Volgens een hypothese (onderbouwde stelling) van Maes en Morris

spelen een toename van NF-kB en een afname van p53 een essentiële rol in ME/CVS,

o.a. omdat p53 mede de mitochondriale functie reguleert (aerobe/anaerobe stofwisseling).

Alhoewel in de studie zeer veel zinvolle constateringen de revue passeren,

wordt spijtig genoeg niet de link gelegd met de theorieën van prof. de Meirleir

(o.m. de negatieve correlatie tussen RNase-L-fragmentatie en p53, relatie met STAT-1).

Increased nuclear factor-κB and loss of p53 are key mechanisms in Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Med Hypotheses. 2012 Aug 27. doi:10.1016/j.mehy.2012.07.034.

Morris G, Maes M.

Abstract

Fukuda's criteria are adequate to make a distinction between

Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) and chronic fatigue (CF),

but ME/CFS patients should be subdivided into

those with (termed ME) and without (termed CFS) post exertional malaise [Maes et al. 2012].

ME/CFS is considered to be a neuro-immune disease.

ME/CFS is characterized by activated immuno-inflammatory pathways,

including increased levels of pro-inflammatory cytokines, nuclear factorκB (NF-κB) and

aberrations in mitochondrial functions, including lowered ATP.

These processes may explain typical symptoms of ME/CFS,

e.g. fatigue,malaise, hyperalgesia, and neurologic and autonomic symptoms.

Here we hypothesize that

increased NF-κB together with a loss of p53 are key phenomena in ME/CFS

that further explain ME/CFS symptoms,

such as fatigue and neurocognitive dysfunction, and

explain ME symptoms,

such as post-exertional malaise following mental and physical activities.

Inactivation of p53 impairs aerobic mitochondrial functions and

causes greater dependence on anaerobic glycolysis,

elevates lactate levels,

reduces mitochondrial density in skeletal muscle and

reduces endurance during physical exercise.

Lowered p53 and increased NF-κB

are associated with elevated reactive oxygen species.

Increased NF-κB induces the production of pro-inflammatory cytokines,

which increase glycolysis and further compromise mitochondrial functions.

All these factors together may contribute to mitochondrial exhaustion and

indicate that the demand for extra ATP upon the commencement of increased activity

cannot be met.

In conditions of chronic inflammation and oxidative stress,

high NF-κB and low p53 may conspire to promote neuron and glial cell survival

at a price of severely compromised metabolic brain function.

Future research should examine p53 signaling in ME/CFS.

PMID: 22951418

Key words:

Myalgic Encephalomyelitis (ME), chronic fatigue syndrome (ME/CFS), inflammation, cytokines, oxidative and nitrosative stress, cytokines, antioxidants