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

Improve Diabetes and Bipolar Diseases With Increased Net Total Antioxidant Capacity

Diabetics on insulin are controlled (not cured) but have impaired thioredoxin (and increased TXPIN.)

Manic patients on therapy are controlled (not cured) but have impaired thioredoxin (and increased TXPIN.)

BOTH have either/or both increased oxidative stress or reduced antioxidant capacity.

Could we improve control in both of these "metabolic illnesses?"

How.

1.  Control of symptoms and consequences.  Normalize affect and elevated glucose.

2.  Increase net total antioxidant CAPACITY by activating the Nrf2 pathway with hydrogen rich water, sulforaphane, melatonin and wheat germ in conjunction with 12 hours of daily fasting, four minutes of Tabata high intensity interval exercise and two minutes of slow paced breathing twice daily.

Level of plasma thioredoxin in male patients with manic episode at initial and post-electroconvulsive or antipsychotic treatment

http://onlinelibrary.wiley.com/doi/10.1111/pcn.12244/full

Klotho AND Nrf2 for Health and Wealth

Klotho gene acts by activating Nrf2 pathway negating angiotensin 2 related oxidative stress.

Sulforaphane, hydrogen rich water and melatonin activate Nrf2.

Green tea extract reduces Keap1, the antagonist for Nrf2.

Klotho variant improves longevity and IQ by making GluN2b more sensitive to BDNF.

BDNF activity is inversely related to depression and suicide.

BDNF is directly related to school performance, life success and metabolic cell health.

Would Sulforaphane, hydrogen rich water, melatonin and green tea extract improve the following?

School performance.

Life performance.

Metabolic health and tissue and organ function.

Depression.

Suicide.

How much?

Targeting Klotho (for GluN2b) AND Nrf2 (for BDNF and reduced oxidative stress, gene repair and epigenetic gene expressing restoring.)

Healthy kidneys express Klotho which targets the hippocampus GluN2b expression upon which BDNF works.

The anti-ageing hormone klotho induces Nrf2-mediated antioxidant defences in human aortic smooth muscle cells

http://onlinelibrary.wiley.com/doi/10.1111/jcmm.12996/full