Examining NRF2 expression as a potential therapy for Alzheimer’s disease using an in vitro cell model

Alzheimer’s disease (AD) is a neurodegenerative condition that contributes to the majority of dementia cases worldwide. The exact cause of AD remains elusive, and the study of its disease biology is hampered by the lack of in vitro and in vivo models that are representative of the condition, and the absence of disease-modifying treatments. In this project, we attempted to use the most accurate cellular model of AD currently available to test whether an intervention that reduces oxidative stress, a common pathological feature of AD, can provide therapeutic benefits. The cellular model we used is a 3-dimensional cell matrix formed by differentiated immortalized human neural-progenitors which was previously shown to generate many key feature of AD pathobiology, such as phosphorylated Tau and A aggregates. Our therapeutic intervention was the overexpression of Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that counters oxidative stress in normal cells and was found to ameliorate the symptoms of AD in mice. This project first made an attempt to reproduce the 3-dimensional AD cell culture model, and then test the effectiveness of NRF2 overexpression as a treatment option