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.
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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 |
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