Modeling Alzheimer’s Disease in Caenorhabditis elegans

Abstract

Alzheimer’s disease (AD) is the most frequent cause of dementia. After decades of research, we know the importance of the accumulation of protein aggregates such as β-amyloid peptide and phosphorylated tau. We also know that mutations in certain proteins generate early-onset Alzheimer’s disease (EOAD), and many other genes modulate the disease in its sporadic form. However, the precise molecular mechanisms underlying AD pathology are still unclear. Because of ethical limitations, we need to use animal models to investigate these processes. The nematode Caenorhabditis elegans has received considerable attention in the last 25 years, since the first AD models overexpressing Aβ peptide were described. We review here the main results obtained using this model to study AD. We include works studying the basic molecular mechanisms of the disease, as well as those searching for new therapeutic targets. Although this model also has important limitations, the ability of this nematode to generate knock-out or overexpression models of any gene, single or combined, and to carry out toxicity, recovery or survival studies in short timeframes with many individuals and at low cost is difficult to overcome. We can predict that its use as a model for various diseases will certainly continue to increase.

Holothuria scabra extracts confer neuroprotective effect in C. elegans model of Alzheimer's disease by attenuating amyloid-β aggregation and toxicity

“… 6 C. elegan s is a small, free-living nematode that has many biological advantages, such as short and reproducible lifespan and life cycle, ease of maintenance, tractable genetic manipulation, and significant conservation of genes with human; thus, it is widely accepted as a suitable animal model for studying aging and neurodegenerative diseases. 21 , 22 , 23 Particularly, in case of AD multiple transgenic strains have been generated to express amyloid-β aggregation and utilized as an in vivo AD model for testing the efficacy of extracts/compounds, as well as their potential mechanism against Aβ-induced neurotoxicity. 6 , 24 , 25 …”

Fluorescein-appended calixarene-functionalized supramolecular AIE-active liquid crystalline materials for self-assembly and bio-imaging applications

“…They are a classical animal model with a short lifespan, and simple anatomy and are easy to handle. 52–54 Published reports clearly indicate that nematodes are harmonious candidates for toxicological assessment for metal, metal oxide, and carbon-based nanoparticles. 55 In the present study, we selected dodecyloxy chain substituted fluorescent material ( 4d ) for imaging study due to its highly fluorescent nature and AIE properties.…”

Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease

“…Although C. elegans cannot generate endogenous Aβ because of the absence of β-secretase, exogenous expression methods have remedied this limitation by producing human β-amyloid peptides in muscle cells and pan neurons (Griffin et al, 2017). In recent years, researchers have used C. elegans to study the function of APP and presenilins and the function and mechanism of toxicity of Aβ and Tau (Alvarez et al, 2022). As of now, there is a good deal of toxicity models expressing normal or mutated Aβ in C. elegans.…”