Therapy Type: Other
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Approved for: Hormone Replacement Therapy
There are a number of biological mechanisms through which estrogens might exert neuroprotective effects. These include the promotion of cholinergic activity (Gibbs, 2010), increase in the morphological complexity of neurons associated with learning and memory (Brinton et al., 2000), protection from toxic insult (Brinton et al., 2000), stimulation of neuron formation (Tanapat et al., 1999), and reduction of the formation of Aβ (Pike et al., 2009).
Estrogen is a steroid hormone important in the development and maintenance of the female reproductive system and secondary sex characteristics. In addition, in vitro experiments have demonstrated that estrogen can protect cultured neurons from Aβ-related toxicity (Behl et al., 1995; Goodman et al., 1996; Mook-Jung et al., 1997), as well as oxidative stress-related damage (e.g., Behl, 2002). Animal models based on these mechanisms also support potential benefits of estrogen in the CNS. Estrogen is capable of decreasing amyloid accumulation and improving memory performance in ovariectomized rats (Carroll et al., 2007; Shang et al., 2010), and has been shown to enhance long-term potentiation in the hippocampus in these rats (Foy et al., 1999).
- Behl C, Widmann M, Trapp T, Holsboer F. 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Commun. 1995 Nov 13;216(2):473-82. PubMed.
- Goodman Y, Bruce AJ, Cheng B, Mattson MP. Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J Neurochem. 1996 May;66(5):1836-44. PubMed.
- Mook-Jung I, Joo I, Sohn S, Kwon HJ, Huh K, Jung MW. Estrogen blocks neurotoxic effects of beta-amyloid (1-42) and induces neurite extension on B103 cells. Neurosci Lett. 1997 Oct 17;235(3):101-4. PubMed.
- Behl C. Estrogen can protect neurons: modes of action. J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):195-7. PubMed.
- Carroll JC, Rosario ER, Chang L, Stanczyk FZ, Oddo S, Laferla FM, Pike CJ. Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice. J Neurosci. 2007 Nov 28;27(48):13357-65. PubMed.
- Shang XL, Zhao JH, Cao YP, Xue YX. Effects of synaptic plasticity regulated by 17beta-estradiol on learning and memory in rats with Alzheimer's disease. Neurosci Bull. 2010 Apr;26(2):133-9. PubMed.
- Foy MR, Xu J, Xie X, Brinton RD, Thompson RF, Berger TW. 17beta-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation. J Neurophysiol. 1999 Feb;81(2):925-9. PubMed.
- Gibbs RB. Estrogen therapy and cognition: a review of the cholinergic hypothesis. Endocr Rev. 2010 Apr;31(2):224-53. PubMed.
- Brinton RD, Chen S, Montoya M, Hsieh D, Minaya J. The estrogen replacement therapy of the Women's Health Initiative promotes the cellular mechanisms of memory and neuronal survival in neurons vulnerable to Alzheimer's disease. Maturitas. 2000 Apr 1;34 Suppl 2:S35-52. PubMed.
- Tanapat P, Hastings NB, Reeves AJ, Gould E. Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci. 1999 Jul 15;19(14):5792-801. PubMed.
- Pike CJ, Carroll JC, Rosario ER, Barron AM. Protective actions of sex steroid hormones in Alzheimer's disease. Front Neuroendocrinol. 2009 Jul;30(2):239-58. PubMed.
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