TY - JOUR
T1 - Estrogen regulation of Dkk1 and Wnt/β-Catenin signaling in neurodegenerative disease
AU - Scott, Erin L.
AU - Brann, Darrell W.
N1 - Funding Information:
The authors' research presented in this review was supported by a research grant to DWB from the NINDS ( NS050730 ) and a pre-doctoral fellowship to ELS from the American Heart Association ( 12PRE11530009 ).
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
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U2 - 10.1016/j.brainres.2012.12.015
DO - 10.1016/j.brainres.2012.12.015
M3 - Article
C2 - 23261660
AN - SCOPUS:84878500600
SN - 0006-8993
VL - 1514
SP - 63
EP - 74
JO - Brain Research
JF - Brain Research
ER -