4.6 Review

The Critical Period for Neuroprotection by Estrogen Replacement Therapy and the Potential Underlying Mechanisms

期刊

CURRENT NEUROPHARMACOLOGY
卷 18, 期 6, 页码 485-500

出版社

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1570159X18666200123165652

关键词

Estrogen; neuroprotection; ischemic stroke; alzheimer's disease; parkinson's disease; menopause; critical period; hormone therapy

资金

  1. Natural Science Foundation of China [81801138, 81801193, 81971226]
  2. Beijing Municipal Science AMP
  3. Technology Commission [1811000017180022]
  4. Beijing Natural Science Foundation [7194321]
  5. Miaopu Foundation of Chinese PLA General Hospital [18KMM47]

向作者/读者索取更多资源

17 beta-Estradiol (estradiol or E2) is a steroid hormone that has been broadly applied as a neuroprotective therapy for a variety of neurodegenerative and cerebrovascular disorders such as ischemic stroke, Alzheimer's disease, and Parkinson's disease. Several laboratory and clinical studies have reported that Estrogen Replacement Therapy (ERT) had no effect against these diseases in elderly postmenopausal women, and at worst, increased their risk of onset and mortality. This review focuses on the growing body of data from in vitro and animal models characterizing the potential underlying mechanisms and signaling pathways that govern successful neuroprotection by ERT, including the roles of E2 receptors in mediating neuroprotection, E2 genomic regulation of apoptosis-related pathways, membrane-bound receptor-mediated non-genomic signaling pathways, and the antioxidant mechanisms of E2. Also discussed is the current evidence for a critical period of effective treatment with estrogen following natural or surgical menopause and the outcomes of E2 administration within an advantageous time period. The known mechanisms governing the duration of the critical period include depletion of E2 receptors, the switch to a ketogenic metabolic profile by neuronal mitochondria, and a decrease in acetylcholine that accompanies E2 deficiency. Also the major clinical trials and observational studies concerning postmenopausal Hormone Therapy (HT) are summarized to compare their outcomes with respect to neurological disease and discuss their relevance to the critical period hypothesis. Finally, potential controversies and future directions for this field are discussed throughout the review.

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