IMR Press / JIN / Volume 19 / Issue 4 / DOI: 10.31083/j.jin.2020.04.243
Open Access Original Research
Fasudil reduces β -amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis
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1 Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong, 037009, P. R. China
2 Research Center of Neurobiology, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Traditional Chinese Medicine, Jinzhong, 030619, P. R. China
3 Department of Neurology, First Affiliated Hospital, Shanxi Medical University, Taiyuan, 030001, P. R. China
4 Department of Neurology, Datong Fifth People's Hospital, Datong, 037009, P. R. China
*Correspondence: (Jie-Zhong Yu); (Cun-Gen Ma)
J. Integr. Neurosci. 2020, 19(4), 651–662;
Submitted: 13 August 2020 | Revised: 6 October 2020 | Accepted: 20 October 2020 | Published: 30 December 2020
Copyright: © 2020 Guo et al. Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

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.

Alzheimer's disease
β -amyloid
hyper-phosphorylated tau (p-tau)
Fig. 1.
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