How Nicotinamide Riboside affects rate of paralysis in c. elegans

• Karen Melo-Rubio, Biological Sciences, University of Delaware

• Jessica Tanis, Biological Sciences, University of Delaware

Alzheimer’s Disease is a neurodegenerative disease that affects millions of individuals and has no effective treatment thus far. Multiple factors contribute to disease pathogenesis, including toxic amyloid-beta (Aβ) peptide deposition, energy crisis, and oxidative stress. AD is characterized by synapse and neuron loss in the brain and accompanied by the buildup of protein-containing deposits and neurofibrillary tangles. Recent studies also suggest that Aβ oligomers induce AD-related synaptic dysfunction and that managing toxic Aβ oligomers might offer a viable strategy for controlling Aβ-associated toxicity.  Nicotinamide adenine dinucleotide (NAD+) is a coenzyme and electron acceptor that functions in several hundred human enzymatic reactions and energy synthesis. Decreased levels of NAD+ are common in aging humans, mice, and C. elegans, and is a symptom of AD. Consequently, this hinders cellular respiration, resulting in decreased adenosine triphosphate (ATP) levels and neuronal death. NAD+ precursors such as NR (nicotinamide riboside) have been shown in past studies to be an effective and efficient way to increase NAD+ levels. The extensively researched nematode worm C. elegans can be genetically modified to express human Aβ through transgenic engineering. The model we are using utilizes a temperature-sensitive mutation in the mRNA surveillance system, enabling the controlled muscle expression of an Aβ transgene when the temperature is increased. This engineered condition leads to a consistent paralysis phenotype as a result of a temperature upshift. The advantages of C. elegans for studying aging, coupled with its extensive range of applicable genetic and molecular tools, have established this organism as a favored model for investigating proteotoxicity. My experiments utilized C. elegans expressing Aβ 1-42 oligomers in their body wall muscles to see the effects of NR on the rate of paralysis. I used the strain GMC101, GMC101 on 1mM NR, and .5 mM NR. My data suggests that feeding the diet of E. coli alongside .5 mM of NR slows down the rate of paralysis in C. elegans. However, feeding it 1mM NR seemingly accelerated the rate of paralysis. By hour 6, all of the worms were paralyzed. In the future, I will run more paralysis assays to obtain more accurate results and have a tighter regulation.