Wistar rat hearts. J Steroid Biochem Mol Biol 112(1-3): 138-44. (2008).
[http://dx.doi.org/10.1016/j.jsbmb.2008.09.008] [PMID: 18848627]
[139]
Li L, Zhao J, Ge C, Yu L, Ma H. Dehydroepiandrosterone rehabilitate BRL-3A cells oxidative stress damage induced by hydrogen peroxide. J Cell Physiol 233(8): 6262-72. (2018).
[http://dx.doi.org/10.1002/jcp.26458] [PMID: 29521449]
[140]
Gallo M, Aragno M, Gatto V, et al. Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line. Eur J Endocrinol 141(1): 35-9. (1999).
[http://dx.doi.org/10.1530/eje.0.1410035] [PMID: 10407220]
[141]
Mastrocola R, Aragno M, Betteto S, et al. Pro-oxidant effect of dehydroepiandrosterone in rats is mediated by PPAR activation. Life Sci 73(3): 289-99. (2003).
[http://dx.doi.org/10.1016/S0024-3205(03)00287-X] [PMID: 12757836]
[142]
Schwartz AG, Pashko LL. Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and longevity. Ageing Res Rev 3(2): 171-87. (2004).
[http://dx.doi.org/10.1016/j.arr.2003.05.001] [PMID: 15177053]
[143]
Cheng ZX, Lan DM, Wu PY, et al. Neurosteroid dehydroepiandrosterone sulphate inhibits persistent sodium currents in rat medial prefrontal cortex via activation of sigma-1 receptors. Exp Neurol 210(1): 128-36. (2008).
[http://dx.doi.org/10.1016/j.expneurol.2007.10.004] [PMID: 18035354]
[144]
Görlach A, Bertram K, Hudecova S, Krizanova O. Calcium and ROS: A mutual interplay. Redox Biol 6: 260-71. (2015).
[http://dx.doi.org/10.1016/j.redox.2015.08.010] [PMID: 26296072]
[145]
Kipper-Galperin M, Galilly R, Danenberg HD, Brenner T. Dehydroepiandrosterone selectively inhibits production of tumor necrosis factor alpha and interleukin-6 [correction of interlukin-6] in astrocytes. Int J Dev Neurosci 17(8): 765-75. (1999).
[http://dx.doi.org/10.1016/S0736-5748(99)00067-2] [PMID: 10593612]
[146]
Vieira-Marques C, Arbo BD, Ruiz-Palmero I, et al. Dehydroepiandrosterone protects male and female hippocampal neurons and neuroblastoma cells from glucose deprivation. Brain Res 1644: 176-82. (2016).
[http://dx.doi.org/10.1016/j.brainres.2016.05.014] [PMID: 27174000]
[147]
Maurice T, Phan V, Sandillon F, Urani A. Differential effect of dehydroepiandrosterone and its steroid precursor pregnenolone against the behavioural deficits in CO-exposed mice. Eur J Pharmacol 390(1-2): 145-55. (2000).
[http://dx.doi.org/10.1016/S0014-2999(00)00015-7] [PMID: 10708718]
[148]
Yabuki Y, Shinoda Y, Izumi H, Ikuno T, Shioda N, Fukunaga K. Dehydroepiandrosterone administration improves memory deficits following transient brain ischemia through sigma-1 receptor stimulation. Brain Res 1622: 102-13. (2015).
[http://dx.doi.org/10.1016/j.brainres.2015.05.006] [PMID: 26119915]
[149]
Kumar P, Taha A, Sharma D, Kale RK, Baquer NZ. Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions. Biogerontology 9(4): 235-46. (2008).
[http://dx.doi.org/10.1007/s10522-008-9133-y] [PMID: 18307051]
[150]
Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 14(4): 388-405. (2015).
[http://dx.doi.org/10.1016/S1474-4422(15)70016-5] [PMID: 25792098]
[151]
Lai KSP, Liu CS, Rau A, et al. Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies. J Neurol Neurosurg Psychiatry 88(10): 876-82. (2017).
[http://dx.doi.org/10.1136/jnnp-2017-316201] [PMID: 28794151]
[152]
Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 3(10): 136. (2015).
[PMID: 26207229]
[153]
Italiani P, Puxeddu I, Napoletano S, et al. Circulating levels of IL-1 family cytokines and receptors in Alzheimer’s disease: new markers of disease progression? J Neuroinflammation 15(1): 342. (2018).
[http://dx.doi.org/10.1186/s12974-018-1376-1] [PMID: 30541566]
[154]
Prall SP, Larson EE, Muehlenbein MP. The role of dehydroepiandrosterone on functional innate immune responses to acute stress. Stress Health 33(5): 656-64. (2017).
[http://dx.doi.org/10.1002/smi.2752] [PMID: 28401652]
[155]
Prall SP, Muehlenbein MP. DHEA Modulates Immune Function: A Review of Evidence. Vitam Horm 108: 125-44. (2018).
[http://dx.doi.org/10.1016/bs.vh.2018.01.023] [PMID: 30029724]
[156]
Brown RC, Cascio C, Papadopoulos V. Pathways of neurosteroid biosynthesis in cell lines from human brain: regulation of dehydroepiandrosterone formation by oxidative stress and beta-amyloid peptide. J Neurochem 74(2): 847-59. (2000).
[http://dx.doi.org/10.1046/j.1471-4159.2000.740847.x] [PMID: 10646538]
[157]
Rammouz G, Lecanu L, Aisen P, Papadopoulos V. A lead study on oxidative stress-mediated dehydroepiandrosterone formation in serum: the biochemical basis for a diagnosis of Alzheimer’s disease. J Alzheimers Dis 24(2): 5-16. (2011).
[http://dx.doi.org/10.3233/JAD-2011-101941] [PMID: 21335661]
[158]
Hildreth KL, Gozansky WS, Jankowski CM, Grigsby J, Wolfe P, Kohrt WM. Association of serum dehydroepiandrosterone sulfate and cognition in older adults: sex steroid, inflammatory, and metabolic mechanisms. Neuropsychology 27(3): 356-63. (2013).
[http://dx.doi.org/10.1037/a0032230] [PMID: 23688217]
[159]
Du C, Khalil MW, Sriram S. Administration of dehydroepiandrosterone suppresses experimental allergic encephalomyelitis in SJL/J mice. J Immunol 167(12): 7094-101. (2001).
[http://dx.doi.org/10.4049/jimmunol.167.12.7094] [PMID: 11739531]
[160]
Meikle AW, Dorchuck RW, Araneo BA, et al. The presence of a dehydroepiandrosterone-specific receptor binding complex in murine T cells. J Steroid Biochem Mol Biol 42(3-4): 293-304. (1992).
[http://dx.doi.org/10.1016/0960-0760(92)90132-3] [PMID: 1351401]
[161]
McLachlan JA, Serkin CD, Bakouche O. Dehydroepiandrosterone modulation of lipopolysaccharide-stimulated monocyte cytotoxicity. J Immunol 156(1): 328-35. (1996).
[PMID: 8598481]
[162]
Suzuki T, Suzuki N, Daynes RA, Engleman EG. Dehydroepiandrosterone enhances IL2 production and cytotoxic effector function of human T cells. Clin Immunol Immunopathol 61(2 Pt 1): 202-11. (1991).
[http://dx.doi.org/10.1016/S0090-1229(05)80024-8] [PMID: 1833106]
[163]
Aly HF, Metwally FM, Ahmed HH. Neuroprotective effects of dehydroepiandrosterone (DHEA) in rat model of Alzheimer’s disease. Acta Biochim Pol 58(4): 513-20. (2011).
[http://dx.doi.org/10.18388/abp.2011_2218] [PMID: 22146133]
[164]
Loria RM. Immune up-regulation and tumor apoptosis by androstene steroids. Steroids 67(12): 953-66. (2002).
[http://dx.doi.org/10.1016/S0039-128X(02)00043-0] [PMID: 12398992]
[165]
Sawalha AH, Kovats S. Dehydroepiandrosterone in systemic lupus erythematosus. Curr Rheumatol Rep 10(4): 286-91. (2008).
[http://dx.doi.org/10.1007/s11926-008-0046-1] [PMID: 18662508]
[166]
Kamin HS, Kertes DA. Cortisol and DHEA in development and psychopathology. Horm Behav 89: 69-85. (2017).
[http://dx.doi.org/10.1016/j.yhbeh.2016.11.018] [PMID: 27979632]
[167]
McNelis JC, Manolopoulos KN, Gathercole LL, et al. Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte proliferation, differentiation, and glucose uptake. Am J Physiol Endocrinol Metab 305(9): E1134-44. (2013).
[http://dx.doi.org/10.1152/ajpendo.00314.2012] [PMID: 24022868]
[168]
Clark BJ, Prough RA, Klinge CM. Mechanisms of Action of Dehydroepiandrosterone. Vitam Horm 108: 29-73. (2018).
[http://dx.doi.org/10.1016/bs.vh.2018.02.003] [PMID: 30029731]
[169]
Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R. Diabetes mellitus and risk of Alzheimer’s disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol 154(7): 635-41. (2001).
[http://dx.doi.org/10.1093/aje/154.7.635] [PMID: 11581097]
[170]
Xu J, Begley P, Church SJ, et al. Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: metabolic basis for dementia. Sci Rep 6: 27524. (2016).
[http://dx.doi.org/10.1038/srep27524] [PMID: 27276998]
[171]
An Y, Varma VR, Varma S, et al. Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement 14(3): 318-29. (2018).
[http://dx.doi.org/10.1016/j.jalz.2017.09.011] [PMID: 29055815]
[172]
Hokama M, Oka S, Leon J, et al. Altered expression of diabetes-related genes in Alzheimer’s disease brains: the Hisayama study. Cereb Cortex 24(9): 2476-88. (2014).
[http://dx.doi.org/10.1093/cercor/bht101] [PMID: 23595620]
[173]
de la Monte SM. Type 3 diabetes is sporadic Alzheimer׳s disease: mini-review. Eur Neuropsychopharmacol 24(12): 1954-60. (2014).
[http://dx.doi.org/10.1016/j.euroneuro.2014.06.008] [PMID: 25088942]
[174]
Chen Z, Zhong C. Decoding Alzheimer’s disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. Prog Neurobiol 108: 21-43. (2013).
[http://dx.doi.org/10.1016/j.pneurobio.2013.06.004] [PMID: 23850509]
[175]
Brahimaj A, Muka T, Kavousi M, Laven JS, Dehghan A, Franco OH. Serum dehydroepiandrosterone levels are associated with lower risk of type 2 diabetes: the Rotterdam Study. Diabetologia 60(1): 98-106. (2017).
[http://dx.doi.org/10.1007/s00125-016-4136-8] [PMID: 27771738]
[176]
Dillon JS, Yaney GC, Zhou Y, et al. Dehydroepiandrosterone sulfate and beta-cell function: enhanced glucose-induced insulin secretion and altered gene expression in rodent pancreatic beta-cells. Diabetes 49(12): 2012-20. (2000).
[http://dx.doi.org/10.2337/diabetes.49.12.2012] [PMID: 11118002]
[177]
Aoki K, Saito T, Satoh S, et al. Dehydroepiandrosterone suppresses the elevated hepatic glucose-6-phosphatase and fructose-1,6-bisphosphatase activities in C57BL/Ksj-db/db mice: comparison with troglitazone. Diabetes 48(8): 1579-85. (1999).
[http://dx.doi.org/10.2337/diabetes.48.8.1579] [PMID: 10426376]
[178]
Aoki K, Kikuchi T, Mukasa K, et al. Dehydroepiandrosterone suppresses elevated hepatic glucose-6-phosphatase mRNA level in C57BL/KsJ-db/db mice: comparison with troglitazone. Endocr J 47(6): 799-804. (2000).
[http://dx.doi.org/10.1507/endocrj.47.799] [PMID: 11228057]
[179]
Aoki K, Taniguchi H, Ito Y, et al. Dehydroepiandrosterone decreases elevated hepatic glucose production in C57BL/KsJ-db/db mice. Life Sci 74(25): 3075-84. (2004).
[http://dx.doi.org/10.1016/j.lfs.2003.10.031] [PMID: 15081573]
[180]
Medina MC, Souza LC, Caperuto LC, et al. Dehydroepiandrosterone increases beta-cell mass and improves the glucose-induced insulin secretion by pancreatic islets from aged rats. FEBS Lett 580(1): 285-90. (2006).
[http://dx.doi.org/10.1016/j.febslet.2005.12.014] [PMID: 16376341]
[181]
Corona G, Rastrelli G, Giagulli VA, et al. Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials. J Clin Endocrinol Metab 98(9): 3615-26. (2013).
[http://dx.doi.org/10.1210/jc.2013-1358] [PMID: 23824417]
[182]
Elraiyah T, Sonbol MB, Wang Z, et al. Clinical review: The benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab 99(10): 3536-42. (2014).
[http://dx.doi.org/10.1210/jc.2014-2261] [PMID: 25279571]
[183]
Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA 292(18): 2243-8. (2004).
[http://dx.doi.org/10.1001/jama.292.18.2243] [PMID: 15536111]
[184]
Brignardello E, Runzo C, Aragno M, et al. Dehydroepiandrosterone administration counteracts oxidative imbalance and advanced glycation end product formation in type 2 diabetic patients. Diabetes Care 30(11): 2922-7. (2007).
[http://dx.doi.org/10.2337/dc07-1110] [PMID: 17704347]
[185]
Luppi C, Fioravanti M, Bertolini B, et al. Growth factors decrease in subjects with mild to moderate Alzheimer’s disease (AD): potential correction with dehydroepiandrosterone-sulphate (DHEAS). Arch Gerontol Geriatr 49(1): 173-84. (2009).
[http://dx.doi.org/10.1016/j.archger.2009.09.027] [PMID: 19836631]
[186]
Talbot K, Wang HY, Kazi H, et al. Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 122(4): 1316-38. (2012).
[http://dx.doi.org/10.1172/JCI59903] [PMID: 22476197]
[187]
Farr SA, Banks WA, Uezu K, Gaskin FS, Morley JE. DHEAS improves learning and memory in aged SAMP8 mice but not in diabetic mice. Life Sci 75(23): 2775-85. (2004).
[http://dx.doi.org/10.1016/j.lfs.2004.05.026] [PMID: 15464829]
[188]
Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M. Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 9(7): 702-16. (2010).
[http://dx.doi.org/10.1016/S1474-4422(10)70119-8] [PMID: 20610346]
[189]
Dayal M, Sammel MD, Zhao J, Hummel AC, Vandenbourne K, Barnhart KT. Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids. J Womens Health (Larchmt) 14(5): 391-400. (2005).
[http://dx.doi.org/10.1089/jwh.2005.14.391] [PMID: 15989411]
[190]
Wolf OT, Kudielka BM, Hellhammer DH, Hellhammer J, Kirschbaum C. Opposing effects of DHEA replacement in elderly subjects on declarative memory and attention after exposure to a laboratory stressor. Psychoneuroendocrinology 23(6): 617-29. (1998).
[http://dx.doi.org/10.1016/S0306-4530(98)00032-8] [PMID: 9802132]
[191]
Kritz-Silverstein D, von Mühlen D, Laughlin GA, Bettencourt R. Effects of dehydroepiandrosterone supplementation on cognitive function and quality of life: the DHEA and Well-Ness (DAWN) Trial. J Am Geriatr Soc 56(7): 1292-8. (2008).
[http://dx.doi.org/10.1111/j.1532-5415.2008.01768.x] [PMID: 18482290]
[192]
Wang X, Feero WG. Does dehydroepiandrosterone decrease the risk of progression of Alzheimer’s dementia. Evi-Based Prac 22(2): 26. (2019).
[http://dx.doi.org/10.1097/EBP.0000000000000162]
[193]
Wolkowitz OM, Kramer JH, Reus VI, et al. DHEA treatment of Alzheimer’s disease: a randomized, double-blind, placebo-controlled study. Neurology 60(7): 1071-6. (2003).
[http://dx.doi.org/10.1212/01.WNL.0000052994.54660.58] [PMID: 12682308]
[194]
Yamada S, Akishita M, Fukai S, et al. Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment. Geriatr Gerontol Int 10(4): 280-7. (2010).
[http://dx.doi.org/10.1111/j.1447-0594.2010.00625.x] [PMID: 20497239]
[195]
Knopman D, Henderson VW. DHEA for Alzheimer’s disease: a modest showing by a superhormone. Neurology 60(7): 1060-1. (2003).
[http://dx.doi.org/10.1212/01.WNL.0000059944.48810.3A] [PMID: 12682305]
[196]
Olech E, Merrill JT. DHEA supplementation: the claims in perspective. Cleve Clin J Med 72(11): 965-966, 968, 970-971 passim. (2005).
[http://dx.doi.org/10.3949/ccjm.72.11.965] [PMID: 16315437]

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