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Cholesterol Potentiates β-Amyloid-Induced Toxicity in Human Neuroblastoma Cells: Involvement of Oxidative Stress

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Abstract

Alterations in brain cholesterol concentration and metabolism seem to be involved in Alzheimer’s disease (AD). In fact, several experimental studies have reported that modification of cholesterol content can influence the expression of the amyloid precursor protein (APP) and amyloid β peptide (Aβ) production. However, it remains to be determined if changes in neuronal cholesterol content may influence the toxicity of Aβ peptides and the mechanism involved. Aged mice, AD patients and neurons exposed to Aβ, show a significant increase in membrane-associated oxidative stress. Since Aβ is able to promote oxidative stress directly by catalytically producing H2O2 from cholesterol, the present work analyzed the effect of high cholesterol incorporated into human neuroblastoma cells in Aβ-mediated neurotoxicity and the role of reactive oxygen species (ROS) generation. Neuronal viability was studied also in the presence of 24S-hydroxycholesterol, the main cholesterol metabolite in brain, as well as the potential protective role of the lipophilic statin, lovastatin.

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Acknowledgments

The authors thank Karina Hernández-Ortega for assistance with microscopic analysis and Isabel Pérez-Montfort for correction of the English manuscript. This work was supported by CONACyT 48633 and PAPIIT IN217806 grants to C. Arias and PAPIIT IN202007 grant to M. Valverde.

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  1. Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70-228, 04510, Mexico, DF, Mexico

    Patricia Ferrera, Octavio Mercado-Gómez, Martín Silva-Aguilar, Mahara Valverde & Clorinda Arias

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  1. Patricia Ferrera
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  2. Octavio Mercado-Gómez
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  3. Martín Silva-Aguilar
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Correspondence to Clorinda Arias.

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Special issue article in honor of Dr. Ricardo Tapia.

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Ferrera, P., Mercado-Gómez, O., Silva-Aguilar, M. et al. Cholesterol Potentiates β-Amyloid-Induced Toxicity in Human Neuroblastoma Cells: Involvement of Oxidative Stress. Neurochem Res 33, 1509–1517 (2008). https://doi.org/10.1007/s11064-008-9623-y

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  • DOI: https://doi.org/10.1007/s11064-008-9623-y

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