Bahn G, Park JS, Yun UJ, Lee YJ, Choi Y, Park JS, Baek SH, Choi BY, Cho YS, Kim HK, Han J, Sul JH, Baik SH, Lim J, Wakabayashi N, Bae SH, Han JW, Arumugam TV, Mattson MP, Jo DG. 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.

    View all comments by Stefan Lichtenthaler

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