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Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system
Authors:Julia J Segura-Uribe  Rodolfo Pinto-Almazán  Angélica Coyoy-Salgado  Claudia E Fuentes-Venado  Christian Guerra-Araiza
Abstract:Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonis-tic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacter-ic symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1 (MAP1), MAP2, neurofilament 38 (NF38) by different mechanisms of action and at different levels: neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neuro-degenerative diseases since they present the benefits of estrogens without their side effects.
Keywords:estrogen receptor modulators  selective estrogen receptor modulators  microtubules  neurofilaments  tibolone  tamoxifen  raloxifene
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