Unfolded Protein Response and A Possible Treatment for CFS

[aquariusgirl]

@mario Stephanie's seneff made the connection in that paper I sent u ..pirphyrins maybe?

 

[Bdeep86]

@aquariusgirl could I possibly get a copy of this paper?

 

[aquariusgirl]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392553/

 

[Bdeep86]

thank you

 

[mariovitali]

@aquariusgirl

Manganese could be an important factor (and Thank you for pointing this paper out) but the more i look into this, i more realize that we have to see this problem in a more Holistic way :

-Liver
-Bile Acids Homeostasis
-Mitochondria (perhaps NDUFS7)
-NR3C1
-Acetylation
-Methylation
-Manganese Levels
-Iron Levels
-Reasons for FXR/PXR dysregulation
...
...

IMHO We have to look at all of these Factors and take care of them one by one.

 

[aquariusgirl]

Yes .. I think the title of the paper is misleading . She talks about how heme dependent enzymes aren't working because of lack of heme & on & on

But Dr Shade says you have to shut down inflammation before you can detox & that feels right to me.

So you need Mn dependent SOD to work & you need. zinc & copper dependent SOD to work also .

Getting Zinc & Cu SOD working was crucial for me.

Also all the things you have brought up are pertinent for me ...dysfunctional iron & Cu metabolism. Lack of bile .. Misfolded proteins etc

 

[mariovitali]

@aquariusgirl

I think that our problem originates from Dysregulated Bile Acid intrahepatic circulation. Then it's all downhill from there, all systems are simply failing one-by-one : Acetylation, Phosporylation, Methylation, HPA Dysregulation,impaired Steroid and Neuro-steroid metabolism and Oxidative Stress, ...the icing on the cake is Liver and Mitochondrial Disease.

Uncontrolled Inflammation originates from impaired Liver function (my hypothesis)

 

[Bdeep86]

@aquariusgirl I also agree with @mariovitali however I will say that I believe manganese in the scheme of most talked about minerals is probably one of the more slept on minerals. I believe unbound iron and high levels of iron storage in soft tissues greatly antagonizes manganese in the system. Treating with a single mineral like manganese while the other systems Mario has pointed out are off balance you will ultimately setup a domino effect with other minerals and their co factors. I have seen this many times.

 

[Bdeep86]

@aquariusgirl I believe the foundation of this dysfunction is involved with copper/iron dysregulation. Its a bit complicated to convey over a message board but that will set the stage for these downstream effects. Mario believes there is an insult to the liver that damages it and set forth a dysfunction. I (at the moment) believe this is due to hepatic iron overload, this has yet to be substantiated.

 

[aquariusgirl]

Yes well iron & copper dysfunction will
Mess up your mito function fast.,,

They are chelating the iron out of the brains of Parkinsins patients & they have identified excess iron in brains of Alzheimers patients.

UCL London /UCLA

Also hyperoxoluria will take down sulfation ..so that as an impact on phase 2 liver enzymes

 

[aquariusgirl]

@Bdeep86 :what's the treatment? What are u doing ?

Drug companies are developing a bunch of new iron chelators fyi

 

[Bdeep86]

Yes your right on all of this @aquariusgirl you not only have copper not reaching cytochrome C oxidase, but you also have unbound iron inhibiting it as well.

 

[mariovitali]

@Bdeep86

Based on your Theory, what kind of test results on Iron and Copper should we expect to see (ie High Iron Levels, Low Copper etc)

 

[Bdeep86]

@mariovitali that is really a complicated question that maybe we can discuss the next time we speak as it would take me quite a bit of time to answer on here. One thing that i do routinely see is high levels of unbound copper. Not necessarily high readings of copper but high levels of unbound copper which can be found with a lab of copper and ceruloplasmin. @aquariusgirl did you have your copper and ceruloplasmin run is that why you suspect you have an issue with this?

 

[mariovitali]

@aquariusgirl

I think that our problem originates from Dysregulated Bile Acid intrahepatic circulation. Then it's all downhill from there, all systems are simply failing one-by-one : Acetylation, Phosporylation, Methylation, HPA Dysregulation,impaired Steroid and Neuro-steroid metabolism and Oxidative Stress, ...the icing on the cake is Liver and Mitochondrial Disease.

Uncontrolled Inflammation originates from impaired Liver function (my hypothesis)

@mariovitali that is really a complicated question that maybe we can discuss the next time we speak as it would take me quite a bit of time to answer on here. One thing that i do routinely see is high levels of unbound copper. Not necessarily high readings of copper but high levels of unbound copper which can be found with a lab of copper and ceruloplasmin. @aquariusgirl did you have your copper and ceruloplasmin run is that why you suspect you have an issue with this?

I see, and what about Iron Levels?

 

[Bdeep86]

@mariovitali thats the complicated part, would be easier to verbalize. I can try to write something.

 

[aquariusgirl]

@Bdeep86 .. No I kind of stumbled on it . I tried mitosynergys copper ...which is NOT regular copper which I assume would be pro oxidant or inflammatory & that was a revelation.

Then I noticed I had nickel adducts on SOD1 & I was SOD 2 +\+ so I assumed SODase was kaput.

I was terribly deficient in zinc but Mitosynergy copper was what made a huge impact.

The guy who created that is working on. A bioavailable form of iron ...,2 PhDs are on it they are .2 years out.

 

[aquariusgirl]

Check this out: I think proper copper & biotin have helped my mitos

http://m.jn.nutrition.org/content/137/1/25.full

This is a 2006 article from Bruce Ames & co which I thought was interesting.

Apart from the importance of biotin to mito function & in a further step heme synthesis, there is a really interesting throwaway line about how copper & biotin work together :



However, as expected from copper's role in complex IV, the recovery of complex IV was more efficient when copper and biotin were both added to the medium (data not shown).

 

[aquariusgirl]

I just saw some guidelines for Alzheimer's patients from UCLA & 1 recommendation was to balance copper & zinc.

But err no word on how to do that !!

 

[aquariusgirl]

@Bdeep86 ..no didn't discover it by testing more by accident after experimenting w/Mitosynergy copper!

I am SOD2 +\+ & I have nickel adducts on SOD 1 so it was a no brainer really but I suspect a familial problem w/copper