ArticleACS chemical neuroscience2016
Direct High Affinity Interaction between Aβ42 and GSK3α Stimulates Hyperphosphorylation of Tau. A New Molecular Link in Alzheimer's Disease?
Article in ACS chemical neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
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- PROTAC-mediated multi-target protein degradation in Alzheimer's disease: mechanistic insights, therapeutic applications, and translational challenges.RSC medicinal chemistry · 2026Review
- Design and synthesis of new phosphazine and triazole derivatives for treatment of Alzheimer's disease: modulating ROS/JNK and Wnt/β-catenin signaling pathways.RSC advances · 2026Article
- HIV-1 Tat and gp120 as key drivers of neurodegeneration in the central nervous system.Frontiers in microbiology · 2026Review
- Review
- The efficacy and pharmacological mechanism of Guilingji to prevent Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- GSK3α negatively regulates GSK3β by decreasing its protein levels and enzymatic activity in mouse embryonic stem cells.Stem cell reports · 2025Article
- Probe-dependent Proximity Profiling (ProPPr) Uncovers Similarities and Differences in Phospho-Tau-Associated Proteomes Between Tauopathies.Molecular neurodegeneration · 2025Article
- Identification of AS1842856 as a novel small-molecule GSK3α/β inhibitor against Tauopathy by accelerating GSK3α/β exocytosis.Aging cell · 2025Article
- Hirschsprung's disease: m6A methylase VIRMA suppresses cell migration and proliferation by regulating GSK3β.Pediatric research · 2024Article
- Understanding Glycogen Synthase Kinase-3: A Novel Avenue for Alzheimer's Disease.Molecular neurobiology · 2024Review
- GSK3: A potential target and pending issues for treatment of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Review
- Hexa-Histidine, a Peptide with Versatile Applications in the Study of Amyloid-β(1-42) Molecular Mechanisms of Action.Molecules (Basel, Switzerland) · 2023Article
- Brain Hydrophobic Peptides Antagonists of Neurotoxic Amyloid β Peptide Monomers/Oligomers-Protein Interactions.International journal of molecular sciences · 2023Review
- Computational Studies Applied to Linalool and Citronellal Derivatives Against Alzheimer's and Parkinson's Disorders: A Review with Experimental Approach.Current neuropharmacology · 2023Review
- Design and Experimental Evaluation of a Peptide Antagonist against Amyloid β(1-42) Interactions with Calmodulin and Calbindin-D28k.International journal of molecular sciences · 2022Article
- A Palette of Fluorescent AInternational journal of molecular sciences · 2022Article
- Novel Stilbene-Nitroxyl Hybrid Compounds Display Discrete Modulation of Amyloid Beta Toxicity and Structure.Frontiers in chemistry · 2022Article
- The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Expression of N-Terminal Cysteine AβBiochemistry · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Amyloid β peptide (Aβ42) assemblies are considered central to the development of Alzheimer's disease, but the mechanism of this toxicity remains unresolved. We screened protein microarrays with on-pathway oligomeric Aβ42 to identify candidate proteins interacting with toxic Aβ42 species. Samples prepared from Alexa546-Aβ42 and Aβ42 monomers at 1:5 molar ratio were incubated with the array during a time window of the amyloid fibril formation reaction during which the maximum number of transient oligomers exist in the reaction flux. A specific interaction was detected between Aβ42 and glycogen synthase kinase 3α (GSK3α), a kinase previously implicated in the disease pathology. This interaction was validated with anti-GSK3α immunoprecipitation assays in neuronal cell lysates. Confocal microscopy studies further identified colocalization of Aβ42 and GSK3α in neurites of mature primary mouse neurons. A high binding affinity (KD = 1 nM) was measured between Alexa488-Aβ42 and GSK3α in solution using thermophoresis. An even lower apparent KD was estimated between GSK3α and dextran-immobilized Aβ42 in surface plasmon resonance experiments. Parallel experiments with GSK3β also identified colocalization and high affinity binding to this isoform. GSK3α-mediated hyperphosphorylation of the protein tau was found to be stimulated by Aβ42 in in vitro phosphorylation assays and identified a functional relationship between the proteins. We uncover a direct and functional molecular link between Aβ42 and GSK3α, which opens an important avenue toward understanding the mechanism of Aβ42-mediated neuronal toxicity in Alzheimer's disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.