Restoring Wnt/β-catenin signaling is a promising therapeutic strategy for Alzheimer's disease

被引：226

作者：

Jia, Lin ^{[1
,2
]}

Pina-Crespo, Juan ^{[3
]}

Li, Yonghe ^{[1
]}

机构：

[1] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA

[2] Xiamen Univ, Coll Med, Fujian Prov Key Lab Neurodegenerat Dis & Aging Re, Inst Neurosci, Xiamen 361102, Peoples R China

[3] Sanford Burnham Prebys Med Discovery Inst, Neurosci Initiat, La Jolla, CA 92037 USA

来源：

MOLECULAR BRAIN | 2019年 / 12卷 / 01期

关键词：

Wnt; Alzheimer's disease; Neuronal survival; Neurogenesis; Synaptic plasticity; Drug target; BLOOD-BRAIN-BARRIER; AMYLOID PRECURSOR PROTEIN; BETA-CATENIN; HIPPOCAMPAL NEUROGENESIS; NERVOUS-SYSTEM; COGNITIVE DEFICITS; ADULT NEUROGENESIS; GENETIC SCREEN; SYNAPSE LOSS; WNT PATHWAY;

D O I：

10.1186/s13041-019-0525-5

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alzheimer's disease (AD) is an aging-related neurological disorder characterized by synaptic loss and dementia. Wnt/beta-catenin signaling is an essential signal transduction pathway that regulates numerous cellular processes including cell survival. In brain, Wnt/beta-catenin signaling is not only crucial for neuronal survival and neurogenesis, but it plays important roles in regulating synaptic plasticity and blood-brain barrier integrity and function. Moreover, activation of Wnt/beta-catenin signaling inhibits amyloid-beta production and tau protein hyperphosphorylation in the brain. Critically, Wnt/beta-catenin signaling is greatly suppressed in AD brain via multiple pathogenic mechanisms. As such, restoring Wnt/beta-catenin signaling represents a unique opportunity for the rational design of novel AD therapies.

引用

页数：11

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