Abstract
Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD) progression and is associated with synaptic damage and neuronal death. Epidemiological and experimental studies indicate that hypercholesterolemia and hyperhomocysteinemia increase susceptibility to AD; however, the exact impact and mechanisms involved are largely unknown. Few studies have addressed the combined effects of the above compounds, which are considered to be risk factors for developing AD, on Aβ-induced neurotoxicity. The aim of the present work was to analyze the relationships between homocysteine (Hcy) and cholesterol and their role in Aβ toxicity in human neuroblastoma cells, as well as the mechanisms associated with this neurotoxicity. In addition to finding that Hcy is involved in cholesterol homeostasis in neurons, we demonstrate that the combined effect of cholesterol and Hcy in the presence of copper significantly increases the levels of reactive oxygen species and may render neurons more vulnerable to Aβ.
Keywords: Cu2+-amyloid-β complex, homocysteine toxicity, neuronal cholesterol accumulation, ROS production.
CNS & Neurological Disorders - Drug Targets
Title:Interplay Between Cholesterol and Homocysteine in the Exacerbation of Amyloid-β Toxicity in Human Neuroblastoma Cells
Volume: 12 Issue: 6
Author(s): Aydé Mendoza-Oliva, Patricia Ferrera and Clorinda Arias
Affiliation:
Keywords: Cu2+-amyloid-β complex, homocysteine toxicity, neuronal cholesterol accumulation, ROS production.
Abstract: Amyloid-β (Aβ) plays an important role in Alzheimer’s disease (AD) progression and is associated with synaptic damage and neuronal death. Epidemiological and experimental studies indicate that hypercholesterolemia and hyperhomocysteinemia increase susceptibility to AD; however, the exact impact and mechanisms involved are largely unknown. Few studies have addressed the combined effects of the above compounds, which are considered to be risk factors for developing AD, on Aβ-induced neurotoxicity. The aim of the present work was to analyze the relationships between homocysteine (Hcy) and cholesterol and their role in Aβ toxicity in human neuroblastoma cells, as well as the mechanisms associated with this neurotoxicity. In addition to finding that Hcy is involved in cholesterol homeostasis in neurons, we demonstrate that the combined effect of cholesterol and Hcy in the presence of copper significantly increases the levels of reactive oxygen species and may render neurons more vulnerable to Aβ.
Export Options
About this article
Cite this article as:
Mendoza-Oliva Aydé, Ferrera Patricia and Arias Clorinda, Interplay Between Cholesterol and Homocysteine in the Exacerbation of Amyloid-β Toxicity in Human Neuroblastoma Cells, CNS & Neurological Disorders - Drug Targets 2013; 12 (6) . https://dx.doi.org/10.2174/18715273113129990083
DOI https://dx.doi.org/10.2174/18715273113129990083 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Targeting Nitrosative Stress for Neurovascular Protection: New Implications in Brain Diseases
Current Drug Targets Agonist-Regulated Internalization and Desensitization of the Human Nociceptin Receptor Expressed in CHO Cells
Current Drug Targets Peripheral Neuropathy Induced by Paclitaxel: Recent Insights and Future Perspectives
Current Neuropharmacology Defective HIF Signaling Pathway and Brain Response to Hypoxia in Neurodegenerative Diseases: Not an “Iffy” Question!
Current Pharmaceutical Design Recent Insights on the Pro-Apoptotic Phenotype Elicited by Presenilin 2 and its Caspase and Presenilinase-Derived Fragments
Current Alzheimer Research Naphthoflavones as Antiproliferative Agents: Design, Synthesis and Biological Evaluation
Anti-Cancer Agents in Medicinal Chemistry Antitumor and Antiviral Activity of Pentacyclic Triterpenes
Mini-Reviews in Organic Chemistry Development of Prodrugs for Enzyme-Mediated, Tumor-Selective Therapy
Current Medicinal Chemistry - Anti-Cancer Agents Endocytosis, Intracellular Traffic and Fate of Cell Penetrating Peptide Based Conjugates and Nanoparticles
Current Pharmaceutical Design Repurposing of Anti-Diabetic Agents for the Treatment of Cognitive Impairment and Mood Disorders
Current Molecular Medicine Peptide-Drug Conjugate: A Novel Drug Design Approach
Current Medicinal Chemistry The Key Role of Membranes in Amyloid Formation from a Biophysical Perspective
Current Protein & Peptide Science A Role for Calcineurin in Alzheimers Disease
Current Neuropharmacology Novel Metals and Metal Complexes as Platforms for Cancer Therapy
Current Pharmaceutical Design Bone Morphogenetic Protein-Smad Pathway as Drug Targets for Osteoporosis and Cancer Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeting Glycosylation Aberrations to Improve the Efficiency of Cancer Phototherapy
Current Cancer Drug Targets Mitochondrial Permeability Transition as Target of Anticancer Drugs
Current Pharmaceutical Design Inhibition of Aurora A Kinase by Alisertib Induces Autophagy and Cell Cycle Arrest and Increases Chemosensitivity in Human Hepatocellular Carcinoma HepG2 Cells
Current Cancer Drug Targets Modulation of P2 Receptors on Pancreatic β-cells by Agonists and Antagonists: A Molecular Target for Type 2 Diabetes Treatment
Current Diabetes Reviews Thalidomide as an Antiangiogenic Drug in the Treatment of Multiple Myeloma
Letters in Drug Design & Discovery