ArticleMolecular psychiatry2009
Amyloid-beta causes memory impairment by disturbing the JAK2/STAT3 axis in hippocampal neurons.
Article in Molecular psychiatry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 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
105 citing papers in PubMed, 206 citations in OpenAlex.
- Activation of M1mAChR's improves spatial learning and memory deficits in rats exposed to chronic intermittent hypoxia.Scientific reports · 2026Article
- The mRNA Expression Levels of General Transcription Factors Altered in Alzheimer Cases Possibly Due to Amyloid Beta 1-42 Exposure.Noro psikiyatri arsivi · 2026Article
- Epidermal growth factor receptor modulation for neural repair: Implications for neurodegenerative disease therapy.Frontiers in molecular neuroscience · 2026Review
- JAK Inhibitors and Memory Impairment: Disproportionality Analyses in the WHO Global Pharmacovigilance Database, VigiBase.Fundamental & clinical pharmacology · 2026Article
- ROS-Driven STAT1 S-Glutathionylation Sustains IFNγ Signaling and Pro-Inflammatory Microglial Polarization.Antioxidants (Basel, Switzerland) · 2025Article
- Irisin: Emerging Therapeutic Targets for Cognitive Impairment-Related Diseases.Expert reviews in molecular medicine · 2025Review
- Neurological Adverse Events Associated with the Use of Janus Kinase Inhibitors: A Pharmacovigilance Study Based on Vigibase.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Ruxolitinib-dependent reduction of seizure load and duration is accompanied by spatial memory improvement in the rat pilocarpine model of temporal lobe epilepsy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Modulating Neuroinflammation as a Prospective Therapeutic Target in Alzheimer's Disease.Cells · 2025Review
- Novel insights into the ROCK-JAK-STAT signaling pathway in upper respiratory tract infections and neurodegenerative diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Intranasal administration ofFrontiers in pharmacology · 2025Article
- Exercise training exerts beneficial effects on Alzheimer's disease through multiple signaling pathways.Frontiers in aging neuroscience · 2025Review
- STAT3 ameliorates truncated tau-induced cognitive deficits.Neural regeneration research · 2024Article
- Comorbidity Genes of Alzheimer's Disease and Type 2 Diabetes Associated with Memory and Cognitive Function.International journal of molecular sciences · 2024Review
- JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.Molecular biomedicine · 2023Review
- The Role of the JAK/STAT Signaling Pathway in the Pathogenesis of Alzheimer's Disease: New Potential Treatment Target.International journal of molecular sciences · 2023Review
- The JAK-STAT Signaling Pathway in Epilepsy.Current neuropharmacology · 2023Review
- Vision transformers for the prediction of mild cognitive impairment to Alzheimer's disease progression using mid-sagittal sMRI.Frontiers in aging neuroscience · 2023Article
- Incretin Mimetics Restore the ER-Mitochondrial Axis and Switch Cell Fate Towards Survival in LUHMES Dopaminergic-Like Neurons: Implications for Novel Therapeutic Strategies in Parkinson's Disease.Journal of Parkinson's disease · 2023Article
- Alzheimer's disease and neuroinflammation: will new drugs in clinical trials pave the way to a multi-target therapy?Frontiers in pharmacology · 2023Review
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elevation of intracranial soluble amyloid-beta (Abeta) levels has been implicated in the pathogenesis of Alzheimer's disease (AD). Intracellular events in neurons, which lead to memory loss in AD, however, remain elusive. Humanin (HN) is a short neuroprotective peptide abolishing Abeta neurotoxicity. Recently, we found that HN derivatives activate the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling axis. We here report that an HN derivative named colivelin completely restored cognitive function in an AD model (Tg2576) by activating the JAK2/STAT3 axis. In accordance, immunofluorescence staining using a specific antibody against phospho- (p-) STAT3 revealed that p-STAT3 levels in hippocampal neurons age-dependently decreased in both AD model mice and AD patients. Intracerebroventricular administration of Abeta1-42 downregulated p-STAT3 whereas passive immunization with anti-Abeta antibody conversely restored hippocampal p-STAT3 levels in Tg2576 mice, paralleling the decrease in the brain Abeta burden. Abeta1-42 consistently modulated p-STAT3 levels in primary neurons. Pharmacological inhibition of the JAK2/STAT3 axis not only induced significant loss of spatial working memory by downregulating an acetylcholine-producing enzyme choline acetyltransferase but also desensitized the M(1)-type muscarinic acetylcholine receptor. Thus, we propose a novel theory accounting for memory impairment related to AD: Abeta-dependent inactivation of the JAK2/STAT3 axis causes memory loss through cholinergic dysfunction. Our findings provide not only a novel pathological hallmark in AD but also a novel target in AD therapy.
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.