Estrogen regulation of Dkk1 and Wnt/β-Catenin signaling in neurodegenerative disease

Erin L. Scott, Darrell W Brann

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

17β-estradiol (E2 or estrogen) is an endogenous steroid hormone that is well known to exert neuroprotection. Along these lines, one mechanism through which E2 protects the hippocampus from cerebral ischemia is by preventing the post-ischemic elevation of Dkk1, a neurodegenerative factor that serves as an antagonist of the canonical Wnt signaling pathway, and simultaneously inducing pro-survival Wnt/β-Catenin signaling in hippocampal neurons. Intriguingly, while expression of Dkk1 is required for proper neural development, overexpression of Dkk1 is characteristic of many neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, and temporal lobe epilepsy. In this review, we will briefly summarize the canonical Wnt signaling pathway, highlight the current literature linking alterations of Dkk1 and Wnt/β-Catenin signaling with neurological disease, and discuss E2's role in maintaining the delicate balance of Dkk1 and Wnt/β-Catenin signaling in the adult brain. Finally, we will consider the implications of long-term E2 deprivation and hormone therapy on this crucial neural pathway. This article is part of a Special Issue entitled Hormone Therapy.

Original languageEnglish (US)
Pages (from-to)63-74
Number of pages12
JournalBrain Research
Volume1514
DOIs
StatePublished - Jun 13 2013

Fingerprint

Catenins
Wnt Signaling Pathway
Neurodegenerative Diseases
Estrogens
Hormones
Neural Pathways
Temporal Lobe Epilepsy
Brain Ischemia
Parkinson Disease
Estradiol
Hippocampus
Alzheimer Disease
Stroke
Steroids
Neurons
Brain
Therapeutics

Keywords

  • Brain
  • Dkk1
  • Estrogen
  • Neurodegenerative disease
  • Wnt signaling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Estrogen regulation of Dkk1 and Wnt/β-Catenin signaling in neurodegenerative disease. / Scott, Erin L.; Brann, Darrell W.

In: Brain Research, Vol. 1514, 13.06.2013, p. 63-74.

Research output: Contribution to journalArticle

@article{c849d535072e49068630b75352e66fc7,
title = "Estrogen regulation of Dkk1 and Wnt/β-Catenin signaling in neurodegenerative disease",
abstract = "17β-estradiol (E2 or estrogen) is an endogenous steroid hormone that is well known to exert neuroprotection. Along these lines, one mechanism through which E2 protects the hippocampus from cerebral ischemia is by preventing the post-ischemic elevation of Dkk1, a neurodegenerative factor that serves as an antagonist of the canonical Wnt signaling pathway, and simultaneously inducing pro-survival Wnt/β-Catenin signaling in hippocampal neurons. Intriguingly, while expression of Dkk1 is required for proper neural development, overexpression of Dkk1 is characteristic of many neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, and temporal lobe epilepsy. In this review, we will briefly summarize the canonical Wnt signaling pathway, highlight the current literature linking alterations of Dkk1 and Wnt/β-Catenin signaling with neurological disease, and discuss E2's role in maintaining the delicate balance of Dkk1 and Wnt/β-Catenin signaling in the adult brain. Finally, we will consider the implications of long-term E2 deprivation and hormone therapy on this crucial neural pathway. This article is part of a Special Issue entitled Hormone Therapy.",
keywords = "Brain, Dkk1, Estrogen, Neurodegenerative disease, Wnt signaling",
author = "Scott, {Erin L.} and Brann, {Darrell W}",
year = "2013",
month = "6",
day = "13",
doi = "10.1016/j.brainres.2012.12.015",
language = "English (US)",
volume = "1514",
pages = "63--74",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

TY - JOUR

T1 - Estrogen regulation of Dkk1 and Wnt/β-Catenin signaling in neurodegenerative disease

AU - Scott, Erin L.

AU - Brann, Darrell W

PY - 2013/6/13

Y1 - 2013/6/13

N2 - 17β-estradiol (E2 or estrogen) is an endogenous steroid hormone that is well known to exert neuroprotection. Along these lines, one mechanism through which E2 protects the hippocampus from cerebral ischemia is by preventing the post-ischemic elevation of Dkk1, a neurodegenerative factor that serves as an antagonist of the canonical Wnt signaling pathway, and simultaneously inducing pro-survival Wnt/β-Catenin signaling in hippocampal neurons. Intriguingly, while expression of Dkk1 is required for proper neural development, overexpression of Dkk1 is characteristic of many neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, and temporal lobe epilepsy. In this review, we will briefly summarize the canonical Wnt signaling pathway, highlight the current literature linking alterations of Dkk1 and Wnt/β-Catenin signaling with neurological disease, and discuss E2's role in maintaining the delicate balance of Dkk1 and Wnt/β-Catenin signaling in the adult brain. Finally, we will consider the implications of long-term E2 deprivation and hormone therapy on this crucial neural pathway. This article is part of a Special Issue entitled Hormone Therapy.

AB - 17β-estradiol (E2 or estrogen) is an endogenous steroid hormone that is well known to exert neuroprotection. Along these lines, one mechanism through which E2 protects the hippocampus from cerebral ischemia is by preventing the post-ischemic elevation of Dkk1, a neurodegenerative factor that serves as an antagonist of the canonical Wnt signaling pathway, and simultaneously inducing pro-survival Wnt/β-Catenin signaling in hippocampal neurons. Intriguingly, while expression of Dkk1 is required for proper neural development, overexpression of Dkk1 is characteristic of many neurodegenerative diseases, such as stroke, Alzheimer's disease, Parkinson's disease, and temporal lobe epilepsy. In this review, we will briefly summarize the canonical Wnt signaling pathway, highlight the current literature linking alterations of Dkk1 and Wnt/β-Catenin signaling with neurological disease, and discuss E2's role in maintaining the delicate balance of Dkk1 and Wnt/β-Catenin signaling in the adult brain. Finally, we will consider the implications of long-term E2 deprivation and hormone therapy on this crucial neural pathway. This article is part of a Special Issue entitled Hormone Therapy.

KW - Brain

KW - Dkk1

KW - Estrogen

KW - Neurodegenerative disease

KW - Wnt signaling

UR - http://www.scopus.com/inward/record.url?scp=84878500600&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878500600&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2012.12.015

DO - 10.1016/j.brainres.2012.12.015

M3 - Article

C2 - 23261660

AN - SCOPUS:84878500600

VL - 1514

SP - 63

EP - 74

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -