Alzheimer’s disease (AD) is the most common type of dementia and is characterized by the accumulation of plaque deposits of the amyloid-β peptide in the brain. Levels of the enzyme BACE1, which produces amyloid-β plaques, are elevated in the brains of patients with AD, but the underlying molecular mechanisms are unclear. Considering that Alzheimer’s disease (AD) is a chronic disease progressing over a long period of time, even a slight increase of BACE1 expression may have a profound effect on Aβ accumulation.
BACE1 is the rate-limiting enzyme for amyloid-β peptides (Aβ) generation, a key event in the pathogenesis of Alzheimer’s disease (AD). Researchers report that the protein NRF2 decreases Bace1 mRNA and BACE1 protein levels, reduces amyloid-β plaques, and improves cognitive performance. In a mouse model of AD, ablation of the Nrf2 gene resulted in increased levels of Bace1 mRNA and BACE1 protein in brain tissues, increased amyloid-β plaque loads in the hippocampus and cortex of the brain, and increased cognitive impairment in a learning and memory test.
In 2 different mouse models of AD, treatment with the NRF2 activator sulforaphane, present in high amounts in vegetables such as broccoli and leafy greens, decreased Bace1 mRNA and BACE1 protein levels in brain tissues, reduced amyloid-β plaque loads in the hippocampus and cortex, and improved learning and memory performance in 2 behavioral tests.
According to the authors, the findings suggest that treatment with NRF2-activating plant compounds or synthetic small molecules could represent a potential therapeutic strategy for AD.
Ameliorating Alzheimer's disease in mice
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