ArticleJournal of Alzheimer's disease : JAD2023
RhoA-LIMK Signaling Axis Reveals Rostral-Caudal Plane and Spatial Dysregulation in the Brain of Alzheimer's Disease Mouse Models.
Article in Journal of Alzheimer's disease : JAD, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 5 citations in OpenAlex.
- Multi-omics analysis of druggable genes to facilitate Alzheimer's disease therapy: A multi-cohort machine learning study.The journal of prevention of Alzheimer's disease · 2025Article
- The role of small GTPases in Alzheimer's disease tau pathologies.Frontiers in cellular neuroscience · 2025Review
- Spatial and planar profiling of Rac1/Cdc42 signaling in Alzheimer's disease brain.Journal of Alzheimer's disease : JAD · 2024Article
- Enabling systemic identification and functionality profiling for Cdc42 homeostatic modulators.Communications chemistry · 2024Article
- G-Protein Signaling in Alzheimer's Disease: Spatial Expression Validation of Semi-supervised Deep Learning-Based Computational Framework.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRhoA signaling is widely reported to be dysregulated in Alzheimer's disease (AD), but its therapeutic targeting demonstrated mixed outcomes. We hypothesize that the activation and inactivation states of RhoA and LIMK are different in the cortex and in subregions of hippocampus along the rostral-caudal dimensions.
objectiveWe intended to elucidate the plane and spatial dependent RhoA signaling in association with AD.
methodsWe applied antibody pRhoA that recognizes an inactive state of RhoA (S188 phosphorylation) and antibody pLIMK against an active state of LIMK (T508 phosphorylation) to investigate RhoA signaling in wildtype (WT) and triple transgenic AD (3xTg-AD) mouse model. We prepared serial sections from the rostral to caudal coronal planes of the entire mouse brain followed by immunofluorescence staining with pRhoA and pLIMK antibodies.
resultsBoth pRhoA and pLIMK elicited a shift of expression pattern from rostral to caudal planes. Additionally, pRhoA demonstrated dynamic redistribution between the nucleus and cytoplasm. pLIMK did not show such nucleus and cytoplasm redistribution but the expression level was changed from rostral to caudal planes. At some planes, pRhoA showed an increasing trend in expression in the cortex but a decreasing trend in the dentate gyrus of the 3xTg-AD mouse hippocampus. pLIMK tends to decrease in the cortex but increase in the dentate gyrus of 3xTg-AD mouse hippocampus.
conclusionsRhoA activation is dysregulated in both human and mouse AD brains, and the RhoA-LIMK signaling axis reveals spatial dysregulation along the rostral-caudal plane dimensions.
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