450409 Modulation Effect of Acidulated Human Serum Albumin on Cu2+-Mediated Amyloid β-Protein Aggregation and Cytotoxicity

Monday, November 14, 2016
Grand Ballroom B (Hilton San Francisco Union Square)
Baolong Xie, Xiaoyan Dong2 and Yan Sun2, (1)Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China

Alzheimer’s disease (AD), a prevalent neurodegenerative disease, is characterized by dysfunction of memory. The main histofpathological hallmark of AD is senile plaques formed by amyloid β-proteins (Aβ) in the hippocampus and cortex. In addition, elevated levels of metal ions in plaques, mainly Cu2+ and Zn2+, indicate that they play a crucial role in Aβ aggregation in vivo. It has been proven that metal ions not only induce the generation of off-pathway Aβ aggregates but also lead to the formation of reactive oxygen species (ROS), which are harmful for nerve cells. Cerebral acidosis is another common complication of AD. Under mildly acidic conditions, Cu2+-Aβ species have a higher tendency to generate neurotoxic aggregates. In this work, we fabricated acidulated human serum albumin (A-HSA) to mitigate Cu2+-mediated Aβ42 aggregation and cytotoxicity at pH 6.6. Extensive experiments showed that A-HSA could alter the pathway of Cu2+-mediated Aβ42 aggregation and protect SH-SY5Y cells from cytotoxicity and oxidative damage induced by Cu2+-Aβ42 species. Noticeably, stopped-flow fluorescence analysis revealed that A-HSA changed the Cu2+-Aβ42 coordination mode from complex I to complex II on the millisecond timescale, which avoided the formation of aggregation-prone Cu2+-Aβ42 aggregates. Based on the findings, we proposed a mechanism of the modulation effect of A-HSA on inhibiting Cu2+-mediated Aβ42 aggregation and cytotoxicity under the mildly acidic condition.

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