Natural Bioactive Products and Alzheimer’s Disease Pathology: Lessons from Caenorhabditis elegans Transgenic Models

Abstract

Alzheimer’s disease (AD) is an age-dependent, progressive disorder affecting millions of people. Currently, the therapeutics for AD only treat the symptoms. Although they have been used to discover new products of interest for this disease, mammalian models used to investigate the molecular determinants of this disease are often prohibitively expensive, time-consuming and very complex. On the other hand, cell cultures lack the organism complexity involved in AD. Given the highly conserved neurological pathways between mammals and invertebrates, Caenorhabditis elegans has emerged as a powerful tool for the investigation of the pathophysiology of human AD. Numerous models of both Tau- and Aβ-induced toxicity, the two prime components observed to correlate with AD pathology and the ease of performing RNA interference for any gene in the C. elegans genome, allow for the identification of multiple therapeutic targets. The effects of many natural products in main AD hallmarks using these models suggest promising health-promoting effects. However, the way in which they exert such effects is not entirely clear. One of the reasons is that various possible therapeutic targets have not been evaluated in many studies. The present review aims to explore shared therapeutical targets and the potential of each of them for AD treatment or prevention.

Novel Flavonol Alkaloids in Green Tea: Synthesis, Detection, and Anti-Alzheimer’s Disease Effect in a Transgenic Caenorhabditis elegans CL4176 Model

“…elegans among different assays, suggesting that they might be promising anti-AD agents. Mechanistically, besides having strong antioxidant potency, quercetin can promote Aβ 1–42 protein degradation and macroautophagy, thus alleviating Aβ 1–42 aggregation and paralysis in the nematodes. , Flavonol alkaloids might also target protein degradation and macroautophagy but with enhanced anti-AD activities induced by extra N -ethyl-2-pyrrolidinone substitution, since they have an N -containing heterocycle enhancing presumably their polarity, solubility, availability and decreasing their toxicity (Table S14). At the same time, they all have a relatively smaller molecular weight, which is helpful for them to be developed as related drugs.…”

The role of Caenorhabditis elegans in the discovery of natural products for healthy aging

“…Several reviews on the longevity promoting effect of natural compounds were also published. 67,68 NPs active against transgenic C. elegans models of Alzheimer's disease were surveyed by Navarro-Hortal et al 69 Shen and coworkers 70,71 reviewed the use of C. elegans as a model for researching bioactive compounds in food against aging, obesity and Alzheimer's disease. A review on the oxidative and antioxidative potential of NP in C. elegans was also published recently.…”