ReviewJournal of Alzheimer's disease : JAD2012
Triangulated mal-signaling in Alzheimer's disease: roles of neurotoxic ceramides, ER stress, and insulin resistance reviewed.
Review in Journal of Alzheimer's disease : JAD, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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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
61 citing papers in PubMed, 103 citations in OpenAlex.
- Insulin Resistance and Blood Pressure Control on Cognitive Outcomes.Hypertension (Dallas, Tex. : 1979) · 2026Trial
- Adipose Tissue-Central Nervous System Axis in Obesity: Molecular Mechanisms, Inflammation, and Nutritional and Technological Implications.Metabolites · 2026Review
- Rethinking on bile acid-brain axis: decoding neurotoxic and neuroprotective landscape in aging and Alzheimer's disease.Biogerontology · 2026Review
- Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline.Diseases (Basel, Switzerland) · 2025Review
- Deciphering the Role of Different Ceramide Synthases in the Human Cardiomyocyte Hypertrophic Response.Metabolites · 2025Article
- Selective Knockdown of Ceramide Synthases Reveals Opposite Roles of Different Ceramide Species in Cardiac Homeostasis.Metabolites · 2025Article
- Ablation of Hepatic Asah1 Gene Disrupts Hepatic Lipid Homeostasis and Promotes Fibrotic Nonalcoholic Steatohepatitis in Mice.The American journal of pathology · 2025Article
- Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Alpha-synuclein aggregation induces prominent cellular lipid changes as revealed by Raman spectroscopy and machine learning analysis.Brain communications · 2025Article
- Spinal cord injury-induced metabolic impairment and steatohepatitis develops in non-obese rats and is exacerbated by premorbid obesity.Experimental neurology · 2024Article
- Transcriptomic profiling of sciatic nerves and dorsal root ganglia reveals site-specific effects of prediabetic neuropathy.Translational research : the journal of laboratory and clinical medicine · 2024Article
- Novel Insights into Psychosis and Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes.International journal of molecular sciences · 2024Review
- The Metabolic and Lipidomic Fingerprint of Torin1 Exposure in Mouse Embryonic Fibroblasts Using Untargeted Metabolomics.Metabolites · 2024Article
- PCDHA9 as a candidate gene for amyotrophic lateral sclerosis.Nature communications · 2024Article
- ReTimeML: a retention time predictor that supports the LC-MS/MS analysis of sphingolipids.Scientific reports · 2024Article
- Early-Stage Moderate Alcohol Feeding Dysregulates Insulin-Related Metabolic Hormone Expression in the Brain: Potential Links to Neurodegeneration Including Alzheimer's Disease.Journal of Alzheimer's disease reports · 2024Article
- Dysregulated mTOR networks in experimental sporadic Alzheimer's disease.Frontiers in cellular neuroscience · 2024Article
- A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer's disease, and their co-morbidities.Frontiers in pharmacology · 2024Review
- Aerobic exercise combined with memory strategy training improve the cognitive function.Brain and behavior · 2023Article
- Malignant Brain Aging: The Formidable Link Between Dysregulated Signaling Through Mechanistic Target of Rapamycin Pathways and Alzheimer's Disease (Type 3 Diabetes).Journal of Alzheimer's disease : JAD · 2023Review
1 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
1 author at 1 institution in 1 country.
Funding
Abstract
Ceramides are lipid signaling molecules that cause cytotoxicity and cell death mediated by insulin resistance, inflammation, and endoplasmic reticulum (ER) stress. However, insulin resistance dysregulates lipid metabolism, which promotes ceramide accumulation with attendant inflammation and ER stress. Herein, we discuss two major pathways, extrinsic and intrinsic, that converge and often overlap in propagating AD-type neurodegeneration via a triangulated mal-signaling network. First, we review evidence that systemic insulin resistance diseases linked to obesity, type 2 diabetes, and non-alcoholic steatohepatitis promote neurodegeneration. Mechanistically, we propose that toxic ceramides generated in extra-CNS tissues (e.g., liver) get released into peripheral blood, and subsequently transit across the blood-brain barrier into the brain where they induce brain insulin resistance, inflammation, and cell death (extrinsic pathway). Then we discuss the role of the intrinsic pathway of neurodegeneration which is mediated by endogenous or primary brain insulin/IGF resistance, and impairs neuronal and oligodendrocyte survival, energy metabolism, membrane integrity, cytoskeletal function, and AβPP-Aβ secretion. The end result is increased ER stress and ceramide generation, which exacerbate brain insulin resistance, cell death, myelin degeneration, and neuroinflammation. Altogether, the data suggest that the triangulated mal-signaling network mediated by toxic ceramides, ER stress, and insulin resistance should be targeted to disrupt positive feedback loops that drive the AD neurodegeneration cascade.
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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.