2015
DOI: 10.1126/scitranslmed.aab1290
|View full text |Cite
|
Sign up to set email alerts
|

Abstract: Many neurological and psychiatric maladies originate from the deprivation of the human brain from estrogens. However, current hormone therapies cannot be used safely to treat these conditions commonly associated with menopause because of detrimental side-effects in the periphery. The latter also prevents the use of the hormone for neuroprotection. Here we show that a small-molecule bioprecursor prodrug, 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), converts to 17β-estradiol in the brain after systemic administ… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

6
133
2

Year Published

2016
2016
2022
2022

Publication Types

Select...
9

Relationship

3
6

Authors

Journals

citations
Cited by 49 publications
(141 citation statements)
references
References 53 publications
(84 reference statements)
6
133
2
Order By: Relevance
“…For this, the focus of several studies has turned to synthetic ligands that selectively activate ERb and are thus devoid of undesired carcinogenic effects (47). A previous study highlights the use of the prodrug DHED that is metabolized to estradiol selectively in the brain and could have valuable therapeutic effects on human diseases associated with estrogen-mediated neuroprotection (48), such as multiple sclerosis. In addition, very recent studies by our group shed light on the ERb ligand-mediated regulation of CNS autoimmunity and of Th17 responses, via ERb expression on CD4 + T cells.…”
Section: Discussionmentioning
confidence: 99%
“…For this, the focus of several studies has turned to synthetic ligands that selectively activate ERb and are thus devoid of undesired carcinogenic effects (47). A previous study highlights the use of the prodrug DHED that is metabolized to estradiol selectively in the brain and could have valuable therapeutic effects on human diseases associated with estrogen-mediated neuroprotection (48), such as multiple sclerosis. In addition, very recent studies by our group shed light on the ERb ligand-mediated regulation of CNS autoimmunity and of Th17 responses, via ERb expression on CD4 + T cells.…”
Section: Discussionmentioning
confidence: 99%
“…DHED was prepared according to previously published procedures (Prokai et al, 2015). All other chemicals were purchased from Sigma-Aldrich (St. Louis, MO) unless otherwise stated.…”
Section: Methodsmentioning
confidence: 99%
“…This study is focused on the AD-therapeutic potential of a novel brain-selective E2 prodrug, 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), that spares the periphery from estrogenic stimulation (Prokai et al, 2015). Specifically, we aimed at determining whether DHED treatment would slow the progression of the onset of AD characteristics, including the reduction of Aβ formation and protection against cognitive impairment, by directly comparing with the efficacy of E2 treatment in a well-characterized double-transgenic (DTG) mouse model of the disease (Jankowsky et al, 2004).…”
Section: Introductionmentioning
confidence: 99%
“…In addition, we have the advantageous capacity to evaluate behavioral and brain changes at the cellular and molecular level much more quickly than would be possible using human subjects. This utility affords basic scientists the opportunity to explore novel brain targets and drug delivery methods [136] for favorable cognitive outcomes and healthy brain aging profiles that have the potential to translate to the clinical research setting.…”
Section: 1 Conclusionmentioning
confidence: 99%