Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis
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 molecul...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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IMR Press
2020-12-01
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| Series: | Journal of Integrative Neuroscience |
| Subjects: | |
| Online Access: | https://jin.imrpress.com/fileup/1757-448X/PDF/1609231250911-842876839.pdf |
| _version_ | 1818006406360465408 |
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| author | Min-Fang Guo Hui-Yu Zhang Pei-Jun Zhang Xiao-Qin Liu Li-Juan Song Wen-Yue Wei Yu-Yin Wang Bing-Tao Mu Zhi Chai Jie-Zhong Yu Cun-Gen Ma |
| author_facet | Min-Fang Guo Hui-Yu Zhang Pei-Jun Zhang Xiao-Qin Liu Li-Juan Song Wen-Yue Wei Yu-Yin Wang Bing-Tao Mu Zhi Chai Jie-Zhong Yu Cun-Gen Ma |
| author_sort | Min-Fang Guo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T05:01:38Z |
| format | Article |
| id | doaj.art-79a592c5223f4068bd88517cadaa395b |
| institution | Directory Open Access Journal |
| issn | 0219-6352 |
| language | English |
| last_indexed | 2024-04-14T05:01:38Z |
| publishDate | 2020-12-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Journal of Integrative Neuroscience |
| spelling | doaj.art-79a592c5223f4068bd88517cadaa395b2022-12-22T02:10:54ZengIMR PressJournal of Integrative Neuroscience0219-63522020-12-0119465166210.31083/j.jin.2020.04.2431609231250911-842876839Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axisMin-Fang Guo0Hui-Yu Zhang1Pei-Jun Zhang2Xiao-Qin Liu3Li-Juan Song4Wen-Yue Wei5Yu-Yin Wang6Bing-Tao Mu7Zhi Chai8Jie-Zhong Yu9Cun-Gen Ma10Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, 037009, Datong, P. R. ChinaInstitute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, 037009, Datong, P. R. ChinaInstitute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, 037009, Datong, P. R. ChinaInstitute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, 037009, Datong, P. R. ChinaResearch 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, 030619, Jinzhong, P. R. ChinaInstitute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, 037009, Datong, P. R. ChinaInstitute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, 037009, Datong, P. R. ChinaInstitute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, 037009, Datong, P. R. ChinaResearch 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, 030619, Jinzhong, P. R. ChinaInstitute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, 037009, Datong, P. R. ChinaInstitute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, 037009, Datong, P. R. ChinaRecent 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.https://jin.imrpress.com/fileup/1757-448X/PDF/1609231250911-842876839.pdffasudilalzheimer's diseaseβ-amyloidapoptosisnogo-a/ngr/rhoahyper-phosphorylated tau (p-tau) |
| spellingShingle | Min-Fang Guo Hui-Yu Zhang Pei-Jun Zhang Xiao-Qin Liu Li-Juan Song Wen-Yue Wei Yu-Yin Wang Bing-Tao Mu Zhi Chai Jie-Zhong Yu Cun-Gen Ma Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis Journal of Integrative Neuroscience fasudil alzheimer's disease β-amyloid apoptosis nogo-a/ngr/rhoa hyper-phosphorylated tau (p-tau) |
| title | Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis |
| title_full | Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis |
| title_fullStr | Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis |
| title_full_unstemmed | Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis |
| title_short | Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis |
| title_sort | fasudil reduces β amyloid levels and neuronal apoptosis in app ps1 transgenic mice via inhibition of the nogo a ngr rhoa signaling axis |
| topic | fasudil alzheimer's disease β-amyloid apoptosis nogo-a/ngr/rhoa hyper-phosphorylated tau (p-tau) |
| url | https://jin.imrpress.com/fileup/1757-448X/PDF/1609231250911-842876839.pdf |
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