Alginate is a linear block compound formed by β- Mannuronic oligosaccharides and α- Guluronate Oligoscharcharide linked by 1 à 4 glycoside bond. There are three kinds of structural fragments, namely PM fragment, PG fragment and PMG fragment. Among them, a series of mannuronic oligosaccharides can be prepared by degradation of polymannose uronic acid (PM).
Alzheimer's disease (AD), also known as senile dementia, is mainly manifested in the decline of cognitive and memory function, accompanied by a variety of behavioral disorders, daily life is basically unable to take care of itself. Soluble β-amyloidin (Aβ) aggregates to form insoluble fibers outside nerve cells, and finally precipitates to form aged plaques. Moreover, Aβfibers, whether oligomers or fibers, cause damage to neurons. Therefore, Aβ is one of the important pathological causes of AD. In addition, the hyperphosphorylation of Tau protein makes it dissociate from microtubule and loses its regulation on microtubule, which makes the normal assembly of microtubule impossible. Moreover, the hyperphosphorylation of Tau protein dissociated from microtubule results in the formation of phf-tau, and the formation of nerve fiber tangle (NFT), which results in the loss of basic morphology of neurons, and the neurotoxicity of Tau protein also occurs in the process of self-aggregation. This is also an important reason for the formation of AD. In addition, ad is also associated with many factors, such as aging, oxidative stress, glial inflammation, autophagy, mitochondrial disorder and so on.
The mannuronic oligosaccharide can not only inhibit Aβ aggregation in vitro, but also eliminate overexpression of Aβ, starch like precursor protein (APP) and β secretase (BACE1) in N2a-sw-APP695 cells by autophagy, and maintain cell homeostasis. In addition, manuronic oligosaccharide can effectively inhibit the aggregation of tau protein induced by heparin in vitro. Inhibiting the aggregation of tau protein can not only reduce the toxicity of tau protein aggregation into polymer structure, but also increase the content of tau protein monomer and promote the stability of microtubule. Mannuronic oligosaccharide can decrease the phosphorylation level of tau protein at position 202、262、396、404 of serine, which indicates that mannuronic oligosaccharide plays an active role in stabilizing microtubule and inhibiting tau protein aggregation. And the mannuronic oligosaccharide can also effectively reduce the phosphorylation level of the tau protein in the primary neuron of the hek293/ tau cell and the 3-tg mouse, and simultaneously improve the autophagy level of the primary neuron of the 3-to-tg mouse. The mannuronic oligosaccharide thus has the potential to antagonize the neurodegeneration, especially AD.