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

Jianrong Wu,Nian Wu,Miaosen Wu,Hongtao Zhang,Xiaobei Zhan

doi:10.3390/ijms222212338

Jianrong Wu, Nian Wu + Show 3 more

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https://doi.org/10.3390/ijms222212338

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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.

Highlights

Alzheimer’s disease (AD) is a common progressive neurodegenerative disease that is clinically characterized by cognitive impairments
mannuronic acid-sialic acid conjugate (MOS-Sia) of different structures was synthesized according to Scheme 1
MOS-NH2 was reacted with Nacetylneuraminic acid directly through reductive amination, and the obtained conjugate was denoted as MOS-Sia1, with a conversion yield of 75.6% (±0.52)

Summary

Introduction

Alzheimer’s disease (AD) is a common progressive neurodegenerative disease that is clinically characterized by cognitive impairments. According to data released by the International Alzheimer’s Association, one patient with dementia occurs worldwide every 3.2 s [1]. Acetylocholinesterase inhibitors include Donepezil, Galantamine, and Rivastigmine. Another therapeutic agent approved for moderate to severe AD is the noncompetitive N-methyld-aspartate (NMDA) receptor antagonist Memantine [2]. The recent approval request to the FDA for the monoclonal antibody Aducanumab (Biogen) is controversial [4]. Following these controversies, the FDA did not grant full approval of the Aducanumab medication

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