Evidence map›Paper›PMID 20053478›Full record

ArticleNeurobiology of aging2011

17β-Estradiol regulates insulin-degrading enzyme expression via an ERβ/PI3-K pathway in hippocampus: relevance to Alzheimer's prevention.

Liqin Zhao, Jia Yao, Zisu Mao, Shuhua Chen, Yan Wang, Roberta Diaz Brinton

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of aging, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 122 citations in OpenAlex.

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  10. Sex Differences in Central Amygdala Glutamate Responses to Calcitonin Gene-Related Peptide.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Liqin ZhaoDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA. liqinz@usc.edu
Jia Yao
Zisu Mao
Shuhua Chen
Yan Wang
Roberta Diaz Brinton
University of Southern California · US

Funding

Timing of Menopausal Hormone Therapy across Perimenopause to Menopause Transition: Neuroimmune System in BrainP01AG026572 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Schantel Williams · 2006 to 2026
$53.7M
Estrogen-Induced Neuroprotective Mitochondrial MechanismR01AG032236 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BRINTON, ROBERTA EILEEN · 2009 to 2013
$1.6M
Estrogen-Induced Neuroprotective Mitochondrial MechanismR01MH067159 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BRINTON, ROBERTA DIAZ · 2003 to 2007
$1.3M
NIA NIH HHS P01 AG026572NIA NIH HHS R01 AG032236NIMH NIH HHS R01 MH067159
6 · The paper itself

Abstract

Insulin-degrading enzyme (IDE), an enzyme that primarily degrades insulin, has recently been demonstrated to play a significant role in the catabolism of amyloid β (Aβ) protein in the brain. Reduced IDE expression and/or activity have been associated with the etiology and development of Alzheimer's disease (AD). Using three model systems, the present investigation provides the first documentation indicating that estrogen robustly regulates the expression of IDE in normal, menopausal and early-stage AD brains. In vitro analyses in primary cultures of rat hippocampal neurons revealed that 17β-estradiol (17β-E2) increased IDE in both mRNA and protein levels in a time-dependent manner. Further pharmacological analyses indicated that 17β-E2-induced IDE expression was dependent upon estrogen receptor (ER) β and required activation of phosphatidylinositol 3-kinase (PI3-K). In vivo analyses in adult female rats revealed a brain region-specific responsive profile. Ovariectomy (OVX) induced a significant decline in IDE expression in the hippocampus, which was prevented by 17β-E2. Neither OVX nor 17β-E2 affected IDE expression in the cerebellum. In vivo analyses in triple transgenic AD (3xTg-AD) female mice revealed an inverse correlation between the age-related increase in Aβ load and the decrease in IDE expression in the hippocampal formation. Treatment with 17β-E2 attenuated Aβ accumulation/plaque formation and elevated hippocampal IDE expression in 12-month-old 3xTg-AD OVX mice. Collectively, these findings indicate that 17β-E2 regulates IDE expression in a brain region-specific manner and such a regulatory role in the hippocampus, mediated by an ERβ/PI3-K pathway, could serve as a direct mechanism underlying estrogen-mediated preventative effect against AD when initiated at the onset of menopause.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsCells, CulturedEstradiolEstrogen Receptor betaFemaleHippocampusInsulysinMiceMice, TransgenicNeuronsOvariectomyPhosphatidylinositol 3-KinasesRatsSignal TransductionAmyloid beta-PeptidesEstradiolEstrogen Receptor betaInsulysinPhosphatidylinositol 3-Kinases

Identifiers

PMID20053478
PMCPMC2889185
OpenAlexW2151638758

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.