Nrf2 Activation Prevents and Reverses Dementia in Conjunction with BDNF

Nrf2 sufficiency should reduce Alzheimer's disease.

Aging produces Nrf2 deficiency.

Nrf2 knock out mimic Alzheimer's APP and TAU protein aggregates.

Nrf2 deficiency allows protein aggregates to damage.  

Nrf2 sufficiency prevents damage, improves proteostasis and promotes autophagy to reduce the aggregates.

Remember that soluble beta amyloid induces oxidative stress, neutralized by Nrf2, that damages brain networks in Nrf2 deficiency.

Nrf2 can be stimulated by hydrogen rich water, sulforaphane, melatonin, wheat germ/spermidine and Green tea extract.

http://www.sciencedirect.com/science/article/pii/S2213231717303993

NRF2 deficiency replicates transcriptomic changes in Alzheimer's patients and worsens APP and TAU pathology

APP/TAU-induced oxidative and inflammatory stress is exacerbated by NRF2-deficiency.

Failure to translate successful neuroprotective preclinical data to a clinical setting in Alzheimer's disease (AD) indicates that amyloidopathy and tauopathy alone provide an incomplete view of disease. We have tested here the relevance of additional homeostatic deviations that result from loss of activity of transcription factor NRF2, a crucial regulator of multiple stress responses whose activity declines with ageing. A transcriptomic analysis demonstrated that NRF2-KO mouse brains reproduce 7 and 10 of the most dysregulated pathways of human ageing and AD brains, respectively. Then, we generated a mouse that combines amyloidopathy and tauopathy with either wild type (AT-NRF2-WT) or NRF2-deficiency (AT-NRF2-KO). AT-NRF2-KO brains presented increased markers of oxidative stress and neuroinflammation as well as higher levels of insoluble phosphorylated-TAU and Aβ*56 compared to AT-NRF2-WT mice. Young adult AT-NRF2-KO mice exhibited deficits in spatial learning and memory and reduced long term potentiation in the perforant pathway. This study demonstrates the relevance of normal homeostatic responses that decline with ageing, such as NRF2 activity, in the protection against proteotoxic, inflammatory and oxidative stress and provide a new strategy to fight AD.

Joseph Thomas (Tony) Liver