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The estrogen receptor is not essential for all estrogen neuroprotection: new evidence from a new analog.
Neurobiol Dis. 2002 Apr; 9(3):282-93.ND

Abstract

We synthesized an estrogen analog, ZYC-5, lacking activity at the classical estrogen receptor and examined its neuroprotective potential against necrosis induced by N-methyl-d-aspartate (NMDA) and apoptosis/necrosis induced by the NMDA receptor antagonist (+)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP). ZYC-5 protected cortical neurons in a dose-dependent manner, and the neuroprotection was more robust than with 17beta-estradiol. The effect of ZYC-5 was not mediated by the classical estrogen receptor, because it was unaffected by the antagonists 4-hydroxytamoxifen and ICI 182,780. The ZYC-5 protection against excitotoxicity was not directly mediated through the NMDA receptor, because there was no effect of ZYC-5 on NMDA current or the intracellular calcium increase induced by NMDA. Results obtained with the free-radical-sensitive dye, dihydroethidium, suggested that the neuroprotection of ZYC-5 was partly related to its radical scavenging properties. Although some of estrogen's neuroprotective effects may depend upon the estrogen receptor, our results suggest the possibility of neuroprotection without hormonal side effects.

Authors+Show Affiliations

Department of Neurology, Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11950274

Citation

Xia, Shuli, et al. "The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence From a New Analog." Neurobiology of Disease, vol. 9, no. 3, 2002, pp. 282-93.
Xia S, Cai ZY, Thio LL, et al. The estrogen receptor is not essential for all estrogen neuroprotection: new evidence from a new analog. Neurobiol Dis. 2002;9(3):282-93.
Xia, S., Cai, Z. Y., Thio, L. L., Kim-Han, J. S., Dugan, L. L., Covey, D. F., & Rothman, S. M. (2002). The estrogen receptor is not essential for all estrogen neuroprotection: new evidence from a new analog. Neurobiology of Disease, 9(3), 282-93.
Xia S, et al. The Estrogen Receptor Is Not Essential for All Estrogen Neuroprotection: New Evidence From a New Analog. Neurobiol Dis. 2002;9(3):282-93. PubMed PMID: 11950274.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The estrogen receptor is not essential for all estrogen neuroprotection: new evidence from a new analog. AU - Xia,Shuli, AU - Cai,Zu Yun, AU - Thio,Liu Lin, AU - Kim-Han,Jeong Sook, AU - Dugan,Laura L, AU - Covey,Douglas F, AU - Rothman,Steven M, PY - 2002/4/13/pubmed PY - 2002/8/14/medline PY - 2002/4/13/entrez SP - 282 EP - 93 JF - Neurobiology of disease JO - Neurobiol Dis VL - 9 IS - 3 N2 - We synthesized an estrogen analog, ZYC-5, lacking activity at the classical estrogen receptor and examined its neuroprotective potential against necrosis induced by N-methyl-d-aspartate (NMDA) and apoptosis/necrosis induced by the NMDA receptor antagonist (+)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP). ZYC-5 protected cortical neurons in a dose-dependent manner, and the neuroprotection was more robust than with 17beta-estradiol. The effect of ZYC-5 was not mediated by the classical estrogen receptor, because it was unaffected by the antagonists 4-hydroxytamoxifen and ICI 182,780. The ZYC-5 protection against excitotoxicity was not directly mediated through the NMDA receptor, because there was no effect of ZYC-5 on NMDA current or the intracellular calcium increase induced by NMDA. Results obtained with the free-radical-sensitive dye, dihydroethidium, suggested that the neuroprotection of ZYC-5 was partly related to its radical scavenging properties. Although some of estrogen's neuroprotective effects may depend upon the estrogen receptor, our results suggest the possibility of neuroprotection without hormonal side effects. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/11950274/The_estrogen_receptor_is_not_essential_for_all_estrogen_neuroprotection:_new_evidence_from_a_new_analog_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S096999610290478X DB - PRIME DP - Unbound Medicine ER -