Topic: NFE2L2

Metal exposure is an intriguing potential culprit in the cause of sporadic amyotrophic lateral sclerosis (ALS). Lead (Pb), mercury (Hg), cadmium (Cd) and arsenic (As) are singled out among the ten chemicals of major public health concern by the World Health Organisation. There are numerous case reports and case-control studies linking those metals to an ALS phenotype. Additionally, some studies have demonstrated higher levels of these metals in the blood, cerebrospinal fluid, urine, or spinal cords of patients with ALS compared to controls. Recently, it has been proposed that the interaction b

The transcription factor Nrf2 (encoded by the Nfe2l2 gene) is a widely-expressed stress-responsive master regulator of several aspects of homeostatic physiology. Nrf2 plays a key role in preventing oxidative stress and inflammation. In the brain, Nrf2 is highly expressed by endothelial cells. Brain endothelial cells (BECs) are the key component of the blood brain barrier (BBB), which controls brain homeostasis. The role of BEC Nrf2 expression in maintaining homeostasis is not fully understood. In this project, through gain- and loss function experiments, we have found that Nrf2 activity in BEC