scholarly journals Effects of RedLiriope platyphyllaon NGF secretion ability, NGF receptor signaling pathway and γ-secretase components in NSE/hAPPsw transgenic mice expressing Alzheimer's Disease

2012 ◽  
Vol 28 (3) ◽  
pp. 155 ◽  
Author(s):  
Sun-Il Choi ◽  
Jun-Seo Goo ◽  
Ji-Eun Kim ◽  
In-Sik Hwang ◽  
Hye-Ryun Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Signaling Pathway ◽  
Receptor Signaling ◽  
Ngf Receptor ◽  
Receptor Signaling Pathway

Inhibiting α1-adrenergic Receptor Signaling Pathway Ameliorates Alzheimer’s Disease Type Pathologies and Behavioral Deficits in an AD Mouse Model

2021 ◽  
Author(s):  
Zhong-Yuan Yu ◽  
Xu Yi ◽  
Ye-Ran Wang ◽  
Gui-Hua Zeng ◽  
Cheng-Rong Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Neuronal Loss ◽  
Behavioral Deficits ◽  
Bace1 Expression ◽  
Receptor Signaling Pathway ◽  
Gsk 3Β

Abstract Background The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer’s disease (AD) has rarely been investigated. Clarifying pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic target of AD. Methods This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or equal saline for 6 months. SH-SY5Y cell lines bearing human Amyloid precurssor protein were treated with terazosin or saline for investigating possible mechanisms. Results α1-ARs knockdown mice exhibited improved behavioral performances than control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aβ species, compact and total plaques, than control mice. The α1-ARs inhibitor terazosin substantially reduced Aβ deposition, attenuated downstream pathologies including Tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction, and rescued behavioral deficits of APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3β, thus reduced Aβ production. Conclusions This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.

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