While the mechanistic link between Nrf2 and TJs expression is unclear and will need to be studied further, these data, along with previously published work by us and others, strongly suggest that metformin could be a viable therapeutic option to offset some of the harmful effects associated with chronic smoking/vaping that can negatively impact the integrity of the BBB and the cerebrovascular system, thus promoting the onset and progression of many neurological disorders [24, 30, 44, 45, 74–76]. The gene discussed is NFE2L2; the disease is nervous system disorder.