To study the role of oxidative stress on Alzheimer’s Disease and neurodegeneration using redox sensitive proteins

Abstract

Oxidative stress plays an important role in the neuropathology of many progressive neurodegenerative disorders such as Alzheimer’s Disease and Parkinson’s Disease. An excess of aggregated beta amyloid is one of the major markers of Alzheimer’s Disease, and this causes an increase in the oxidative stress. Moreover, in a positive feedback loop, oxidative stress seems to increase the production of beta amyloid as well. Thus, it would be very interesting to be able to study the real-time changes in the redox state of the cell in response to oxidative stress, first in cell lines, and eventually in primary neurons to get a better understanding of the disease. To this end, we performed live-cell imaging experiments on human embryonic kidney cells, and observed an interesting phenomenon upon addition of an external oxidativestress causing agent (tert-Butyl Hydroperoxide), wherein the oxidative state of the cell seems to come back to normal after an hour or two. This is potentially due to some antioxidant mechanisms present in the cells. This rebound phenomenon was however not observed in Neuroblastoma cells. It remains to be seen how primary neurons will react to oxidative stress, and whether wild type neurons will show a different oxidative state as compared to neurons transgenic for Alzheimer’s mutations which might have an intrinsically higher level of oxidative stress due to the presence of excess beta amyloid.