ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Increased membrane cholesterol might render mature hippocampal neurons more susceptible to beta-amyloid-induced calpain activation and tau toxicity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Calpain Inhibitors as Potential Therapeutic Modulators in Neurodegenerative Diseases.Neurochemical research · 2022Pooled it
- Regulation of Neuronal Senescence byBiology · 2026Article
- Neuronal γ-secretase regulates lipid metabolism, linking cholesterol to synaptic dysfunction in Alzheimer's disease.Neuron · 2023Article
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- The Sigma Receptors in Alzheimer's Disease: New Potential Targets for Diagnosis and Therapy.International journal of molecular sciences · 2023Review
- The Antifungal Antibiotic Filipin as a Diagnostic Tool of Cholesterol Alterations in Lysosomal Storage Diseases and Neurodegenerative Disorders.Antibiotics (Basel, Switzerland) · 2023Review
- Aβ and Tau Interact with Metal Ions, Lipid Membranes and Peptide-Based Amyloid Inhibitors: Are These Common Features Relevant in Alzheimer's Disease?Molecules (Basel, Switzerland) · 2022Review
- Free Cholesterol Accelerates Aβ Self-Assembly on Membranes at Physiological Concentration.International journal of molecular sciences · 2022Article
- Implications of High-Density Cholesterol Metabolism for Oocyte Biology and Female Fertility.Frontiers in cell and developmental biology · 2022Review
- Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer's disease.Frontiers in molecular neuroscience · 2022Review
- The formation of small aggregates contributes to the neurotoxic effects of tauNeurochemistry international · 2022Article
- Misregulation of Wnt Signaling Pathways at the Plasma Membrane in Brain and Metabolic Diseases.Membranes · 2021Review
- Role of the Lipid Membrane and Membrane Proteins in Tau Pathology.Frontiers in cell and developmental biology · 2021Review
- Melatonin Alters Fluid Phase Coexistence in POPC/DPPC/Cholesterol Membranes.Biophysical journal · 2020Article
- Sigma-2 Receptor-A Potential Target for Cancer/Alzheimer's Disease Treatment via Its Regulation of Cholesterol Homeostasis.Molecules (Basel, Switzerland) · 2020Review
- Review
- Alcohol Modulation of Amyloid Precursor Protein in Alzheimer's Disease.Journal of drug and alcohol research · 2020Article
- Altered Cytoskeletal Composition and Delayed Neurite Elongation in tauNeuroscience · 2019Article
- The Influence of Nicotinamide on Health and Disease in the Central Nervous System.International journal of tryptophan research : IJTR · 2018Review
- TauNeuroscience · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
A growing body of evidence suggests that beta-amyloid (Abeta), the main component of senile plaques, induces abnormal posttranslational processing of the microtubule-associated protein tau. We have recently described that, in addition to increasing tau phosphorylation, Abeta enhanced calpain activity leading to the generation of a toxic 17 kDa tau fragment in cultured hippocampal neurons. How aging, the greatest Alzheimer's disease (AD) risk factor, might regulate this proteolytic event remains unknown. In this study, we assessed the susceptibility of cultured hippocampal neurons to Abeta-dependent 17 kDa tau production at different developmental stages. Our results revealed that mature neurons were more susceptible to Abeta-induced calpain activation leading to the generation of this fragment than young neurons. In addition, the production of this fragment correlated with a decrease in cell viability in mature hippocampal neurons. Second, we determined whether membrane cholesterol, a suspect player in AD, might mediate these age-dependent differences in Abeta-induced calpain activation. Filipin staining and an Amplex Red cholesterol assay showed that mature neuron membrane cholesterol levels were significantly higher than those detected in young ones. Furthermore, decreasing membrane cholesterol in mature neurons reduced their susceptibility to Abeta-dependent calpain activation, 17 kDa tau production, and cell death, whereas increasing membrane cholesterol in young neurons enhanced these Abeta-mediated cellular processes. Finally, fura-2 calcium imaging indicated that membrane cholesterol alterations might change the vulnerability of cells to Abeta insult by altering calcium influx. Together these data suggested a potential role of cholesterol in linking aging to Abeta-induced tau proteolysis in the context of AD.
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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.