ArticleHuman molecular genetics2020
Disruption of a RAC1-centred network is associated with Alzheimer's disease pathology and causes age-dependent neurodegeneration.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Plasma-Derived miRNAs as Fluid Biomarkers to Differentiate Alzheimer's and Frontotemporal Dementia.Current issues in molecular biology · 2026Article
- Uncovering Key Genes in Neurodegenerative Diseases Through Unsupervised Learning: A Variance-Based LSTM and Enrichment Analysis Approach.Advances in experimental medicine and biology · 2026Article
- A rapid and dynamic role for FMRP in the plasticity of adult neurons.Nature communications · 2025Article
- Per- and polyfluoroalkyl substances (PFAS) and microRNA: An epigenome-wide association study in firefighters.Environmental research · 2025Article
- Repurposing the memory-promoting meclofenoxate hydrochloride as a treatment for Parkinson's disease through integrative multi-omics analysis.NPJ Parkinson's disease · 2025Article
- Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders.Discover mental health · 2025Article
- Resilience mechanisms underlying Alzheimer's disease.Metabolic brain disease · 2025Review
- Identification of Alzheimer's disease biomarkers and their immune function characterization.Archives of medical science : AMS · 2025Article
- 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
- Gene expression clock: an unsupervised deep learning approach for predicting circadian rhythmicity from whole genome expression.Neural computing & applications · 2024Article
- Identification of female-enriched and disease-associated microglia (FDAMic) contributes to sexual dimorphism in late-onset Alzheimer's disease.Journal of neuroinflammation · 2024Article
- PENN: Phase Estimation Neural Network on Gene Expression Data.The 4th Joint International Conference on Deep Learning, Big Data and Blockchain (DBB 2023). Joint International Conference on Deep Learning, Big Data and Blockchain (4th : 2023 : Marrakech, Morocco ; Online) · 2023Article
- Roles of Rac1-Dependent Intrinsic Forgetting in Memory-Related Brain Disorders: Demon or Angel.International journal of molecular sciences · 2023Review
- Mechanism and Therapeutic Prospect of miRNAs in Neurodegenerative Diseases.Behavioural neurology · 2023Review
- A new perspective on Alzheimer's disease: microRNAs and circular RNAs.Frontiers in genetics · 2023Review
- Review
- Article
- Identification of Ferroptosis-Related Genes in Alzheimer's Disease Based on Bioinformatic Analysis.Frontiers in neuroscience · 2022Article
- A Study on the Correlation Between Age-Related Macular Degeneration and Alzheimer's Disease Based on the Application of Artificial Neural Network.Frontiers in public health · 2022Article
- Application of weighted co-expression network analysis and machine learning to identify the pathological mechanism of Alzheimer's disease.Frontiers in aging neuroscience · 2022Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular biological mechanisms of Alzheimer's disease (AD) involve disease-associated crosstalk through many genes and include a loss of normal as well as a gain of abnormal interactions among genes. A protein domain network (PDN) is a collection of physical bindings that occur between protein domains, and the states of the PDNs in patients with AD are likely to be perturbed compared to those in normal healthy individuals. To identify PDN changes that cause neurodegeneration, we analysed the PDNs that occur among genes co-expressed in each of three brain regions at each stage of AD. Our analysis revealed that the PDNs collapsed with the progression of AD stage and identified five hub genes, including Rac1, as key players in PDN collapse. Using publicly available as well as our own gene expression data, we confirmed that the mRNA expression level of the RAC1 gene was downregulated in the entorhinal cortex (EC) of AD brains. To test the causality of these changes in neurodegeneration, we utilized Drosophila as a genetic model and found that modest knockdown of Rac1 in neurons was sufficient to cause age-dependent behavioural deficits and neurodegeneration. Finally, we identified a microRNA, hsa-miR-101-3p, as a potential regulator of RAC1 in AD brains. As the Braak neurofibrillary tangle (NFT) stage progressed, the expression levels of hsa-miR-101-3p were increased specifically in the EC. Furthermore, overexpression of hsa-miR-101-3p in the human neuronal cell line SH-SY5Y caused RAC1 downregulation. These results highlight the utility of our integrated network approach for identifying causal changes leading to neurodegeneration in AD.
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