ArticleActa neuropathologica communications2018
Rac1 activation links tau hyperphosphorylation and Aβ dysmetabolism in Alzheimer's disease.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Neurodevelopmental Clues to Neurodegeneration.Pediatric neurology · 2021Pooled it
- Plasma-Derived miRNAs as Fluid Biomarkers to Differentiate Alzheimer's and Frontotemporal Dementia.Current issues in molecular biology · 2026Article
- Senescence as a Central Node in Alzheimer's Disease: Molecular Triggers, Cellular Effectors, and RNA-Based Interventions.Neurochemical research · 2026Review
- Mechanistic Role of Astrocytic Rac1 Protein in Alzheimer's Disease.Aging and disease · 2025Review
- A New Molecular Mechanism for the Late-Onset Alzheimer's Disease Risk Gene CD2AP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 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
- The WAVE complex in developmental and adulthood brain disorders.Experimental & molecular medicine · 2025Review
- Resilience mechanisms underlying Alzheimer's disease.Metabolic brain disease · 2025Review
- 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
- Presenilin2 D439A Mutation Induces Dysfunction of Mitochondrial Fusion/Fission Dynamics and Abnormal Regulation of GTPase Activity.Molecular neurobiology · 2024Article
- Analysis of the longitudinal stability of human plasma miRNAs and implications for disease biomarkers.Scientific reports · 2024Article
- Hippocampal CA1 Pyramidal Neurons Display Sublayer and Circuitry Dependent Degenerative Expression Profiles in Aged Female Down Syndrome Mice.Journal of Alzheimer's disease : JAD · 2024Article
- Roles of Rac1-Dependent Intrinsic Forgetting in Memory-Related Brain Disorders: Demon or Angel.International journal of molecular sciences · 2023Review
- Novel approaches to increase synaptic resilience as potential treatments for Alzheimer's disease.Seminars in cell & developmental biology · 2023Review
- Increased Expression of Autophagy-Related Genes in Alzheimer's Disease-Type 2 Diabetes Mellitus Comorbidity Models in Cells.International journal of environmental research and public health · 2023Article
- RhoA-LIMK Signaling Axis Reveals Rostral-Caudal Plane and Spatial Dysregulation in the Brain of Alzheimer's Disease Mouse Models.Journal of Alzheimer's disease : JAD · 2023Article
- Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders.Frontiers in cellular neuroscience · 2023Review
- Accelerated long-term forgetting: A sensitive paradigm for detecting subtle cognitive impairment and evaluating BACE1 inhibitor efficacy in preclinical Alzheimer's disease.Frontiers in dementia · 2023Review
- Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity.NPJ Parkinson's disease · 2022Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
One of the earliest pathological features characterizing Alzheimer's disease (AD) is the loss of dendritic spines. Among the many factors potentially mediating this loss of neuronal connectivity, the contribution of Rho-GTPases is of particular interest. This family of proteins has been known for years as a key regulator of actin cytoskeleton remodeling. More recent insights have indicated how its complex signaling might be triggered also in pathological conditions. Here, we showed that the Rho-GTPase family member Rac1 levels decreased in the frontal cortex of AD patients compared to non-demented controls. Also, Rac1 increased in plasma samples of AD patients with Mini-Mental State Examination < 18 compared to age-matched non demented controls. The use of different constitutively active peptides allowed us to investigate in vitro Rac1 specific signaling. Its activation increased the processing of amyloid precursor protein and induced the translocation of SET from the nucleus to the cytoplasm, resulting in tau hyperphosphorylation at residue pT181. Notably, Rac1 was abnormally activated in the hippocampus of 6-week-old 3xTg-AD mice. However, the total protein levels decreased at 7-months. A rescue strategy based on the intranasal administration of Rac1 active peptide at 6.5 months prevented dendritic spine loss. This data suggests the intriguing possibility of a dual role of Rac1 according to the different stages of the pathology. In an initial stage, Rac1 deregulation might represent a triggering co-factor due to the direct effect on Aβ and tau. However, at a later stage of the pathology, it might represent a potential therapeutic target due to the beneficial effect on spine dynamics.
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