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
-
Focal Adhesion Kinase as a Therapeutic Target of Bortezomib
Anti-Cancer Agents in Medicinal Chemistry Lactate Transporters and pH Regulation: Potential Therapeutic Targets in Glioblastomas
Current Cancer Drug Targets Recent Advances in the Discovery of GSK-3 Inhibitors from Synthetic Origin in the Treatment of Neurological Disorders
Current Drug Targets Plausible Improvements for Selective Targeting of Dopamine Receptors in Therapy of Parkinson’s Disease
Mini-Reviews in Medicinal Chemistry Effects of LPA and S1P on the Nervous System and Implications for Their Involvement in Disease
Current Drug Targets Na<sup>+</sup>/K<sup>+</sup> ATPase Inhibitors in Cancer
Current Drug Targets Pathophysiology of Blood-Spinal Cord Barrier in Traumatic Injury and Repair
Current Pharmaceutical Design Apoptosis Induction by Erucylphosphohomocholine via the 18 kDa Mitochondrial Translocator Protein: Implications for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry β-Galactosylated Alkyl-oligoamine Derivatives of Polyethylenimine Enhanced pDNA Delivery into Hepatic Cells with Reduced Toxicity
Current Nanoscience Pluripotent Stem Cell-Derived Somatic Stem Cells as Tool to Study the Role of MicroRNAs in Early Human Neural Development
Current Molecular Medicine Expression, Distribution and Regulation of Phosphodiesterase 5
Current Pharmaceutical Design Apoptosis-Inducing Activity of the S100A8/A9 Heterodimer
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Reactive Oxygen Species, Redox Signaling and Neuroinflammation in Alzheimer's Disease: The NF-κB Connection
Current Topics in Medicinal Chemistry The ARRONAX Project
Current Radiopharmaceuticals Altered Glutamate Neurotransmission and Behaviour in Dementia: Evidence from Studies of Memantine
Current Molecular Pharmacology Status of Flavonols as P-Glycoprotein Inhibitors in Cancer Chemotherapy
Current Cancer Therapy Reviews The Influence of Cox-2 and Bioactive Lipids on Hematological Cancers
Current Angiogenesis (Discontinued) Targeting Glycosylation Aberrations to Improve the Efficiency of Cancer Phototherapy
Current Cancer Drug Targets Good, Bad, Mobile Elements: Genome’s Most Successful “Parasites” as Emerging Players in Cell and Organismal Aging
Current Pharmaceutical Design Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?
Current Drug Targets