ArticleThe Journal of biological chemistry2009
Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric a{beta}.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 159 citations in OpenAlex.
- Alcohol addiction and Alzheimer's disease: a molecular collision course.Translational psychiatry · 2025Review
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Human Glucose Transporters in Health and Selected Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Understanding the Intersection Between Hormonal Dynamics and Brain Plasticity in Alzheimer's Disease: A Narrative Review for Implementing New Therapeutic Strategies.Health science reports · 2025Review
- The role of branched chain aminotransferase in the interrelated pathways of type 2 diabetes mellitus and Alzheimer's disease.Journal of diabetes and metabolic disorders · 2025Review
- Insulin resistance in Alzheimer's disease: signalling mechanisms and therapeutics strategies.Inflammopharmacology · 2025Review
- Associations Between Diabetes Mellitus and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- BACE1 at the crossroads of a vicious circle between Alzheimer's disease and diabetes mellitus.Frontiers in dementia · 2025Review
- Dysregulation of energy metabolism in Alzheimer's disease.Journal of neurology · 2024Review
- Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting.Pharmacological reviews · 2024Review
- Comparing regional brain uptake of incretin receptor agonists after intranasal delivery in CD-1 mice and the APP/PS1 mouse model of Alzheimer's disease.Alzheimer's research & therapy · 2024Article
- Association of triglyceride glucose-body mass index with Alzheimer's disease pathology, cognition and brain structure in non-demented people.Scientific reports · 2024Article
- Research Progress on the Pathogenesis, Diagnosis, and Drug Therapy of Alzheimer's Disease.Brain sciences · 2024Review
- Insulin Signaling Differentially Regulates the Trafficking of Insulin and Amyloid Beta Peptides at the Blood-Brain Barrier.Molecular pharmaceutics · 2024Article
- Assessing interstitial fluid dynamics in type 2 diabetes mellitus and prediabetes cases through diffusion tensor imaging analysis along the perivascular space.Frontiers in aging neuroscience · 2024Article
- GLP-1 Analogs, SGLT-2, and DPP-4 Inhibitors: A Triad of Hope for Alzheimer's Disease Therapy.Biomedicines · 2023Review
- Triglyceride-glucose index as a valuable predictor for aged 65-years and above in critical delirium patients: evidence from a multi-center study.BMC geriatrics · 2023Article
- Anti-Amyloid Immunotherapies for Alzheimer's Disease: A 2023 Clinical Update.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- A Pathophysiological Intersection of Diabetes and Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Dysfunctional Glucose Metabolism in Alzheimer's Disease Onset and Potential Pharmacological Interventions.International journal of molecular sciences · 2022Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Accumulation of amyloid beta (Abeta) oligomers in the brain is toxic to synapses and may play an important role in memory loss in Alzheimer disease. However, how these toxins are built up in the brain is not understood. In this study we investigate whether impairments of insulin and insulin-like growth factor-1 (IGF-1) receptors play a role in aggregation of Abeta. Using primary neuronal culture and immortal cell line models, we show that expression of normal insulin or IGF-1 receptors confers cells with abilities to reduce exogenously applied Abeta oligomers (also known as ADDLs) to monomers. In contrast, transfection of malfunctioning human insulin receptor mutants, identified originally from patient with insulin resistance syndrome, or inhibition of insulin and IGF-1 receptors via pharmacological reagents increases ADDL levels by exacerbating their aggregation. In healthy cells, activation of insulin and IGF-1 receptor reduces the extracellular ADDLs applied to cells via seemingly the insulin-degrading enzyme activity. Although insulin triggers ADDL internalization, IGF-1 appears to keep ADDLs on the cell surface. Nevertheless, both insulin and IGF-1 reduce ADDL binding, protect synapses from ADDL synaptotoxic effects, and prevent the ADDL-induced surface insulin receptor loss. Our results suggest that dysfunctions of brain insulin and IGF-1 receptors contribute to Abeta aggregation and subsequent synaptic loss.
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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.