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. 2021 Nov 15;22(22):12338.
doi: 10.3390/ijms222212338.

An Oligomannuronic Acid-Sialic Acid Conjugate Capable of Inhibiting Aβ42 Aggregation and Alleviating the Inflammatory Response of BV-2 Microglia

Jianrong Wu  1 , Miaosen Wu  1 , Hongtao Zhang  1 , Xiaobei Zhan  1 , Nian Wu  2
Affiliations

An Oligomannuronic Acid-Sialic Acid Conjugate Capable of Inhibiting Aβ42 Aggregation and Alleviating the Inflammatory Response of BV-2 Microglia

Jianrong Wu et al. Int J Mol Sci. .

Abstract

Oligomannuronic acid (MOS) from seaweed has antioxidant and anti-inflammatory activities. In this study, MOS was activated at the terminal to obtain three different graft complexes modified with sialic acid moiety (MOS-Sia). The results show that MOS-Sia addition can reduce the β-structure formation of Aβ42, and the binding effect of MOS-Sia3 is more obvious. MOS-Sia conjugates also have a better complexing effect with Ca2+ while reducing the formation of Aβ42 oligomers in solutions. MOS-Sia3 (25-50 μg/mL) can effectively inhibit the activation state of BV-2 cells stimulated by Aβ42, whereas a higher dose of MOS-Sia3 (>50 μg/mL) can inhibit the proliferation of BV-2 cells to a certain extent. A lower dose of MOS-Sia3 can also inhibit the expression of IL-1β, IL-6, TNF-α, and other proinflammatory factors in BV-2 cells induced by Aβ42 activation. In the future, the MOS-Sia3 conjugate can be used to treat Alzheimer's disease.

Keywords: Alzheimer’s disease; microglia; oligomannuronic acid; sialic acid; β-amyloid.

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Conflict of interest statement

There are no conflict to declare.

Figures

Figure 1
Figure 1
MS spectra of MOS-Sia. (a) MOS-Sia1, (b) MOS-Sia2, and (c) MOS-Sia3.
Figure 1
Figure 1
MS spectra of MOS-Sia. (a) MOS-Sia1, (b) MOS-Sia2, and (c) MOS-Sia3.
Figure 2
Figure 2
Residual soluble Aβ in supernatant after interaction with MOS-Sia, metal ion, and Aβ42. Note: Molar ratio of Aβ42 to metal ion was set as 1:1, with incubation for 24 h. Data are shown as the mean ± SD of triplicates.
Figure 3
Figure 3
Fluorescence detection of the effect of MOS-Sia on Aβ42 aggregation by ThT staining. Data are shown as the mean ± SD of triplicates.
Figure 4
Figure 4
CD analysis of the interaction between MOS-Sia and Aβ42.
Figure 5
Figure 5
Effect of MOS-Sia3 on the cell growth of BV-2. Data are shown as the mean ± SD of triplicates.
Figure 6
Figure 6
Morphological observation of BV-2 cells after administration with MOS-Sia3 and Aβ42.
Figure 7
Figure 7
Effects of MOS-Sia3 on cytokine secretion in BV-2 cells induced by Aβ42. Captions: Black bar, 24 h of culture; gray bar: 48 h of culture. Data are shown as the mean ± SD of triplicates with good reproducibility. SD is represented as error bars. Statistically significant differences are indicated: ** for p ≤ 0.01, and *** for p ≤ 0.001.
Figure 7
Figure 7
Effects of MOS-Sia3 on cytokine secretion in BV-2 cells induced by Aβ42. Captions: Black bar, 24 h of culture; gray bar: 48 h of culture. Data are shown as the mean ± SD of triplicates with good reproducibility. SD is represented as error bars. Statistically significant differences are indicated: ** for p ≤ 0.01, and *** for p ≤ 0.001.
Scheme 1
Scheme 1
Preparation of MOS-Sia by reductive amination, amidation, and thiol condensation.
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