Neuroprotection with non-feminizing estrogen analogues: An overlooked possible therapeutic strategy

Hormones and Behavior

Volumn 63, Issue 2, 2013, Pages 278-283

  Simpkins, James W ^a   Richardson, Timothy E ^a   Yi, Kun Don ^a   Perez, Evelyn ^a   Covey, Douglas F ^b  

^a UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Estrogen receptors; Estrogens; Hormone therapy; Neuroprotection; Non feminizing estrogens; Stroke

Indexed keywords

17ALPHA ESTRADIOL; ESTRADIOL; ESTROGEN DERIVATIVE; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; G PROTEIN COUPLED RECEPTOR 30;

ANTIOXIDANT ACTIVITY; BINDING AFFINITY; BRAIN INFARCTION SIZE; BRAIN ISCHEMIA; CHEMICAL STRUCTURE; ENANTIOMER; FRIEDREICH ATAXIA; HORMONE RECEPTOR INTERACTION; HORMONE SUBSTITUTION; HUMAN; MIDDLE CEREBRAL ARTERY OCCLUSION; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; POSTMENOPAUSE; PRIORITY JOURNAL; REVIEW; SEX DIFFERENCE;

ANIMALS; CYTOPROTECTION; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; ESTRADIOL CONGENERS; FEMALE; FEMINIZATION; FRIEDREICH ATAXIA; HUMANS; MALE; MODELS, BIOLOGICAL; NEUROPROTECTIVE AGENTS;

EID: 84872847834     PISSN: 0018506X     EISSN: 10956867     Source Type: Journal    
DOI: 10.1016/j.yhbeh.2012.03.013     Document Type: Review

References (63)

1. Alkayed N.J., Harukuni I., Kimes A.S., London E.D., Traystman R.J., Hurn P.D. Gender-linked brain injury in experimental stroke. Stroke 1998, 29:159-165.
2. Behl C., Skutella T., Lezoualc'h F., Post A., Widmann M., Newton C.J., Holsboer F. Neuroprotection againstoxidative stress by estrogens: structure-activity relationship. Mol. Pharmacol. 1997, 51:535-541.
3. Bingham D., Macrae I.M., Carswell H.V. Detrimental effects of 17β-oestradiol after permanent middle cerebral artery occulsion. J. Cereb. Blood Flow Metab. 2005, 25:414-420.
4. Brinton R.D. Requirements of a brain selective estrogen: advances and remaining challenges for developing a NeuroSERM. J. Alzheimers Dis. 2004, 6:S27-S35.
5. Carswell H.V., Anderson N.H., Morton J.J., McCulloch J., Dominiczak A.F., Macrae I.M. Investigation of estrogen status and increased stroke sensitivity on cerebral blood flow after a focal ischemic insult. J. Cereb. Blood Flow Metab. 2000, 20:931-936.
6. Carswell H.V., Dominiczak A.F., Macrae I.M. Estrogen status affects sensitivity to focal cerebral ischemia in stroke-prone spontaneously hypertensive rats. Am. J. Physiol. Heart Circ. Physiol. 2000, 278:H290-H294.
7. Coker L.H., Hogan P.E., Bryan N.R., Kuller L.H., Margolis K.L., Bettermann K., Wallace R.B., Lao Z., Freeman R., Stefanick M.L., Shumaker S.A. Postmenopausal hormone therapy and subclinical cerebrovascular disease: the WHIMS-MRI Study. Neurology 2009, 72:125-134.
8. Dubal D.B., Wise P.M. Neuroprotective effects of estradiol in middle-aged female rats. Endocrinology 2001, 142:43-48.
9. Dubal D.B., Kashon M.L., Pettigrew L.C., Ren J.M., Finklestein S.P., Rau S.W., Wise P.M. Estradiol protects against ischemic injury. J. Cereb. Blood Flow Metab. 1998, 18:1253-1258.
10. Dubal D.B., Zhu H., Yu J., Rau S.W., Shughrue P.J., Merchenthaler I., Kindy M.S., Wise P.M. Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:1952-1957.
11. Dubey R.K., Imthurn B., Barton M., Jackson E.K. Vascular consequences of menopause and hormone therapy: importance of timing of treatment and type of estrogen. Cardiovasc. Res. 2005, 66:295-306.
12. Dumas J., Hancur-Bucci C., Naylor M., Sites C., Newhouse P. Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: evidence for the critical period hypothesis. Horm. Behav. 2008, 53:159-169.
13. Fan T., Perez E.J., Eberst K.L., Covey D.F., Chen H.X., Day A.L., Simpkins J.W. ZYC-13, the enantiomer of 1, 3, 5(10)-estratriene 3-ol, exerts neuroprotective effects in vitro and in vivo 2001, Society for Neuroscience, (Abstract A 27).
14. Finucane F.F., Madans J.H., Bush T.L., Wolf P.H., Kleinman J.C. Decreased risk of stroke among postmenopausal hormone users. Results from a national cohort. Arch. Intern. Med. 1993, 153:73-79.
15. Gelinas S., Martinoli M.G. Neuroprotective effect of estradiol and phytoestrogens on MPP+-induced cytotoxicity in neuronal PC12 cells. J. Neurosci. Res. 2002, 70:90-96.
16. Green P.S., Simpkins J.W. Neuroprotective effects of estrogens: potential mechanisms of action. Int. J. Dev. Neurosci. 2000, 18:347-358.
17. Green P.S., Gridley K.E., Simpkins J.W. Estradiol protects against beta-amyloid (25-35)-induced toxicity in SK-N-SH human neuroblastoma cells. Neurosci. Lett. 1996, 218:165-168.
18. Green P.S., Bishop J., Simpkins J.W. 17 alpha-estradiol exerts neuroprotective effects on SK-N-SH cells. J. Neurosci. 1997, 17:511-515.
19. Green P.S., Gordon K., Simpkins J.W. Phenolic A ring requirement for the neuroprotective effects of steroids. J. Steroid Biochem. Mol. Biol. 1997, 63:229-235.
20. Green P.S., Gridley K.E., Simpkins J.W. Nuclear estrogen receptor-independent neuroprotection by estratrienes: a novel interaction with glutathione. Neuroscience 1998, 84:7-10.
21. Green P.S., Yang S.H., Nilsson K.R., Kumar A.S., Covey D.F., Simpkins J.W. The nonfeminizing enantiomer of 17beta-estradiol exerts protective effects in neuronal cultures and a rat model of cerebral ischemia. Endocrinology 2001, 142:400-406.
22. Gridley K.E., Green P.S., Simpkins J.W. Low concentrations of estradiol reduce beta-amyloid (25-35)-induced toxicity, lipid peroxidation and glucose utilization in human SK-N-SH neuroblastoma cells. Brain Res. 1997, 778:158-165.
23. Gridley K.E., Green P.S., Simpkins J.W. A novel, synergistic interaction between 17 beta-estradiol and glutathione in the protection of neurons against beta-amyloid 25-35-induced toxicity in vitro. Mol. Pharmacol. 1998, 54:874-880.
24. Grodstein F., Manson J.E., Stampfer M.J. Hormone therapy and coronary heart disease: the role of time sincemenopause and age at hormone initiation. J. Womens Health (Larchmt) 2006, 15:35-44.
25. Harman S.M. What do hormones have to do with aging? What does aging have to do with hormones?. Ann. NY Acad. Sci. 2004, 1019:299-308.
26. Harukuni I., Hurn P.D., Crain B.J. Deleterious effect of 17β-estradiol in a rat model of transient forebrain ischemia. Brain Res. 2001, 900:137-142.
27. Hodis H.N., Mack W.J., Lobo R.A. Randomized controlled trial evidence that estrogen replacement therapy reduces the progression of subclinical atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease. Circulation 2003, 108:e5. author reply e5.
28. Jauslin M.L., Wirth T., Meier T., Shoumacher F. A cellular model for Friedreich Ataxia reveals small-molecule glutathione peroxidase mimetics as novel treatment strategy. Hum. Mol. Genet. 2002, 11:3055-3063.
29. Jauslin M.L., Meier T., Smith R.A., Murphy M.P. Mitochondria-targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. FASEB J. 2003, 17:1972-1974.
30. Liao S., Chen W., Kuo J., Chen C. Association of serum estrogen level and ischemic neuroprotection in female rats. Neurosci. Lett. 2001, 297:159-162.
31. Liu R., Yang S.H., Perez E., Yi K.D., Wu S.S., Eberst K., Prokai L., Prokai-Tatrai K., Cai Z.Y., Covey D.F., Day A.L., Simpkins J.W. Neuroprotective effects of a novel non-receptor-binding estrogen analogue: in vitro and in vivo analysis. Stroke 2002, 33:2485-2491.
32. Maki P.M. Potential importance of early initiation of hormone therapy for cognitive benefit. Menopause 2006, 13:6-7.
33. Manson J.E., Allison M.A., Rossouw J.E., Carr J.J., Langer R.D., Hsia J., Kuller L.H., Cochrane B.B., Hunt J.R., Ludlam S.E., Pettinger M.B., Gass M., Margolis K.L., Nathan L., Ockene J.K., Prentice R.L., Robbins J., Stefanick M.L. Estrogen therapy and coronary-artery calcification. N. Engl. J. Med. 2007, 356:2591-2602.
34. McCullough L.D., Alkayed N.J., Traystman R.J., Williams M.J., Hurn P.D. Postischemic estrogen reduces hypoperfusion and secondary ischemia after experimental stroke. Stroke 2001, 32:796-802.
35. Moosmann B., Behl C. The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:8867-8872.
36. Paganini-Hill A., Henderson V.W. Estrogen replacement therapy and risk of Alzheimer disease. Arch. Intern. Med. 1996, 156:2213-2217.
37. Perez E., Liu R., Yang S.H., Cai Z.Y., Covey D.F., Simpkins J.W. Neuroprotective effects of an estratriene analog are estrogen receptor independent in vitro and in vivo. Brain Res. 2005, 1038:216-222.
38. Perez E., Cai Zu., Yun Covey, Douglas F., Simpkins James W. Neuroprotective effects of estratriene analogs: structure-activity relationships and molecular optimization. Drug Dev. Res. 2005, 66:78-92.
39. Prokai L., Prokai-Tatrai K., Perjesi P., Zharikova A.D., Perez E.J., Liu R., Simpkins J.W. Quinol-based cyclic antioxidant mechanism in estrogen neuroprotection. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:11741-11746.
40. Prokai L., Prokai-Tatrai K., Perjesi P., Zharikova A.D., Simpkins J.W. Quinol-based metabolic cycle for estrogens in rat liver microsomes. Drug Metab. Dispos. 2003, 31:701-704.
41. Resnick S.M., Espeland M.A., Jaramillo S.A., Hirsch C., Stefanick M.L., Murray A.M., Ockene J., Davatzikos C. Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study. Neurology 2009, 72:135-142.
42. Richardson T.E., Yang S.H., Wen Y., Simpkins J.W. Estrogen protection in Friedreich's ataxia skin fibroblasts. Endocrinology 2011, 152:2742-2749.
43. Roth A., Schaffner W., Hertel C. Phytoestrogen kaempferol (3, 4', 5, 7-tetrahydroxyflavone) protects PC12 and T47D cells from beta-amyloid-induced toxicity. J. Neurosci. Res. 1999, 57:399-404.
44. Salpeter S.R., Walsh J.M., Greyber E., Salpeter E.E. Brief report: Coronary heart disease events associated with hormone therapy in younger and older women. A meta-analysis. J. Gen. Intern. Med. 2006, 21:363-366.
45. Santizo R.A., Xu H.L., Ye S., Baughman V.L., Pelligrino D.A. Loss of benefit from estrogen replacement therapy in diabetic ovariectomized female rats subjected to transient forebrain ischemia. Brain Res. 2002, 956:86-95.
46. Sarkar S., Huang R.-Q., Logan S., Dillon G.H., Simpkins J.W. Estrogens directly potentiate neuronal L-type Ca2 channels. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:15148-15153.
47. Shelly W., Draper M.W., Krishnan V., Wong M., Jaffe R.B. Selective estrogen receptor modulators: an update on recent clinical findings. Obstet. Gynecol. Surv. 2008, 63:163-181.
48. Shi J., Bui J.D., Yang S.H., He Z., Lucas T.H., Buckley D.L., Blackband S.J., King M.A., Day A.L., Simpkins J.W. Estrogens decrease reperfusion-associated cortical ischemic damage: an MRI analysis in a transient focal ischemia model. Stroke 2001, 32:987-992.
49. Shughrue P.J., Merchenthaler I. Estrogen prevents the loss of CA1 hippocampal neurons in gerbils after ischemic injury. Neuroscience 2003, 116:851-861.
50. Simpkins J.W., Green P.S., Gridley K.E., Singh M., de Fiebre N.C., Rajakumar G. Role of estrogen replacement therapy in memory enhancement and the prevention of neuronal loss associated with Alzheimer's disease. Am. J. Med. 1997, 103:19S-25S.
51. Simpkins J.W., Rajakumar G., Zhang Y.Q., Simpkins C.E., Greenwald D., Yu C.J., Bodor N., Day A.L. Estrogens may reduce mortality and ischemic damage caused bymiddle cerebral artery occlusion in the female rat. J. Neurosurg. 1997, 87:724-730.
52. Simpkins J.W., Yang S.H., Liu R., Perez E., Cai Z.Y., Covey D.F., Green P.S. Estrogen-like compounds for ischemic neuroprotection. Stroke 2004, 35:2648-2651.
53. Simpkins J.W., Wang J., Wang X., Perez E., Prokai L., Dykens J.A. Mitochondria play a central role in estrogen-induced neuroprotection. Curr. Drug Targets CNS Neurol. Disord. 2005, 4:69-83.
54. Simpkins J.W., Perez E., Wang X., Yang S., Wen Y., Singh M. The potential for estrogens in preventing Alzheimer's disease and vascular dementia. Ther. Adv. Neurol. Disord. 2009, 2:31-49.
55. Sontag E., Luangpirom A., Hladik C., Mudrak I., Ogris E., Speciale S., White C.L. Altered expression levels of the protein phosphatase 2A ABalphaC enzyme are associated with Alzheimer disease pathology. J. Neuropathol. Exp. Neurol. 2004, 63:287-301.
56. Sudo S., Wen T.C., Desaki J., Matsuda S., Tanaka J., Arai T., Maeda N., Sakanaka M. Beta-estradiol protects hippocampal CA1 neurons against transient forebrain ischemia in gerbil. Neurosci. Res. 1997, 29:345-354.
57. Teepker M., Anthes N., Krieg J.C., Vedder H. 2-OH-estradiol, an endogenous hormone with neuroprotective functions. J. Psychiatr. Res. 2003, 37:517-523.
58. Toung T.K., Hurn P.D., Traystman R.J., Sieber F.E. Estrogen decreases infarct size after temporary focal ischemia in a genetic model of type 1 diabetes mellitus. Stroke 2000, 31:2701-2706.
59. Wang C.N., Chi C.W., Lin Y.L., Chen C.F., Shiao Y.J. The neuroprotective effects of phytoestrogens on amyloid beta protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons. J. Biol. Chem. 2001, 276:5287-5295.
60. Yang S.H., Shi J., Day A.L., Simpkins J.W. Estradiol exerts neuroprotective effects when administered after ischemic insult. Stroke 2000, 31:745-749. discussion 749-50.
61. Zandi P.P., Carlson M.C., Plassman B.L., Welsh-Bohmer K.A., Mayer L.S., Steffens D.C., Breitner J.C. Hormone replacement therapy and incidence of Alzheimer disease inolder women: the Cache County Study. JAMA 2002, 288:2123-2129.
62. Zhao L., Chen S., Brinton R.D. An estrogen replacement therapy containing nine synthetic plant-based conjugated estrogens promotes neuronal survival. Exp. Biol. Med. (Maywood) 2003, 228(7):823-835. (Jul).
63. Zhao L., O'Neill K., Brinton R.D. Estrogenic agonist activity of ICI 182,780 (Faslodex) in hippocampal neurons: implications for basic science understanding of estrogen signaling and development of estrogen modulators with a dual therapeutic profile. J. Pharmacol. Exp. Ther. 2006, 319:1124-1132.