ArticleCell death & disease2016
GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte-neuron interactions.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 90 citations in OpenAlex.
- Carbon-12 and Gamma-Rays Combined Irradiation Ameliorates Behavioral and Biochemical Alterations in Tau P301S Homozygous Transgenic Mice.Molecular neurobiology · 2026Article
- PROTAC-mediated multi-target protein degradation in Alzheimer's disease: mechanistic insights, therapeutic applications, and translational challenges.RSC medicinal chemistry · 2026Review
- ZuoGui Pill Ameliorates Alzheimer's Disease-Like Pathology in 3xTg-AD Mice by Targeting Aβ Production, Tau Phosphorylation, Synaptic Loss, and Neuroinflammation.Molecular neurobiology · 2025Article
- Dapagliflozin Ameliorates Doxorubicin-Induced Chemobrain and Cognitive Abnormalities in Rats: Modulation of AKT/GSK-3β and Wnt/β-Catenin Pathways.Neurochemical research · 2025Article
- Radiosynthesis and Evaluation ofACS pharmacology & translational science · 2025Article
- Glucose starvation induces tau phosphorylation leading to cellular stress response in fission yeast.Archives of microbiology · 2025Article
- Oxidative Stress in Huntington's Disease.Biomolecules · 2025Review
- The therapeutic potential of (R)-carvedilol in Huntington's disease through enhancement of autophagy-lysosomal pathway via GSK-3β inhibition.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- Evidence of mutant huntingtin and tau-related pathology within neuronal grafts in Huntington's disease cases.Neurobiology of disease · 2024Article
- NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation.Zoological research · 2024Article
- Design, Synthesis, and Biological Evaluation of Novel Tetrahydroacridin Hybrids with Sulfur-Inserted Linkers as Potential Multitarget Agents for Alzheimer's Disease.Molecules (Basel, Switzerland) · 2024Article
- Review
- Tau Protein Alterations Induced by Hypobaric Hypoxia Exposure.International journal of molecular sciences · 2024Review
- Bioinformatics analysis of the potential receptor and therapeutic drugs for Alzheimer's disease with comorbid Parkinson's disease.Frontiers in aging neuroscience · 2024Article
- Tau: a biomarker of Huntington's disease.Molecular psychiatry · 2023Review
- Activation of Pgk1 Results in Reduced Protein Aggregation in Diverse Neurodegenerative Conditions.Molecular neurobiology · 2023Article
- Selective perforant-pathway atrophy in Huntington disease: MRI analysis of hippocampal subfields.European journal of neurology · 2023Article
- Reduced endothelial caveolin-1 underlies deficits in brain insulin signalling in type 2 diabetes.Brain : a journal of neurology · 2023Article
- Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer's Disease Treatment.International journal of molecular sciences · 2023Article
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific changes in GSK-3β expression may underlie these abnormalities. Thirty-three postmortem hippocampal samples from HD patients (neuropathological grades 2-4) and age- and sex-matched normal control cases were analyzed using real-time quantitative reverse transcription PCRs (qPCRs) and immunohistochemistry. In vitro and in vivo studies looking at hippocampal pathology and GSK-3β were also undertaken in transgenic R6/2 and wild-type mice. We identified a disease and stage-dependent upregulation of GSK-3β mRNA and protein levels in the HD hippocampus, with the active isoform pGSK-3β-Tyr(216) being strongly expressed in dentate gyrus (DG) neurons and astrocytes at a time when phosphorylation of Tau at the AT8 epitope was also present in these same neurons. This upregulation of pGSK-3β-Tyr(216) was also found in the R6/2 hippocampus in vivo and linked to the increased vulnerability of primary hippocampal neurons in vitro. In addition, the increased expression of GSK-3β in the astrocytes of R6/2 mice appeared to be the main driver of Tau phosphorylation and caspase3 activation-induced neuronal death, at least in part via an exacerbated production of major proinflammatory mediators. This stage-dependent overactivation of GSK-3β in HD-affected hippocampal neurons and astrocytes therefore points to GSK-3β as being a critical factor in the pathological development of this condition. As such, therapeutic targeting of this pathway may help ameliorate neuronal dysfunction in HD.
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