ArticleTranslational neurodegeneration2022
Neddylation-dependent protein degradation is a nexus between synaptic insulin resistance, neuroinflammation and Alzheimer's disease.
Article in Translational neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 22 citations in OpenAlex.
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Neddylation-dependent CUL3-KLHL12 E3 ligase drives microglial oxidative stress and neuroinflammation in traumatic brain injury by targeting GCLM for degradation.Journal of translational medicine · 2026Article
- Early, sex-dependent and progressive proteomic imbalance in the amygdala during Alzheimer´s disease continuum.Biology of sex differences · 2026Article
- High-Fat Diet and a High Amyloid Load Interact to Induce PKC-α Dependent Synaptic Insulin Resistance.Molecular & cellular proteomics : MCP · 2026Article
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- Microglia-Mediated Neuroinflammation Through Phosphatidylinositol 3-Kinase Signaling Causes Cognitive Dysfunction.International journal of molecular sciences · 2025Review
- Neddylation modification stabilizes LC3B by antagonizing its ubiquitin-mediated degradation and promoting autophagy in skin.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exploring the role of insulin resistance in bridging the metabolic syndrome and Alzheimer's disease-a review of mechanistic studies.Frontiers in endocrinology · 2025Review
- Neddylation steers the fate of cellular receptors.Experimental & molecular medicine · 2024Review
- Transcriptomic Profile of Mouse Brain Ageing in Early Developmental Stages.Brain sciences · 2024Article
- [Sequencing Analysis of miRNAs in Brain-Derived Exosomes of Adolescent Mice With Depression-Like Behaviors].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Article
- The Strategies for Treating "Alzheimer's Disease": Insulin Signaling May Be a Feasible Target.Current issues in molecular biology · 2022Review
- Role of Neddylation in Neurodegenerative Diseases.NeuroSci · 2022Review
- Brain insulin resistance and the therapeutic value of insulin and insulin-sensitizing drugs in Alzheimer's disease neuropathology.Acta neurologica Belgica · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe metabolic syndrome is a consequence of modern lifestyle that causes synaptic insulin resistance and cognitive deficits and that in interaction with a high amyloid load is an important risk factor for Alzheimer's disease. It has been proposed that neuroinflammation might be an intervening variable, but the underlying mechanisms are currently unknown.
methodsWe utilized primary neurons to induce synaptic insulin resistance as well as a mouse model of high-risk aging that includes a high amyloid load, neuroinflammation, and diet-induced obesity to test hypotheses on underlying mechanisms.
resultsWe found that neddylation and subsequent activation of cullin-RING ligase complexes induced synaptic insulin resistance through ubiquitylation and degradation of the insulin-receptor substrate IRS1 that organizes synaptic insulin signaling. Accordingly, inhibition of neddylation preserved synaptic insulin signaling and rescued memory deficits in mice with a high amyloid load, which were fed with a 'western diet'.
conclusionsCollectively, the data suggest that neddylation and degradation of the insulin-receptor substrate is a nodal point that links high amyloid load, neuroinflammation, and synaptic insulin resistance to cognitive decline and impaired synaptic plasticity in high-risk aging.
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.