ArticleAlzheimer's research & therapy2012
Increased expression of the homologue of enhancer-of-split 1 protects neurons from beta amyloid neurotoxicity and hints at an alternative role for transforming growth factor beta1 as a neuroprotector.
Article in Alzheimer's research & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 21 citations in OpenAlex.
- Aerobic exercise significantly altersJournal of Alzheimer's disease : JAD · 2026Article
- Nerve growth factor: what can surgeons and oncologists learn from a neurological and psychological biomarker?Molecular medicine (Cambridge, Mass.) · 2025Review
- The Microbiota-Gut-Brain Axis in Light of the Brain Axes and Dysbiosis Where Piezo2 Is the Critical Initiating Player.International journal of molecular sciences · 2025Review
- Inflammatory Bridges: Interconnections Between Alzheimer's Disease and Bone Health.Aging and disease · 2025Review
- Cellular Localization and Distribution of TGF-β1, GDNF and PDGF-BB in the Adult Primate Central Nervous System.Neurochemical research · 2023Article
- Cellular response to β-amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics.Animal models and experimental medicine · 2023Review
- The Many Faces of Astrocytes in Alzheimer's Disease.Frontiers in neurology · 2021Review
- The innate immune system and neurogenesis as modulating mechanisms of electroconvulsive therapy in pre-clinical studies.Journal of psychopharmacology (Oxford, England) · 2020Review
- Hes1 expression in mature neurons in the adult mouse brain is required for normal behaviors.Scientific reports · 2019Article
- TGF-β1 Restores Hippocampal Synaptic Plasticity and Memory in Alzheimer Model via the PI3K/Akt/Wnt/β-Catenin Signaling Pathway.Journal of molecular neuroscience : MN · 2019Article
- TGF-β1/Smad3 Signaling Pathway Suppresses Cell Apoptosis in Cerebral Ischemic Stroke Rats.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Hes1: the maestro in neurogenesis.Cellular and molecular life sciences : CMLS · 2016Review
- Signaling pathways regulating neuron-glia interaction and their implications in Alzheimer's disease.Journal of neurochemistry · 2016Review
- Hes-1 SUMOylation by protein inhibitor of activated STAT1 enhances the suppressing effect of Hes-1 on GADD45α expression to increase cell survival.Journal of biomedical science · 2014Article
- Neuronal and astroglial TGFβ-Smad3 signaling pathways differentially regulate dendrite growth and synaptogenesis.Neuromolecular medicine · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAlzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid (Aβ) in the brain, which produces progressive neuronal loss and dementia. We recently demonstrated that the noxious effects of Aβ on cultured hippocampal neurons are in part provoked by the antagonism of nerve growth factor (NGF) signalling, which impairs the activation of nuclear factor κB (NF-κB) by impeding the tyrosine phosphorylation of I-κBα. As a result, the expression of the homologue of Enhancer-of split 1 (Hes1) gene is downregulated and ultimately, gamma-aminobutyric acid (GABA)-ergic connectivity is lost.
methodsHes1 activity was promoted in cultured hippocampal neurons by overexpressing a Hes1-encoding plasmid or by upregulating this gene by activating NF-κB through different approaches (overexpressing either the I-κB kinaseβ, or p65/RelA/NF-κB). Alternatively neurons were exposed to TGFβ1. Dendrite patterning, GABAergic connectivity and cell survival were analyzed by immunofluorescence microscopy. Hes1 expression was determined by real-time PCR. NF-κB activation was measured using the dual-luciferase reporter assay.
resultsThe expression of Hes1 abolished the effects of Aβ on dendritic patterning and GABAergic input, and it prevented the death of the cultured neurons. TGFβ1, a known neuroprotector, could counteract the deleterious effects of Aβ by inducing NF-κB activation following the serine phosphorylation of I-κBα. Indeed, the number of GABAergic terminals generated by inducing Hes1 expression was doubled.
conclusionOur data define some of the mechanisms involved in Aβ-mediated cell death and they point to potential means to counteract this noxious activity.
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.