ArticleThe Journal of biological chemistry2015
Effect of cholesterol reduction on receptor signaling in neurons.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- Regulation of Neuronal Senescence byBiology · 2026Article
- TLR4-Mediated Immune Dysfunction Links MASLD and Parkinson's Disease: Insights from an Omics-Based Network Analysis.NeuroSci · 2026Article
- Natural products as HMG-CoA reductase inhibitors (statins) for the management of non-communicable diseases.Inflammopharmacology · 2026Review
- Beta cells to brain cells: The pivotal role of insulin and glucose metabolism in Alzheimer's disease.Neuroprotection (Chichester, England) · 2025Review
- Streptozotocin and L-Buthionine-Sulfoximine Decrease Neuron Membrane Lipid Packing and Alter Insulin Signaling.Neurotoxicity research · 2025Article
- Article
- Down-regulation of AKT proteins slows the growth of mutant-KRAS pancreatic tumors.bioRxiv : the preprint server for biology · 2024Article
- The effects of cholesterol and statins on Parkinson's neuropathology: a narrative review.Inflammopharmacology · 2024Review
- Role of lipids in the control of autophagy and primary cilium signaling in neurons.Neural regeneration research · 2024Review
- Neuro-HIV-New insights into pathogenesis and emerging therapeutic targets.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Pros and cons for statins use and risk of Parkinson's disease: An updated perspective.Pharmacology research & perspectives · 2023Review
- Long Non-Coding RNA TUG1 Attenuates Insulin Resistance in Mice with Gestational Diabetes Mellitus via Regulation of the MicroRNA-328-3p/SREBP-2/ERK Axis.Diabetes & metabolism journal · 2023Article
- Cholesterol Management in Neurology: Time for Revised Strategies?Journal of personalized medicine · 2022Review
- Region-Specific Characteristics of Astrocytes and Microglia: A Possible Involvement in Aging and Diseases.Cells · 2022Review
- Microarray profiling of hypothalamic gene expression changes in Huntington's disease mouse models.Frontiers in neuroscience · 2022Article
- Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer's disease.Frontiers in molecular neuroscience · 2022Review
- Inverted U-shaped correlation between serum low-density lipoprotein cholesterol levels and cognitive functions of patients with type 2 diabetes mellitus.Lipids in health and disease · 2021Article
- Cognition, Statins, and Cholesterol in Elderly Ischemic Stroke Patients: A Neurologist's Perspective.Medicina (Kaunas, Lithuania) · 2021Article
- Membrane Cholesterol Is a Critical Determinant for Hippocampal Neuronal Polarity.Frontiers in molecular neuroscience · 2021Article
- Striatal infusion of cholesterol promotes dose-dependent behavioral benefits and exerts disease-modifying effects in Huntington's disease mice.EMBO molecular medicine · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Diabetes mellitus is associated with a variety of complications, including alterations in the central nervous system (CNS). We have recently shown that diabetes results in a reduction of cholesterol synthesis in the brain due to decreased insulin stimulation of SREBP2-mediated cholesterol synthesis in neuronal and glial cells. In the present study, we explored the effects of the decrease in cholesterol on neuronal cell function using GT1-7 hypothalamic cells subjected to cholesterol depletion in vitro using three independent methods: 1) exposure to methyl-β-cyclodextrin, 2) treatment with the HMG-CoA reductase inhibitor simvastatin, and 3) shRNA-mediated knockdown of SREBP2. All three methods produced 20-31% reductions in cellular cholesterol content, similar to the decrease in cholesterol synthesis observed in diabetes. All cholesterol-depleted neuron-derived cells, independent of the method of reduction, exhibited decreased phosphorylation/activation of IRS-1 and AKT following stimulation by insulin, insulin-like growth factor-1, or the neurotrophins (NGF and BDNF). ERK phosphorylation/activation was also decreased after methyl-β-cyclodextrin and statin treatment but increased in cells following SREBP2 knockdown. In addition, apoptosis in the presence of amyloid-β was increased. Reduction in cellular cholesterol also resulted in increased basal autophagy and impairment of induction of autophagy by glucose deprivation. Together, these data indicate that a reduction in neuron-derived cholesterol content, similar to that observed in diabetic brain, creates a state of insulin and growth factor resistance that could contribute to CNS-related complications of diabetes, including increased risk of neurodegenerative diseases, such as Alzheimer disease.
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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.