Selective estrogen receptor modulators (SERM) for the brain:: Recent advances and remaining challenges for developing a NeuroSERM™

被引:11
作者
Brinton, RD
机构
[1] Univ So Calif, Pharmaceut Sci Ctr, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90089 USA
[2] Univ So Calif, Pharmaceut Sci Ctr, Program Neurosci, Los Angeles, CA 90089 USA
关键词
estrogen; SERM; nafoxidene; tamoxifen; phytoestrogen; neurodegeneration; Alzheimer's disease;
D O I
10.1002/ddr.10090
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Estrogen regulation of cognitive function and prevention of neurodegenerative disease has come to be of major scientific and clinical importance. While these functions rank paramount among concerns of women during menopause, the neoplastic risks associated with estrogen and hormone replacement therapy lead most women to elect against hormone intervention during menopause or to seek alternative estrogens in an attempt to ameliorate menopause-associated deficits and disease risks. Development of an effective selective estrogen receptor modulator (SERM) for use as an alternative to hormone replacement therapy must address the issues of efficacy in and availability to the brain. A brief review of estrogen effects on cognition, neuroprotective capability, and disease prevention is provided followed by an analysis of current knowledge regarding SERM efficacy in brain. Lastly, the challenges that remain for developing an effective NeuroSERM(TM) are considered.
引用
收藏
页码:380 / 392
页数:13
相关论文
共 107 条
[1]   INHIBITION OF HUMAN AROMATASE BY MAMMALIAN LIGNANS AND ISOFLAVONOID PHYTOESTROGENS [J].
ADLERCREUTZ, H ;
BANNWART, C ;
WAHALA, K ;
MAKELA, T ;
BRUNOW, G ;
HASE, T ;
AROSEMENA, PJ ;
KELLIS, JT ;
VICKERY, LE .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1993, 44 (02) :147-153
[2]  
Anthony M, 2001, ANN NY ACAD SCI, V949, P261
[3]   Reproductive endocrine and endometrial effects of raloxifene hydrochloride, a selective estrogen receptor modulator, in women with regular menstrual cycles [J].
Baker, VL ;
Draper, M ;
Paul, S ;
Allerheiligen, S ;
Glant, M ;
Shifren, J ;
Jaffe, RB .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (01) :6-13
[4]  
Balabhadrapathruni S, 2000, ONCOL REP, V7, P3
[5]   The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus [J].
Bi, RF ;
Broutman, G ;
Foy, MR ;
Thompson, RF ;
Baudry, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3602-3607
[6]   Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway [J].
Bi, RF ;
Foy, MR ;
Vouimba, RM ;
Thompson, RF ;
Baudry, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (23) :13391-13395
[7]   The role of estrogen in the treatment of Alzheimer's disease [J].
Birge, SJ .
NEUROLOGY, 1997, 48 (05) :S36-S41
[8]   Resveratrol acts as a mixed agonist/antagonist for estrogen receptors α and β [J].
Bowers, JL ;
Tyulmenkov, VV ;
Jernigan, SC ;
Klinge, CM .
ENDOCRINOLOGY, 2000, 141 (10) :3657-3667
[9]  
Brink N S, 1998, J NeuroAIDS, V2, P99, DOI 10.1300/J128v02n01_07
[10]   17-BETA-ESTRADIOL INDUCTION OF FILOPODIAL GROWTH IN CULTURED HIPPOCAMPAL-NEURONS WITHIN MINUTES OF EXPOSURE [J].
BRINTON, RD .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1993, 4 (01) :36-46