Examining the levels of ganglioside and cholesterol in cell membrane on attenuation the cytotoxicity of beta-amyloid peptide

Ming Shen Lin, Liang Yu Chen, Steven S.S. Wang, Yung Chang, Wen Yih Chen

研究成果: 雜誌貢獻期刊論文同行評審

31 引文 斯高帕斯(Scopus)

摘要

The deposition of β-amyloid (Aβ) on cell membranes is considered as one of the primary factors in having Alzheimer's disease (AD). Recent studies have suggested that certain components of plasma membrane, ganglioside and cholesterol could accelerate the accumulation of Aβ on the plasma membranes. However, the effect of cholesterol and ganglioside (GM1) on Aβ cytotoxicity is still a controversial issue. The aim of this study is to understand the roles of GM1 and cholesterol in AD by using PC12, a neuron-like cell. The effects of the sequence, conformation, and concentration of Aβ on cytotoxicity were also investigated. Monomeric Aβ could attack the plasma membrane resulting in cytotoxicity, however, fibrillar Aβ was found to be less toxic. Our results showed that Aβ (1-40) was more toxic than Aβ (25-35) and the cytotoxicity of Aβ was proportional to its concentration. Besides, the depletion of GM1 from plasma membrane, it would block the Aβ-induced cytotoxicity. Decreasing the cholesterol level by around 30% could attenuate the cytotoxicity of Aβ. These findings validate our idea that the cholesterol could stabilize the lateral pressure derived from the formation of GM1-Aβ complex on the membrane surface. Furthermore, both GM1 and cholesterol are essential in mechanism of Aβ accumulation and could modulate the cytotoxicity of monomeric Aβ.

原文???core.languages.en_GB???
頁(從 - 到)172-177
頁數6
期刊Colloids and Surfaces B: Biointerfaces
65
發行號2
DOIs
出版狀態已出版 - 1 9月 2008

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