Unfolded Protein Response and A Possible Treatment for CFS

[mariovitali]

Are you able to get cannabidiol?

The type of ER stress caused by infiltration of viruses is what I am trying to figure out. When a virus has replicated all over your body how on earth to you get your body free of it if it's in the endoplasmic reticulum?

If ER stress caused by a drug can be relieved, and the remains of the drug removed, you will probably be more likely to retain your health improvement more easily than if there is a virus causing the stress. You may be very fortunate, hoping the best for you.

But I feel very fortunate that you brought your information here for expansion into the pathogen induced syndrome.

I think this is what causes the chronic fatigue syndrome. I am looking for an article that would explain how viruses in the ER cause lack of energy.

Do you know how ER stress causes OI? Maybe through neurodegeneration? Although it seems more easily reversible than something caused by neurodegeneration. That's another question that's in my mind this morning, and I will be looking around, but if you already have some specific information about that, I would appreciate it.

It seems as though ER stress is a cause of genetic mutations, have you found that conclusion in your reading?

I'm also wondering if since choline is an important remedial supplement for ER stress, and likewise for fatty liver, if the ER specifically has anything to do with fatty liver.

Maybe all these questions are already answered in this thread but I don't realize because when you don't know much about a subject you don't retain much of what you read. I'll go through the thread again. Your program generated lists will probably mean more to me this time around.

Another in depth educational article about endoplasmic reticulum.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666557/

As already discussed, i believe that CFS, Post-Finasteride syndrome and Accutane Permanent Side-Effects have the same basis.

The idea is that a virus or drug causes dysregulation on the ER and/or the Quality control of Protein folding also gets a hit. Then our bodies fall into a vicious cycle of continued ER Stress and UPR. This happens to us because of problematic SNPs (?) that have to do with Choline / BH4 / Methylation / Phenylalanine / TMAO levels (to name a few)

OI is caused i believe from ER Stress too. It's a dysautonomia which as an origin has ER Stress.

I am waiting for other member forums to test the regimen so i can say more. I have the impression that the implications of this regimen could be much more positive for us in the long run.

But first of all, we need to see that the theory is right.

 

[Violeta]

The idea is that a virus or drug causes dysregulation on the ER and/or the Quality control of Protein folding also gets a hit. Then our bodies fall into a vicious cycle of continued ER Stress and UPR. This happens to us because of problematic SNPs (?) that have to do with Choline / BH4 / Methylation / Phenylalanine / TMAO levels (to name a few)

Someone correct me if I'm wrong, but I think in the case of viruses, they are the proteins in the ER, they have the ability to hijack apoptosis, and since they inhibit the apoptosis of the cell, they multiply. That's why Epstein barr virus is found in certain types of tumors, the cells become immortal and tumors grow. I'm sure it can be explained more deeply than that, but not by me at this point.

Here's one bit of info on it.
http://www.hindawi.com/journals/av/2013/738794/

 

[mariovitali]

@Violeta

The Emerging Roles of Viroporins in ER Stress Response and Autophagy Induction during Virus Infection

Viroporins are small hydrophobic viral proteins that oligomerize to form aqueous pores on cellular membranes. Studies in recent years have demonstrated that viroporins serve important functions during virus replication and contribute to viral pathogenicity. A number of viroporins have also been shown to localize to the endoplasmic reticulum (ER) and/or its associated membranous organelles. In fact, replication of most RNA viruses is closely linked to the ER, and has been found to cause ER stress in the infected cells. On the other hand, autophagy is an evolutionarily conserved “self-eating” mechanism that is also observed in cells infected with RNA viruses. Both ER stress and autophagy are also known to modulate a wide variety of signaling pathways including pro-inflammatory and innate immune response, thereby constituting a major aspect of host-virus interactions. In this review, the potential involvement of viroporins in virus-induced ER stress and autophagy will be discussed.

 

[Gondwanaland]

I have questions about NAG...

Among all meds I took that impaired my gut health, the worst was Heparin. Immediately upon getting my 1st heparin shot I started having pain on my shoullders and arm and couldn't sleep on the side anymore. I am not sure what kind of pain it is, vascular or muscle, probably caused by induced low testosterone since heparin antagonizes vitamin K (Isuppose heparin mechanism is the same one as warfarin's). Recently I found this info

Heparin and inflammation: a new use for an old GAG?

(...) Heparin is a glycosoaminoglycan (GAG) formed by repeated sulphated oligosaccharide units.

(...) The anti-inflammatory activity of heparin has been reinforced by positive, although small, clinical trials in patients suffering from a range of inflammatory diseases, including rheumatoid arthritis.

One question is if NAG would have undesired hormonal or neurotransmitter side-effects...

Other question is why did DH had a terrible knee, shin/calf pain and then swollen ankle after taking 250mg of NAG today... I suspect lymphatic system...

 

[JaimeS]

@mariovitali - here is the first blog post in my series about understanding SNPs. If you understand it all, just scroll down to the bottom of the blog and hit the next button for the next one. I believe I ended up breaking it down into four posts.

It takes some work to determine the likelihood that a SNP will be pathogenic...

http://forums.phoenixrising.me/inde...ndme-and-the-information-overload-of-me.1759/

....but starting here might be more pertinent to your question, and you can always go back as well as forward if you feel like you've been thrown into the deep end:

http://forums.phoenixrising.me/index.php?entries/part-iii-dealing-with-your-rarer-snps-1-of-2.1761/

-J

 

[ppodhajski]

I have questions about NAG...

Among all meds I took that impaired my gut health, the worst was Heparin. Immediately upon getting my 1st heparin shot I started having pain on my shoullders and arm and couldn't sleep on the side anymore. I am not sure what kind of pain it is, vascular or muscle, probably caused by induced low testosterone since heparin antagonizes vitamin K (Isuppose heparin mechanism is the same one as warfarin's). Recently I found this info

Heparin and inflammation: a new use for an old GAG?

One question is if NAG would have undesired hormonal or neurotransmitter side-effects...

Other question is why did DH had a terrible knee, shin/calf pain and then swollen ankle after taking 250mg of NAG today... I suspect lymphatic system...

Regarding Heparin: "The first is elevation of serum aminotransferase levels, which has been reported in as many as 80% of patients receiving heparin" So I would start looking there, sounds like Heparin messes with the liver.
https://en.wikipedia.org/wiki/Transaminase

As for N-Acetyl Glucosamine, I personally do not think it helps cure anything, but it is more like a drug. I personally always favor taking only cofactors. But saying that, glucosamine is produced by Glutamine—fructose-6-phosphate transaminase. Note the transaminase and my remark on Heparin above. Does DH have diabetes or take wafarin?

 

[Gondwanaland]

Does DH have diabetes or take wafarin?

He doesn't, but he is a sugar addict with insulin resistance.

Thanks for those hints, @ppodhajski

 

[Gondwanaland]

As for N-Acetyl Glucosamine, I personally do not think it helps cure anything, but it is more like a drug. I personally always favor taking only cofactors. But saying that, glucosamine is produced by Glutamine—fructose-6-phosphate transaminase.

NAG is recommended for oxalate issues... Interesting bit of info re Glutamine, thanks!

 

[mariovitali]

@Gondwanaland

Please note that at my original post of this thread i've warned that you shouldn't drink NAG along with Sugar. I had symptoms whenever this was happening...

 

[Gondwanaland]

@Gondwanaland

Please note that at my original post of this thread i've warned that you shouldn't drink NAG along with Sugar. I had symptoms whenever this was happening...

I know, I took note of that, it's just I that I thought I could keep him off of sugar today
Thanks for the reminder anyway, mario

 

[mariovitali]

@Gondwanaland

No problem, i guess you could start the regimen slowly by adding the supplements one by one and taking note of the progress/symptoms.

Good Luck to DH and you

 

[Violeta]

OI is caused i believe from ER Stress too. It's a dysautonomia which as an origin has ER Stress.

Some ideas about OI. They don't mention ER stress, but you can see that some of the things that they say cause it obviously are ER stressors.

http://www.wellnessresources.com/he...ps_pots_chronic_fatigue_autoimmune_disorders/

 

[mariovitali]

@ppodhajski @Violeta


Here are the results from adding thioredoxin reductase to the list of Topics that are being analyzed. Very interesting indeed.

Look how the algorithm reveals *possible* associations between the different topics (among 192 Topics in total):

So it appears that associations exist between hsp70,ros,upr,oxidative stress protection,sirt1 and selenium deficiency

Very good addition @ppodhajski ! Yet one more *possible* reason for having selenium added to the regimen.

I will add FADS1 and FADS2 to the list of Topics under consideration. Each run takes -unfortunately- 4 hours to complete...

 

[mariovitali]

@Violeta

Here is a run for Orthostatic Intolerance :

There is an association between Panic disorder and OI because OI is frequently misdiagnosed as Panic Disorder. Look however on the fact that adrenergic receptor appears frequently. So here is a run for adrenergic receptor :

Look how often atrial fibrillation, acetylcholine and sshl (Sensorineural Hearing Loss) appear within the results. Note also that i had 4-5 incidences of SSHL (you can search my posts for details). I then search for SSHL and adrenergic receptor on Google :

One hypothetical scenario in ISSHL is a sudden reduction of the blood flow in the labyrinthic artery, which is a functional end artery. The blood flow in the labyrinthic artery is regulated mainly by adrenergic receptors on smooth muscle cells. It is also influenced by plasma viscosity and local regulatory mechanisms, but not by central regulatory mechanisms as in larger vessels. Due to the possible ischemia-like cause of ISSHL, it was hypothesized that risk factors, comparable to those associated with ischaemic or thromboembolic diseases, such as heart disease, stroke and thrombosis [11]–[13], may play an underlying role in disease-aetiology. However, these studies were not conclusive and, in part, contradictory[14], [15]. The strongest argument for a vascular or haemorheological origin of ISSHL is the observation that outcome is significantly improved in ISSHL patients who underwent combined LDL and fibrinogen apheresis [16]. Because raised fibrinogen and LDL cholesterol-levels are risk factors for such vascular diseases as ischaemic heart disease, stroke and other thromboembolic diseases [17], [18], this observation supports the idea that the aetiology of ISSHL is vascular.

 

[ppodhajski]

Great stuff @mariovitali

On OI, I used to have it bad. My blood pressure would shoot up, as would my heart rate, when I would stand. I also had anxiety disorder. And I most definitely think both OI and anxiety disorder share the same root cause. I do not think it is misdiagnosis, I think it is comorbid. (I used to say to doctors; "Yes, it is in my head, and it is in my body as well.)

My theory on OI is that we either get rid of norepinephrine too slowly (me) or too quickly (people who get low blood pressure when they stand up.) A few of my norepinepherine transpoprter SLC6A2 SNPS are rare (That gene is also associated with ADD) and my MAOA, MAOB, and COMT genes are slow.

The research definitly shows a link between norepinepherine and OI.
http://circ.ahajournals.org/content/99/13/1706.full

And Monoamine Oxidase
http://www.ncbi.nlm.nih.gov/pubmed/1007896

I think another thing you need to add are all the receptor and transporter genes for the neurotransmitters. For my self I know that my serotonin transport genes are "long form" (SLC6A4), some of my serotonin receptor SNPs are rare (HTR2A HTR3B HTR3C)

I am a VERY sensitive person when I do not have my Riboflavin.

But there are adrenal receptors, dopmaine receptors and transporters, etc That is the triangle: release, receptor, and transport.

 

[mariovitali]

Great stuff @mariovitali

On OI, I used to have it bad. My blood pressure would shoot up, as would my heart rate, when I would stand. I also had anxiety disorder. And I most definitely think both OI and anxiety disorder share the same root cause. I do not think it is misdiagnosis, I think it is comorbid. (I used to say to doctors; "Yes, it is in my head, and it is in my body as well.)

My theory on OI is that we either get rid of norepinephrine too slowly (me) or too quickly (people who get low blood pressure when they stand up.) A few of my norepinepherine transpoprter SLC6A2 SNPS are rare (That gene is also associated with ADD) and my MAOA, MAOB, and COMT genes are slow.

The research definitly shows a link between norepinepherine and OI.
http://circ.ahajournals.org/content/99/13/1706.full

And Monoamine Oxidase
http://www.ncbi.nlm.nih.gov/pubmed/1007896

I think another thing you need to add are all the receptor and transporter genes for the neurotransmitters. For my self I know that my serotonin transport genes are "long form" (SLC6A4), some of my serotonin receptor SNPs are rare (HTR2A HTR3B HTR3C)

I am a VERY sensitive person when I do not have my Riboflavin.

But there are adrenal receptors, dopmaine receptors and transporters, etc That is the triangle: release, receptor, and transport.

The knowledge you share with us is really helpful, Thanks @ppodhajski !


Could you please provide a list of Genes (rs numbers and associated SNPs) that we should look at? I am not that knowledgeable in this area (Gene + SNPs) i only know how to use Promethease with my 23andme data. That's all!




Thank you in advance!

 

[ppodhajski]

The knowledge you share with us is really helpful, Thanks @ppodhajski !

Could you please provide a list of Genes (rs numbers and associated SNPs) that we should look at? I am not that knowledgeable in this area (Gene + SNPs) i only know how to use Promethease with my 23andme data. That's all!

Thank you in advance!

I have a list but I want to add some new stuff to it. I will post it when I am done. But here is a chart (attached) I made of most of the pathways I look at, it is just missing the Fatty Acid Pathways

 

[Violeta]

I definitely saw that lipids are made in one type of ER,

"whereas active smooth endoplasmic reticulum lacks ribosomes and functions in lipid metabolism, carbohydratemetabolism, and detoxification[citation needed] and is especially abundant in mammalianliver and gonad cells. "

and there is this source that says that fatty acids are elongated in the ER,
http://library.med.utah.edu/NetBiochem/FattyAcids/6_2a.html

but I don't know if that means that all fatty acids or just new fatty acids are processed in the ER.

 

[Violeta]

There is an association between Panic disorder and OI because OI is frequently misdiagnosed as Panic Disorder. Look however on the fact that adrenergic receptor appears frequently. So here is a run for adrenergic receptor :

What do you suppose is wrong, adrenergic receptor error, or neurotransmitter deficiency?

 

[mariovitali]

What do you suppose is wrong, adrenergic receptor error, or neurotransmitter deficiency?

I believe that Adrenergic receptor had definitely something to do with a lot of symptoms such as OI, Irregular Heartbeat and GI problems to name a few. The mechanism with which it is affected is a big question.

Another really interesting fact that i experienced during my recovery : The Reversal of symptoms! So what does that mean. In a nutshell, here is the ORDERED list (roughly) of the symptoms i experienced when i crashed from Finasteride :


1) Urticaria
2) GI Problems (mainly spasms in my esophagus)
3) Joint Pains
4) Neurological Pains
5) Insomnia
6) RLS
7) OI
....


So when recovery has started symptoms began vanishing from the bottom to the beginning so (in reverse order) :

-First OI was resolved
-Then RLS
-Then Insomnia
-Then Neurological Pains


...and so on. Crazy right? Yes i know....


As soon as there are individuals that will try the regimen and start getting better only then i will tell more things that i noticed but for now i will keep them for myself.

I don't want any Men in white coming here and start banging at my door!