ArticleThe EMBO journal2023
Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer's disease.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 33 citations in OpenAlex.
- Neutrophil-mediated BDNF delivery for the treatment of moderate to severe Alzheimer's disease.Acta pharmaceutica Sinica. B · 2026Article
- Maintaining and regaining episodic memory in Alzheimer disease: a circuit-based perspective.Nature reviews. Neurology · 2026Review
- High-Fat Diet and a High Amyloid Load Interact to Induce PKC-α Dependent Synaptic Insulin Resistance.Molecular & cellular proteomics : MCP · 2026Article
- Recognition of the CREB-Binding Protein/Mixed Lineage Leukemia Interface by Sulfonyl-γ-AApeptides: Beyond Mimicry of Mixed Lineage Leukemia.Journal of medicinal chemistry · 2025Article
- Current methods in explainable artificial intelligence and future prospects for integrative physiology.Pflugers Archiv : European journal of physiology · 2025Review
- Innovations in Alzheimer's disease diagnostic technologies: clinical prospects of novel biomarkers, multimodal integration, and non-invasive detection.Frontiers in neurology · 2025Review
- Dual Role of NMDAR Containing NR2A and NR2B Subunits in Alzheimer's Disease.International journal of molecular sciences · 2024Article
- MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration.Science advances · 2023Article
- Excitation-transcription coupling, neuronal gene expression and synaptic plasticity.Nature reviews. Neuroscience · 2023Review
- Integration of nuclear CaCellular and molecular life sciences : CMLS · 2023Article
- Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer's disease.The EMBO journal · 2023Article
- A Jacob/nsmf gene knockout does not protect against acute hypoxia- and NMDA-induced excitotoxic cell death.Molecular brain · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
Abstract
Synaptic dysfunction caused by soluble β-amyloid peptide (Aβ) is a hallmark of early-stage Alzheimer's disease (AD), and is tightly linked to cognitive decline. By yet unknown mechanisms, Aβ suppresses the transcriptional activity of cAMP-responsive element-binding protein (CREB), a master regulator of cell survival and plasticity-related gene expression. Here, we report that Aβ elicits nucleocytoplasmic trafficking of Jacob, a protein that connects a NMDA-receptor-derived signalosome to CREB, in AD patient brains and mouse hippocampal neurons. Aβ-regulated trafficking of Jacob induces transcriptional inactivation of CREB leading to impairment and loss of synapses in mouse models of AD. The small chemical compound Nitarsone selectively hinders the assembly of a Jacob/LIM-only 4 (LMO4)/ Protein phosphatase 1 (PP1) signalosome and thereby restores CREB transcriptional activity. Nitarsone prevents impairment of synaptic plasticity as well as cognitive decline in mouse models of AD. Collectively, the data suggest targeting Jacob protein-induced CREB shutoff as a therapeutic avenue against early synaptic dysfunction in AD.
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.