RhoA/Rock2/Limk1/cofilin1 pathway is involved in attenuation of neuronal dendritic spine loss by paeonol in the frontal cortex of D-galactose and aluminum-induced Alzheimer’s disease-like rat model
Open accessAbstract
Alzheimer's disease (AD) has become the most prevalent neurodegenerative disorder. Given the pathogenesis of AD is unclear, there is currently no drug approved to halt or delay the progression of AD. Therefore, it is pressing to explore new targets and drugs for AD. In China, polyphenolic Chinese herbal medicine has been used for thousands of years in clinical application, and no toxic effects have been reported. In the present study, using D‑galactose and aluminum‑induced rat model, the effects of paeonol on AD were validated via the Morris water maze test, open field test, and elevated plus maze test. Neuronal morphology in frontal cortex was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. RhoA/Rock2/Limk1/cofilin1 signaling pathway‑related molecules were determined by Western blotting. Cofilin1 and p‑cofilin1 were analyzed by immunofluorescence. Results showed that pre‑treatment with paeonol attenuated D‑galactose and aluminum‑induced behavioral dysfunction and AD‑like pathological alterations in the frontal cortex. Accompanied by these changes were the alterations in the dendrite and dendritic spine densities, especially the mushroom‑type and filopodia‑type spines in the apical dendrites, as well as actin filaments. In addition, the activity and intracellular distribution of cofilin1 and the molecules RhoA/Rock2/Limk1 that regulate the signaling pathway for cofilin1 phosphorylation have also changed. Our data suggests that paeonol may be through reducing Aβ levels to alleviate the loss of fibrillar actin and dendrites and dendritic spines via the Rho/Rock2/Limk1/cofilin1 signaling pathway in the frontal cortex, and ultimately improving AD‑like behavior.
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In a D-galactose and aluminum-induced AD-like rat model, paeonol attenuates neuronal dendritic spine loss through inhibition of the RhoA/ROCK/LIMK1/cofilin1 pathway.
“In a D-galactose and aluminum-induced AD-like rat model, paeonol was found to attenuate neuronal dendritic spine loss through inhibition of the RhoA/ROCK/LIMK1/cofilin1 pathway [195].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [195]
The Results section reports that paeonol relieved dendritic spine loss and reduced the model-induced elevations of RhoA and ROCK2; the reported reduction in LIMK1 did not reach conventional significance (P=0.081). The Discussion proposes that the pathway is involved, and the conclusion says it acts “at least in part” through that pathway. The claim presents inhibition of the entire pathway as an established mechanism, stronger than the paper supports. (LLM, conf=0.86)
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Cited by
Sorted by citations
RhoA Signaling in Neurodegenerative Diseases
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- Authors
- Han, F., Xu, H., Shen, J.-X., Pan, C., Yu, Z.-H., Chen, J.-J., Zhu, X.-L., Cai, Y.-F., & Lu, Y.-P.
- Affiliations
- Anhui Normal University (CN)
- Anhui College of Traditional Chinese Medicine (CN)
- Wannan Medical College (CN)
- Venue
- Acta Neurobiologiae Experimentalis
- Published
- 2020
- Volume
- 80
- Issue
- 3
- Pages
- 225-244
- ISSN
- 0065-1400 (ISSN-L)
- 1689-0035
- OpenAlex
- W3091177515
- Cited by
- 18
- References
- 16
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 3
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Acta Neurobiologiae Experimentalis (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, paeonol, dendritic spine loss, actin cytoskeleton, frontal cortex, amyloid-beta, Chinese herbal medicine, cognitive impairment, behavioral dysfunction
- MeSH terms
- Aluminum, Alzheimer Disease, Animals, Galactose, Hippocampus, Neurons, Phosphorylation, rhoA GTP-Binding Protein, Dendritic Spines, Lim Kinases
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