Abstract
The abnormal deposition of the extracellular amyloid-β peptide is the typical pathological hallmark of Alzheimer's disease. Strategies to reduce the amyloid-β deposition effectively alleviate the neuronal degeneration and cognitive deficits of Alzheimer's disease. Danggui-Shaoyao-San has been considered a useful therapeutic agent known for the treatment of Alzheimer's disease. However, the mechanism of Danggui-Shaoyao-San for the treatment of Alzheimer's disease remains unclear. We investigated Danggui-Shaoyao-San's effect on amyloidosis and neuronal degeneration in an APP/PS1 mouse model. We found Danggui-Shaoyao-San alleviated the cognitive deficits in APP/PS1 mice. Additionally, Danggui-Shaoyao-San ameliorated the neuronal degeneration in these mice. Danggui-Shaoyao-San reduced the amyloidosis and amyloid-β1-42 deposition in APP/PS1 mouse brain and down-regulated the receptor for advanced glycation end products, and up-regulated the level of low-density lipoprotein receptor-related protein-1. However, the protein expression of the β-amyloid precursor protein, β-Secretase and presenilin-1 (PS1) in the amyloid-β production pathway, and the expression of neprilysin and insulin-degrading enzyme in the amyloid-β degradation pathway were not altered. Our findings collectively suggest that Danggui-Shaoyao-San could ameliorate the amyloidosis and neuronal degeneration of Alzheimer's disease, which may be associated with its up-regulation lipoprotein receptor-related protein-1 and down-regulation of the receptor for advanced glycation end products.
Highlights
Alzheimer’s disease (AD) is a common neurodegenerative disease that is age-related and features progressive memory decline [1]
A two-month DSS treatment showed no effects on protein levels related to Aβ generation and Aβ degeneration in this study. These findings collectively indicate that DSS can alleviate the neuronal degeneration and amyloidosis of AD, which may be through upregulation of lipoprotein receptor-related protein-1 (LRP1) and down-regulation of receptor for advanced glycation end products (RAGE) (Fig. 7)
We found that DSS effectively alleviates the amyloidosis and neuronal degeneration in the Aβ precursor protein (APP)/PS1 transgenic mouse, which could achieve the same effect as Donepezil
Summary
Alzheimer’s disease (AD) is a common neurodegenerative disease that is age-related and features progressive memory decline [1]. The overproduction and accumulation of Aβ in the brain are tightly related to neuronal cell death in AD. It is reported that the abnormal deposition of Aβ peptides in the brain can induce oxidative stress and neuroinflammation and initiate a cascade of pathologic events, such as tau-hyperphosphorylation, neurite degeneration and neuronal loss [5,6,7]. Aβ1−40 and Aβ1−42 are the primary forms of Aβ peptide Compared with the former, Aβ1−42 is considered more amyloidogenic and toxic in the brain [8]. Low-density lipoprotein receptor-related protein-1 (LRP1) and the receptor for advanced glycation end products (RAGE) are the primary transporters in BBB Aβ transport. Regulating LRP1 and RAGE expression, responsible for Aβ transportation, may be an effective strategy to reduce the abnormal Aβ deposition in AD
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