. NRF2/ARE pathway negatively regulates BACE1 expression and ameliorates cognitive deficits in mouse Alzheimer's models. Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12516-12523. Epub 2019 Jun 4 PubMed.


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  1. This is a compelling story with in vitro and in vivo experiments describing a new cellular pathway controlling BACE1 expression, activity, and amyloid pathology. Excitingly, they even found that a pharmacological activation of this pathway may be exploited to improve amyloid pathology and cognitive deficits in AD mice, suggesting a translational potential for the human disease. With the known strengths and weaknesses of small molecule BACE1 inhibitors in mind, a potential activation of the NRF2 pathway in humans may, thus, be most beneficial for primary or secondary prevention of AD.

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