ArticleiScience2021
Isoform-selective decrease of glycogen synthase kinase-3-beta (GSK-3β) reduces synaptic tau phosphorylation, transcellular spreading, and aggregation.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- Current Landscape of Glycogen Synthase Kinase-3β PET Tracers: Progress, Limitations, and Perspectives-A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- NanoBiT screening identifies the azaoxafluorene VT11 as potent tau interaction inhibitor.Scientific reports · 2026Article
- Intervening in aging and related diseases with gene therapy techniques.Cell reports. Medicine · 2026Review
- Neuroinflammation and Tauopathies.Molecular biology reports · 2026Review
- IgLON5 autoimmune antibodies activate Tau via neuronal hyperactivity.Science advances · 2026Article
- PROTAC-mediated multi-target protein degradation in Alzheimer's disease: mechanistic insights, therapeutic applications, and translational challenges.RSC medicinal chemistry · 2026Review
- Reimagining GSK-3β Therapeutics in Alzheimer's Disease: From Inhibition to Activity Normalization and Targeted Degradation.Journal of molecular neuroscience : MN · 2026Review
- Reticulocalbin-2 in the Hippocampus Improves Cognitive Function of Diabetic Mice.Brain and behavior · 2026Article
- Rational design of k-casein peptides to modulate GSK-3B dynamics for Alzheimer's therapy.Scientific reports · 2026Article
- Glycogen synthase kinase-3 activation and dysregulation of amyloid transport receptors expression and shedding in HIV-induced Alzheimer's disease-like pathology: modulatory effects of CCR5 antagonists.Acta neuropathologica communications · 2025Article
- Evaluation of [ACS chemical neuroscience · 2025Article
- Therapeutic potential of melatonin-induced mitophagy in the pathogenesis of Alzheimer's disease.Inflammopharmacology · 2025Review
- Decoding the Role of Neurotrophins in Glycogen Synthase Kinase 3-Beta Regulation in Alzheimer's Disease.Molecular neurobiology · 2025Review
- Limettin and PD98059 Mitigated Alzheimer's Disease Like Pathology Induced by Streptozotocin in Mouse Model: Role of p-ERK1/2/p-GSK-3β/p-CREB/BDNF Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Identification of AS1842856 as a novel small-molecule GSK3α/β inhibitor against Tauopathy by accelerating GSK3α/β exocytosis.Aging cell · 2025Article
- Increased expression of plasma mir-9-3p and let-7b-3p in methamphetamine use disorder and its clinical significance.Scientific reports · 2024Article
- GSK3β phosphorylation catalyzes the aggregation of tau into Alzheimer's disease-like filaments.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Drosophila model for mechanistic investigation of tau protein spread.Disease models & mechanisms · 2024Article
- Endogenous tau released from humanbioRxiv : the preprint server for biology · 2024Article
- Mitochondria in Alzheimer's Disease Pathogenesis.Life (Basel, Switzerland) · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been suggested that aberrant activation of glycogen synthase kinase-3-beta (GSK-3β) can trigger abnormal tau hyperphosphorylation and aggregation, which ultimately leads to neuronal/synaptic damage and impaired cognition in Alzheimer disease (AD). We examined if isoform-selective partial reduction of GSK-3β can decrease pathological tau changes, including hyperphosphorylation, aggregation, and spreading, in mice with localized human wild-type tau (hTau) expression in the brain. We used adeno-associated viruses (AAVs) to express hTau locally in the entorhinal cortex of wild-type and GSK-3β hemi-knockout (GSK-3β-HK) mice. GSK-3β-HK mice had significantly less accumulation of hyperphosphorylated tau in synapses and showed a significant decrease of tau protein spread between neurons. In primary neuronal cultures from GSK-3β-HK mice, the aggregation of exogenous FTD-mutant tau was also significantly reduced. These results show that a partial decrease of GSK-3β significantly represses tau-initiated neurodegenerative changes in the brain, and therefore is a promising therapeutic target for AD and other tauopathies.
Indexed as
Identifiers
What OpenQuestion holds
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.