Abstract: Polysaccharides are macromolecular complexes that have various biological activities. In vivo and in vitro studies have shown that polysaccharides play neuroprotective roles through multiple mechanisms; consequently, they have potential in the prevention and treatment of neurodegenerative diseases. This paper summarizes related research published during 2015–2020 and reviews advances in the understanding of the neuroprotective effects of bioactive polysaccharides. This review focuses on 15 bioactive polysaccharides from plants and fungi that have neuroprotective properties against oxidative stress, apoptosis, neuroinflammation, and excitatory amino acid toxicity mainly through the regulation of nuclear factor kappa-B, phosphatidylinositol-3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor-E2-related factor 2/ hemeoxygenase-1, c-jun N-terminal kinase, protein kinase B-mammalian target of rapamycin, and reactive oxygen species-nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 signaling pathways. Natural bioactive polysaccharides have potential in the prevention and treatment of neurodegenerative diseases because of their advantageous characteristics, including multi-targeting, low toxicity, and synergistic effects. However, most of the recent related research has focused on cell and animal models. Future randomized clinical trials involving large sample sizes are needed to validate the therapeutic benefits of these neuroprotective polysaccharides in patients having neurodegenerative diseases.

Key words: Alzheimer’s disease, apoptosis, experimental research, neurodegeneration, neuroinflammation, neuroprotective, oxidative stress, Parkinson’s disease, polysaccharides, protective mechanisms