Deb,

I don't have a direct answer to your question, but is there a way to slow defensin  5 alpha catabolism, or at least a way to stabilize it, in addition to helping the body make it?

TMD

I think with ALS the body is already trying to do that.  There is a problem with protein digestion and I think that's the body's response to reduce breaking down the defensin 5 alpha, the body makes less protein digestive enzymes.

Hi Deb,  I am deeply impressed with your intellectual pursuit on this problem.

Although I have a severe lack of knowledge at the chemical process level I was wondering if an overview of digestive enzyme supplements might offer some insight.  I remember that papaya fruit is used to marinate meat, and has an digestive role ( as an enzyme I believe ).  It might be useful if anyone has looked at the incidence rate of ALS in populations that have a natural intake of any digestive supplement (such as papaya).

I also have to wonder if anyone has pursued any therapy for ALS involving digestive enzymes.

All the best 

Greg Z.

I know of people having digestive enzyme support with the disease and a woman I know who managed to keep her son alive for 13 years that insists that all ALS patients need this kind of support and that they lack protein digestion.  So, they can be given protein digestion support, but the thing that the leaky gut study is showing is a reduction in the production of the defensin 5 alpha which is leading to the shift in the microbiota.  I wonder if there might be a blockage for releasing the defensin 5 alpha as something I read seemed to suggest there wasn't anything wrong with production.  So then even another question could be is there something that is breaking it down.  It wouldn't be the body's own enzymes because they are reduced.

Hi Deb

Came across a couple of items which may be of some interest.

http://medicalxpress.com/news/2016-04-immune-system-proteins-giveth-taketh-motor.html

Another couple of articles

http://medicalxpress.com/news/2016-04-central-nervous-inflammationa-pathway-drug.html

Interesting, what that first article is indirectly saying is that you have more of the MHCI complex, you are going to have more pruning of neurons to muscles, and to turn that down, you have higher risk for infections, and ALS patients already have a high risk for infections.

Zonulin (ZO)-1 protein which reduces gut permeability....

http://medicalxpress.com/news/2016-04-coffee-consumption-effect-non-alcoholic-fatty.html?utm_source=nwletter&utm_medium=email&utm_content=ctgr-item&utm_campaign=daily-nwletter

Thanks Gregory.  

33.

Efficient production of a soluble fusion protein containing human beta-defensin-2 in E. coli cell-free system.

Chen H, Xu Z, Xu N, Cen P.

J Biotechnol. 2005 Feb 9;115(3):307-15.

PMID:

 15639093

Similar articles

Select item 15327366 34.

Preferential codons enhancing the expression level of human beta-defensin-2 in recombinant Escherichia coli.

Peng L, Xu Z, Fang X, Wang F, Yang S, Cen P.

Protein Pept Lett. 2004 Aug;11(4):339-44.

PMID:

 15327366

Similar articles

Select item 14619561 35.

FYI - article production of beta-defensin-2

might be useful to contact  

You have given me enormous information to integrate into what I am trying to understand, so I read this the day you posted, and where it lead me in terms of researching is interesting.  beta-defensin-2 is a skin anti-microbial peptide and often when we try something to try and help her, she breaks out in hives.  

The body is trying to help itself and it uses the skin, stools and urine to eliminate the bad "stuff."  So, that she breaks out in hives when we try something that is suppose to help her body to eliminate toxins suggests that she also has an unidentified problem here and now I wonder if there is also a problem with levels of this antimicrobial peptide in ALS and perhaps other disease and in particular psoriasis types of diseases.

Hi Deb:

I would tend to wonder if there is a relatively simple epigenetic change that results in a deficient process of protein synthesis - and if it might be common to the production of all defensins - I wonder if anyone has investigated the DNA and RNA coding for defensin production in healthy people.  With use of CRISPER substitution it may then be a simple substitution....  I would look to any survey of the genome referring to defensin synthesis - maybe Celera Genomics would have some insight.

I imagine almost any virus or bacteria or toxin could change gene expression,  Craig Venter of Celera was doing a survey of ocean organisms.

Hope some of this is of help and not just leading in the wrong direction.

I could easily believe defensins are essential to prevent premature aging in any system....

http://www.pbs.org/wgbh/nova/next/evolution/crispr-gene-drives/

"Most natural gene drives are picky about where on a strand of DNA they’ll cut, so they need to be modified if they’re to be useful for genetic engineering. For the last few years, geneticists have tried using genome-editing tools to build custom gene drives, but the process was laborious and expensive. With the discovery of CRISPR-Cas9 as a genome editing tool in 2012, though, that barrier evaporated. CRISPR is an ancient bacterial immune system which identifies the DNA of invading viruses and sends in an endonuclease, like Cas9, to chew it up. Researchers quickly realized that Cas9 could easily be reprogrammed to recognize nearly any sequence of DNA. All that’s needed is the right RNA sequence—easily ordered and shipped overnight—which Cas9 uses to search a strand of DNA for where to cut. This flexibility, Esvelt says, “lets us target, and therefore edit, pretty much anything we want.” And quickly."

Funny you should mention viral agents...  I am wondering herv-k is somehow doing this.   I am strongly believe that herv-k is playing a serious role in ALS, but research seems to be directed almost exclusively to how it is involving RNA transcription around misfolding with TDP-43 and mutations or something like that.

TDP-43 was first found as something that regulated HIV, so I've posted my question about whether the body is having a problem with it because of an overproduction to have to regulate herv-k.

And then there is a paper on C4 and schizophrenia that does an excellent job of sorting out different C4 genes and they found increased herv-k could be correlated with gene expression, but I think attributed the increased expression to the actual herv-k and I questioned if complement evasion with C4b binding strategies would also do the same thing.

And the altered microbiome...  I think quite possibly a lot more biotoxins being produced.  My poor dear sister has ongoing brain fog that is so bad she finds having to concentrate to read enormously tiring and challenging.

Your suggestions are going over my head as I haven't a clue of how I would follow up on those suggestions.

https://www.researchgate.net/post/In_ALS_is_TDP-43_is_it_being_produced_to_control_herv-k

Article Schizophrenia risk from complex variation of complement component 4

http://medicalxpress.com/news/2016-04-pollutants-fish-inhibit-human-natural.html

Article - pollutants in fish may be disabling immune system function - does not specify which part - but might provide some insight

http://medicalxpress.com/news/2016-04-pandemic-coli-strain-h30-cloaks.html?utm_source=nwletter&utm_medium=email&utm_content=ctgr-item&utm_campaign=daily-nwletter

References E. coli H30 - extremely efficient pathogen

Just found an answer...  https://www.researchgate.net/publication/309335976_a-Defensin_5_gene_expression_is_regulated_by_gut_microbial_metabolites

Article α-Defensin 5 gene expression is regulated by gut microbial metabolites