Re: TGF-beta1 in CFS impairs NRF2-ARE Phase II detox - supressing glutathione

Nrf2 protecting against glutamate toxicity, neuroprotective

"The Nrf2-ARE pathway appears to contribute to neuroprotection. First, activation of the Nrf2-ARE pathway by tert-butylhydroquinone (tBHQ) protected neuroblastoma cells from oxidative glutamate toxicity (27)"

"Overexpression of Nrf2 and small molecule-mediated activation of the Nrf2-ARE pathway in astrocytes increased resistance of neurons to non-excitotoxic glutamate toxicity (31)"

NRf2 - A multi-organ protector?

List of Nrf2-ARE inducers

Nrf2-ARE Inducers

Some of the most potent ones:

purpurogallin methyl carboxylate black tea

carnosic acid diterpene rosemary, sage

3H-1,2-dithiole-3-thione (D3T) dithiolethione Brussels sprouts, cabbage

quercetin flavonol capers, lovage, radishes, dill, cilantro, fennel leaves, red onion

curcumin polyphenol turmeric

sulforaphane isothiocyanate broccoli sprouts, broccoli, cabbage, brussels sprouts

fisetin flavonol strawberries, apples, Japanese wax tree

kahweol diterpene coffee

cafestol diterpene coffee

Could Nrf2 inhibition explain heart rate variability issues in CFS?

The influence of nrf2 on cardiac responses to environmental stressors.

Hypoxia and particulate matter caused more heart rate variability in Nrf2 knockout mice.

Could this help to explain the chronic heart rate variability issues in CFS, if CFS patients have Nrf2 inhibited for some reason (HSP, genetics, mold toxins, etc.)?

"Results demonstrate that Nrf2 deletion increases susceptibility to change in HR and HRV responses to environmental stressors and suggest potential therapeutic strategies to prevent cardiovascular alterations."

Histone deacetylase elevation and oxidative stress, decreased glucocorticoid activity in CFS/ME

An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Decreased glucocorticoid sensitivity and high oxidative stress in CFS might be related to histone deacetylases (HDACs),

HDACs need to be inhibited in order for Nrf2 to be recruited.

HDACs can also promote pro-inflammatory gene expression. This could account for more expression of IL-8, which then suppresses cortisol production.

Jason, Sorenson et al. (2011) found that elderly people with CFS/ME had elevated HDAC activity.

HDAC activity could lead to a chronic pro-inflammatory state that leads to fatigue.