Ferrera Patricia, Mercado-Gómez Octavio, Silva-Aguilar Martín, Valverde Mahara, Arias Clorinda
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70-228, 04510, Mexico, DF, Mexico.
Neurochem Res. 2008 Aug;33(8):1509-17. doi: 10.1007/s11064-008-9623-y. Epub 2008 Feb 21.
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 beta peptide (Abeta) production. However, it remains to be determined if changes in neuronal cholesterol content may influence the toxicity of Abeta peptides and the mechanism involved. Aged mice, AD patients and neurons exposed to Abeta, show a significant increase in membrane-associated oxidative stress. Since Abeta is able to promote oxidative stress directly by catalytically producing H(2)O(2) from cholesterol, the present work analyzed the effect of high cholesterol incorporated into human neuroblastoma cells in Abeta-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.
大脑胆固醇浓度和代谢的改变似乎与阿尔茨海默病（AD）有关。事实上，多项实验研究报告称，胆固醇含量的改变会影响淀粉样前体蛋白（APP）的表达和淀粉样β肽（Aβ）的产生。然而，神经元胆固醇含量的变化是否会影响Aβ肽的毒性及其相关机制仍有待确定。老年小鼠、AD患者以及暴露于Aβ的神经元，均显示出膜相关氧化应激的显著增加。由于Aβ能够通过催化胆固醇产生H(2)O(2)直接促进氧化应激，因此本研究分析了高胆固醇掺入人神经母细胞瘤细胞对Aβ介导的神经毒性的影响以及活性氧（ROS）生成的作用。同时也研究了在存在大脑中主要的胆固醇代谢产物24S-羟基胆固醇的情况下神经元的活力，以及亲脂性他汀类药物洛伐他汀的潜在保护作用。
