Title : The effect of antioxidants on oxidative stress and amyloid-beta peptide plaques in CL2006 and CL4176 mutated C. elegans exhibiting alzheimer's disease symptoms through an analysis of effective increases in motility and mortality rates
Abstract:
Alzheimer's disease is characterized by the presence of beta-amyloid plaques in the brain. There is speculation in identifying potential therapeutic agents to mitigate their formation. Oxidative stress (OS)- the imbalance of reactive oxygen species and the body’s ability to detoxify itself and repair the damage caused by excess oxygen- is a potential contributor to the triggering of plaque and tangle formations as well as increased faster degeneration. The oxidative damage is shown to be in direct relation with A???? plaque collection and tau NFT deposition as well as decreased SOD levels needed to regulate them. To combat this, supplemental antioxidants introduced could lower plaque levels by increasing production of regulating enzymes. This study aimed to investigate the effects of N-acetylcysteine (NAC), beta-hydroxybutyrate (BHB), and Vitamin C on the preventability and reduction of the effects and presence of beta-amyloid plaque accumulation in C. elegans models (Cl2006 and CL4176). These C. elegans strains expressing human beta-amyloid were utilized to mimic key aspects of Alzheimer's pathology like decreased mobility and death rates, specifically due to the rol-1 mutation in CL2006 that causes curvatures and spasticity when plaque accumulation is present. The nematodes were treated with a 0.72M solution of N-Acetylcysteine, 0.69M solution of Ascorbic Acid, or a .94M solution of ????- Hydroxy ????- Methyl butyrate over the course of a 5-day period. Quantitative analysis was performed throughout experimentation using video analysis software which provided data to the impact of the treatments on C. elegans locomotion as well as death rates (_/100) per day. Preliminary results indicate that NAC, BHB, and Vitamin C exhibit varying degrees of efficacy in reducing beta-amyloid plaque burden in the Cl2006 and CL4176 models resulting in increased mobility, consistent direction and speed, even bending angles, less spastic movement, and centroid points that were all consistent with a control unmutated strain (N2). They also had significant effect on death rates resulting in an average of 4-5 less deaths from the start of the experimentation, pre supplemental addition. This investigation sheds light on the potential of NAC, BHB, and Vitamin C as therapeutic agents against beta-amyloid plaques, providing insights into their individual and synergistic effects in a C. elegans model with potential relation to human studies.
