中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (8): 1231-1240.doi: 10.4103/1673-5374.213536

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

雌激素受体调节剂影响中枢神经系统中细胞骨架蛋白

  

  • 收稿日期:2017-07-17 出版日期:2017-08-15 发布日期:2017-08-15
  • 基金资助:

    此项研究得到了FIS/IMSS项目(FIS/IMSS/PROT/G13/1216)、IMSS基金会研究优秀奖学金、CIS、墨西哥国家科学技术委员会和USC-CONACYT博士后学者项目的共同赞助支持

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.

摘要:

雌激素受体调节剂(ERM)是具有雌激素激动和拮抗作用的化合物,其在临床有广泛应用,特别是用于绝经后乳腺癌和骨质疏松症以及更年期症状的治疗。与雌激素类似,ERM的神经保护作用已得到研究证实。然而,其在中枢神经系统中的作用机制尚未得到充分理解。 

文中对ERMs在中枢神经系统中的作用,特别是其对细胞骨架蛋白的调控进行了回顾,并发现雷洛昔芬、他莫昔芬和替勃龙通过不同的作用机制,在不同水平(神经元微丝,中间丝和微管相关蛋白)调节细胞骨架蛋白如tau,MAP1,MAP2,NF38。最后,文章强调,由于ERM具有雌激素的益处,却没有其副作用,因而其在治疗神经退行性疾病中的作用具有广阔前景。

orcid:0000-0002-7164-4116(Christian Guerra-Araiza

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