κ-Carrageenan Oligosaccharides Protect Nerves by Regulating Microglial Autophagy in Alzheimer's Disease

ACS Chem Neurosci. 2023 Sep 20;14(18):3540-3550. doi: 10.1021/acschemneuro.3c00460. Epub 2023 Aug 31.

Abstract

κ-Carrageenan is a linear sulfated polysaccharide extracted from the cell wall of marine red algae, and its enzymatically digested oligosaccharides (KOS) can inhibit microglial hyperactivation. Alzheimer's disease (AD) is a common chronic neurodegenerative disease, characterized by cognitive and memory impairment accompanied by nerve cell damage. Microglia activation causing enhancement of proinflammatory effects and neurotoxicity is one of the early events in AD disease. In this study, whether KOS have therapeutic or preventive effects in the AD model prepared from APP/PS1 transgenic mice was determined. Learning and memory of AD mice were detected by water maze experiments, and microglial activation-related protein expression and deposition of APP and Aβ1-42 in the brain were examined. The effects of KOS on expressed inflammatory factors and inflammation-related proteins by microglia were tested by cell experiments. Transwell coculture was used to investigate the effect of microglia on neural cell activity after KOS treatment. The results showed that KOS could relieve the clinical symptoms in AD mice, and a decrease in the expression of inflammatory factors and inflammation-related proteins in brain tissue was detected. KOS alleviated nerve cell apoptosis by inhibiting the overactivation of microglia, thus exhibiting neuroprotective effects. Exploring the protective effect of KOS inhibition of microglia inflammation is expected to provide a theoretical basis for KOS as a therapeutic drug for neurodegenerative diseases.

Keywords: APP/PS1; Alzheimer’s disease; inflammation; microglia; oligosaccharides; κ-carrageenan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Animals
  • Autophagy
  • Carrageenan
  • Inflammation / drug therapy
  • Mice
  • Mice, Transgenic
  • Microglia
  • Neurodegenerative Diseases*
  • Oligosaccharides / pharmacology

Substances

  • Carrageenan
  • Oligosaccharides