Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo.

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Biosynthesis of a water solubility-enhanced succinyl glucoside derivative of luteolin and its neuroprotective effect.

The natural flavonoids luteolin and luteoloside have anti-bacterial, anti-inflammatory, anti-oxidant, anti-tumour, hypolipidemic, cholesterol lowering and neuroprotective effects, but their poor water solubility limits their application in industrial production and the pharmaceutical industry. In this study, luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside, a new compound that was prepared by succinyl glycosylation of luteolin by the organic solvent tolerant bacterium Bacillus amyloliquefaciens FJ18 in an 8.0% DMSO (v/v) system, was obtained and identified. Its greater water solubility (2293 times that of luteolin and 12 232 times that of luteoloside) provides the solution to the application problems of luteolin and luteoloside. The conversion rate of luteolin (1.0 g l-1 ) was almost 100% at 24 h, while the yield of luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside reached 76.2%. In experiments involving the oxygen glucose deprivation/reoxygenation injury model of mouse hippocampal neuron cells, the cell viability was significantly improved with luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside dosing, and the expressions of the anti-oxidant enzyme HO-1 in the nucleus increased, providing a neuroprotective effect for ischemic cerebral cells. The availability of biosynthetic luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside, which is expected to replace luteolin and luteoloside, would effectively expand the clinical application value of luteolin derivatives.

A Novel Formononetin Derivative Promotes Anti-ischemic Effects on Acute Ischemic Injury in Mice.

Natural flavonoids, formononetin and ononin, possess antioxidant, antibacterial, anti-inflammatory and neuroprotective effects. Many complications caused by SARS-CoV-2 make patients difficult to recover. Flavonoids, especially formononetin and ononin, have the potential to treat SARS-CoV-2 and improve myocardial injury. However, their poor water solubility, poor oral absorption, high toxicity, and high-cost purification limit industrial practical application. Succinylation modification provides a solution for the above problems. Formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside (FMP), a new compound, was succinyl glycosylated from formononetin by the organic solvent tolerant bacteria Bacillus amyloliquefaciens FJ18 in a 10.0% DMSO (v/v) system. The water solubility of the new compound was improved by over 106 times compared with formononetin, which perfectly promoted the application of formononetin and ononin. The conversion rate of formononetin (0.5 g/L) was almost 94.2% at 24 h, while the yield of formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside could achieve 97.2%. In the isoproterenol (ISO)-induced acute ischemia mice model, the myocardial injury was significantly improved with a high dose (40 mg/kg) of formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside. The lactate dehydrogenase level was decreased, and the catalase and superoxide dismutase levels were increased after formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside treatment. Thus, formononetin-7-O-ß-(6″-O-succinyl)-D-glucoside has high water solubility, low toxicity, and shows significant antimyocardial ischemia effects.