Researchers identify KEAP1 as AD target

In a manuscript published in PLoS Genetics, U.K. researchers identified Kelch-like ECH associated protein 1 (KEAP1) as a potential target to treat Alzheimer's disease. In a fly model, the scientists found that inhibition of KEAP1 activity prevented neuronal toxicity caused by beta amyloid, through its stimulation of nuclear factor (erythroid-derived 2)-like 2 (NFE2L2; NRF2) activity.

NRF2 is an established target in neurology, but activation of the pathway is associated with toxicity. According to BioCentury's BCIQ database, at least two NRF2-targeting compounds are in development for neurological indications. Omaveloxolone (oral RTA 408) from Reata Pharmaceuticals Inc. (NASDAQ:RETA) is in Phase II testing to treat Friedreich's ataxia, while CAT-4001 from Catabasis Pharmaceuticals Inc. (NASDAQ:CATB) is in preclinical development to treat Friedreich's ataxia and amyotrophic lateral sclerosis...