Transgenic Caenorhabditis elegans Models of Learning and Memory Dysfunction in MitoNEET-/- and Alzheimer’s Disease

Sofhia Elad*, Jacob Boos, Hanna Jandrain*, Sarah Faber*, and Werner Geldenhuys

Department of Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26506

Presentation Category: Biological & Biochemical Sciences (Poster Presentation #96)

Student’s Major: Chemistry

Alzheimer’s Disease (AD) is a progressive, neurodegenerative disease characterized by the presence of extracellular amyloid plaques composed of the amyloid-β42(Aβ42) protein and neurofibrillary tangles composed of the aggregated hyperphosphorylated tau microtubule protein. Both pathologies contribute to reactive oxygen species (ROS) production leading to oxidative stress, mitochondrial dysfunction, and ultimately neuronal death. MitoNEET (CISD1) is an iron-sulfur [Fe-S] cluster containing protein located on the outer mitochondrial membrane. These clusters, having been involved with redox reactions, neutralize ROS and mediates mitochondrial function. The role of mitoNEET on oxidative stress and mitochondrial function has previously been modeled in diseases including diabetes and cancer; however, the role of mitoNEET in AD has yet to be widely studied in the field. With the relationship between mitoNEET and AD not yet evaluated, we aim to investigate the loss of mitoNEET contributes to mitochondrial dysfunction compared to those observed in AD using transgenic Caenorhabditis elegans models. We hypothesized that mitoNEET knockout models will present behavioral and physiological deficits similar to those observed in AD. To understand the relationship of our hypothesis, we use transgenic C. elegans strains, expressing 1) a global mitoNEET knockout, 2) transgenic AD strain expressing the Aβ42 pathology, and 3) their wild-type controls, assessing learning and memory behaviors, oxidative stress resistance, and mitochondrial functions. Collectively, the data from this study will help progress the field of AD and aging research and provide insights on the mechanisms that mitoNEET declination may contribute to the progression of AD.

Funding: National Institutes of Health

Program/mechanism supporting research/creative efforts: Other, WVU INBRE