Neural Regeneration Research ›› 2017, Vol. 12 ›› Issue (8): 1231-1240.doi: 10.4103/1673-5374.213536

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Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

Julia J. Segura-Uribe1, 2, Rodolfo Pinto-Almazán3, 4, 5, Angélica Coyoy-Salgado1, 6, Claudia E. Fuentes-Venado7, 8, 9, Christian Guerra-Araiza9   

  1. 1 Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico;
    2 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico;
    3 Unidad de Investigación Hospital Regional de Alta Especialidad Ixtapaluca, Ixtapaluca, Mexico;
    4 Institute for the Developing Mind, Children’s Hospital Los Angeles, Los Angeles, CA, USA;
    5 Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA;
    6 Consejo Nacional de Ciencia y Tecnología, Mexico City, Mexico;
    7 Clínica de Trastornos del Sueño, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City, Mexico;
    8 Servicio de Medicina Física y Rehabilitacion, Hospital General de Zona No. 197, Texcoco, Mexico;
    9 Unidad de Investigación Médica en Farmacología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
  • Received:2017-07-17 Online:2017-08-15 Published:2017-08-15
  • Contact: Christian Guerra-Araiza, Ph.D.,christianguerra2001@gmail.com.
  • Supported by:

    This study was supported by FIS/IMSS project No. FIS/IMSS/PROT/G13/1216. CGA received Beca de Excelencia en Investigación by Fundación IMSS, ACS, JJSU received financial support from CIS/IMSS and CONACyT, RPA received financial support from USC-CONACYT Postdoctoral Scholars Program.

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Abstract:

Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic 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 climacteric 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 neurodegenerative diseases since they present the benefits of estrogens without their side effects.

Key words: estrogen receptor modulators, selective estrogen receptor modulators, microtubules, neurofilaments, tibolone, tamoxifen, raloxifene