Open AccessFasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis
Author(s) -
Minfang Guo,
Huiyu Zhang,
Peijun Zhang,
Xiaoqin Liu,
Lijuan Song,
Wenyue Wei,
Yuyin Wang,
Bing-Tao Mu,
Zhi Chai,
JieZhong Yu,
Chi Ma
Publication year - 2020
Publication title -
journal of integrative neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.336
H-Index - 33
eISSN - 1757-448X
pISSN - 0219-6352
DOI - 10.31083/j.jin.2020.04.243
Subject(s) - fasudil , rhoa , rho associated protein kinase , genetically modified mouse , signal transduction , microbiology and biotechnology , neuroprotection , synaptophysin , amyloid precursor protein , pathogenesis , alzheimer's disease , cyclin dependent kinase 5 , apoptosis , chemistry , transgene , neuroscience , biology , medicine , disease , protein kinase c , biochemistry , immunohistochemistry , mitogen activated protein kinase kinase , gene
Recent studies have shown that Nogo-A and the Nogo-A receptor affect β-amyloid metabolism and the downstream Rho GTP enzyme signaling pathway, which may affect the levels of β-amyloid and tau. Nogo-A may play a key role in the pathogenesis of Alzheimer's disease. However, the underlying molecular mechanisms of Fasudil treatment in Alzheimer's disease are not yet clear. Our results have found that Fasudil treatment for two months substantially ameliorated behavioral deficits, diminished β-amyloid plaque and tau protein pathology, and alleviated neuronal apoptosis in APP/PS1 transgenic mice. More importantly, two well-established markers for synaptic function, growth-associated protein 43 and synaptophysin, were upregulated after Fasudil treatment. Finally, the levels of Nogo-A, Nogo-A receptor complex NgR/p75NTR/LINGO-1 and the downstream Rho/Rho kinase signaling pathway were significantly reduced. These findings suggest that Fasudil exerts its neuroprotective function in Alzheimer's disease by inhibiting the Nogo-A/NgR1/RhoA signaling pathway.