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KCI등재 학술저널

Inhibition of &#1346;-amyloid<SUB>1-40</SUB> Peptide Aggregation and Neurotoxicity by Citrate

Inhibition of &#1346;-amyloid<SUB>1-40</SUB> Peptide Aggregation and Neurotoxicity by Citrate

The accumulation of &#1346;-amyloid (A&#1346;) aggregates is a characteristic of Alzheimer s disease (AD). Furthermore, these aggregates have neurotoxic effects on cells, and thus, molecules that inhibit A&#1346; aggregate formation could be valuable therapeutics for AD. It is well known that aggregation of A&#1346; depends on its hydrophobicity, and thus, in order to increase the hydrophilicity of A&#1346;, we considered using citrate, an anionic surfactant with three carboxylic acid groups. We hypothesized that citrate could reduce hydrophobicity and increase hydrophilicity of A&#1346;<sub>1-40</sub> molecules via hydrophilic/electrostatic interactions. We found that citrate significantly inhibited A&#1346;<sub>1-40</sub> aggregation and significantly protected SH-SY5Y cell line against A&#1346;<sub>1-40</sub> aggregates-induced neurotoxicity. In details, we examined the effects of citrate on A&#1346;<sub>1-40</sub> aggregation and on A&#1346;<sub>1-40</sub> aggregates-induced cytotoxicity, cell viability, and apoptosis. Th-T assays showed that citrate significantly inhibited A&#1346;<sub>1-40</sub> aggregation in a concentration- dependent manner (Th-T intensity: from 91.3% in 0.01 mM citrate to 82.1% in 1.0 mM citrate vs. 100.0% in A&#1346;<sub>1-40</sub> alone). In cytotoxicity and viability assays, citrate reduced the toxicity of A&#1346;<sub>1-40</sub> in a concentration-dependent manner, in which the cytotoxicity decreased from 107.5 to 102.3% as compared with A&#1346;<sub>1-40</sub> aggregates alone treated cells (127.3%) and the cell viability increased from 84.6 to 93.8% as compared with the A&#1346;<sub>1-40</sub> aggregates alone treated cells (65.3%). Furthermore, Hoechst 33342 staining showed that citrate (1.0 mM) suppressed A&#1346;<sub>1-40</sub> aggregates-induced apoptosis in the cells. This study suggests that citrate can inhibit A&#1346;<sub>1-40</sub> aggregation and protect neurons from the apoptotic effects of A&#1346;<sub>1-40</sub> aggregates. Accordingly, our findings suggest that citrate administration should be viewed as a novel neuroprotective strategy for AD.

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