ArticleMolecular biology of the cell2017
Neuroprotective astrocyte-derived insulin/insulin-like growth factor 1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers.
Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 85 citations in OpenAlex.
- Safety, Efficacy, and Feasibility of Intranasal Insulin for the Treatment of Mild Cognitive Impairment and Alzheimer Disease Dementia: A Randomized Clinical Trial.JAMA neurology · 2020 · on this mapTrial
- Back Again to the Future: A New Era for Cerebroprotection.Annals of neurology · 2026Review
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Article
- Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting.Pharmacological reviews · 2024Review
- Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease.Journal of neurochemistry · 2024Review
- A brain-derived insulin signal encodes protein satiety for nutrient-specific feeding inhibition.Cell reports · 2024Article
- The metabolic effects of resumption of a high fat diet after weight loss are sex dependent in mice.Scientific reports · 2023Article
- Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice.Journal of molecular neuroscience : MN · 2023Article
- Actions and Consequences of Insulin in the Striatum.Biomolecules · 2023Review
- Ketogenic Diet Modulates Neuroinflammation via Metabolites from Lactobacillus reuteri After Repetitive Mild Traumatic Brain Injury in Adolescent Mice.Cellular and molecular neurobiology · 2023Article
- The Potential Roles of Exosomes Carrying APP and Tau Cleavage Products in Alzheimer's Disease.Journal of clinical medicine · 2023Review
- Metabolic Syndrome as a Risk Factor for Alzheimer's Disease: A Focus on Insulin Resistance.International journal of molecular sciences · 2023Review
- Effect of insulin and cinnamon extract on spatial memory and gene expression of GLUT1, 3, and 4 in streptozotocin-induced Alzheimer's model in rats.Iranian journal of basic medical sciences · 2023Article
- The Role of Insulin Signaling in Hippocampal-Related Diseases: A Focus on Alzheimer's Disease.International journal of molecular sciences · 2022Review
- The role of astrocytes in prion-like mechanisms of neurodegeneration.Brain : a journal of neurology · 2022Review
- Dysmetabolism and Neurodegeneration: Trick or Treat?Nutrients · 2022Review
- Diabetes mellitus and Parkinson's disease: dangerous liaisons between insulin and dopamine.Neural regeneration research · 2022Review
- Potential role of IGF-1/GLP-1 signaling activation in intracerebral hemorrhage.Current research in neurobiology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
Abstract
Synaptopathy underlying memory deficits in Alzheimer's disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptide (AβOs). Given the long latency and incomplete penetrance of AD dementia with respect to Aβ pathology, we hypothesized that factors present in the CNS may physiologically protect neurons from the deleterious impact of AβOs. Here we employed physically separated neuron-astrocyte cocultures to investigate potential non-cell autonomous neuroprotective factors influencing AβO toxicity. Neurons cultivated in the absence of an astrocyte feeder layer showed abundant AβO binding to dendritic processes and associated synapse deterioration. In contrast, neurons in the presence of astrocytes showed markedly reduced AβO binding and synaptopathy. Results identified the protective factors released by astrocytes as insulin and insulin-like growth factor-1 (IGF1). The protective mechanism involved release of newly bound AβOs into the extracellular medium dependent upon trafficking that was sensitive to exosome pathway inhibitors. Delaying insulin treatment led to AβO binding that was no longer releasable. The neuroprotective potential of astrocytes was itself sensitive to chronic AβO exposure, which reduced insulin/IGF1 expression. Our findings support the idea that physiological protection against synaptotoxic AβOs can be mediated by astrocyte-derived insulin/IGF1, but that this protection itself is vulnerable to AβO buildup.
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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.