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 Defects of or related to agmatine transport causes dementia? 
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Joined: Mon Sep 30, 2013 11:16 pm
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Post Defects of or related to agmatine transport causes dementia?
A defect in or related to agmatine transport may be the cause of my disorder.

I previously posted on the over-expressed pathways that I thought were probably present in my disorder. These were presumed over-expression of pathways from:
1. Proline to ornithine decarboxylase to polyamines;
2. Arginine to NOS to NO to cGMP to cGMP dependent protein kinase; and
3. The urea cycle to creatinine.

I assumed that my arginase must be under-expressed because it leads from arginine to ornithine and citrulline (my ornithine and citrulline were low and on the low side respectively). Also, if my arginine is diverted away from the urea cycle to NOS as outlined above, it would follow that arginase is under-expressed. This is also pointed to by the borderline low urea/low urea that the disorder presents with when it is acute.

Thus, I was looking for a defect that would cause high ornithine decarboxylase activity, high NOS activity, high activity along the arginine to creatine pathway and low arginase activity. My reading of research is that agamatine/agmatine decarboxylase does all of this.

Agmatine is also an amine and I have food intolerance to amines. It is reported to cause diarrhoea and I have this. It is reported to be protective for lower back pain and neuro-protective and me and my father have/had lower back pain and pre-clinical, early onset symptoms of dementia and Parkinson’s, whilst my paternal grandmother had dementia and Parkinson’s. There is a suggestion that agmatine may be linked to rheumatoid arthritis which my father’s sister, who I am confident has the same disorder as me, also had.

I also suspect agmatine to be linked to G6PD via its reported connection to cGMP and thus to cGMP dependent protein kinase which is linked to G6PD. G6PD is strongly associated with psychosis, which my familial disorder presents with.

If I am right, how many more people have agamatine related disorders that have found expression in various disease states including dementia, I wonder.

I am not a doctor. The above is from memory. So please do not rely on it without properly verifying the information.


Mon May 26, 2014 5:42 am
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Joined: Sat May 25, 2013 3:53 pm
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Post Re: Defects of or related to agmatine transport causes demen
Thanks for sharing. You've obviously done a lot of research. Perhaps someone with the proper medical background will read this and be able to use the information. We'd all like to find a cure!

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Gail, Forum Moderator & daughter of Doris who passed away Dec. 2010 after living with LBD for 7 years.


Mon May 26, 2014 11:14 am
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Joined: Mon Sep 30, 2013 11:16 pm
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Post Re: Defects of or related to agmatine transport causes demen
Happy to. I worry that finding cures will take a long time if research continues to focus on finding one-size fits all tests and cures for diseases that probably have multiple causes. There should be people trained to do what I do for myself for everyone. Its a thought.


Mon May 26, 2014 6:04 pm
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Joined: Sun Mar 30, 2014 5:11 pm
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Post Re: Defects of or related to agmatine transport causes demen
Your research on this is impressive. What you're doing is contributing to the body of medical information and knowledge on dementia and related disorders. Hopefully, you and others can test some of these hypotheses you've presented and see what develops. I admire your perseverance!

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AnneA -- Forum Moderator; also daughter, caregiver, and patient advocate for Jean, who died of LBD in January, 2013, at age 91.


Wed May 28, 2014 12:09 am
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Joined: Wed Aug 06, 2008 2:24 pm
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Post Re: Defects of or related to agmatine transport causes demen
Thank you for sharing your thoughts on the underlying cause of your symptoms.

Given the complexity of your post, I have forwarded it to one of our scientific advisors for their feedback. I will contact you directly with additional information they provide via email.

I hope to be in touch soon!

Sincerely,
Angela

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Angela Taylor
Director of Programs
Lewy Body Dementia Association


Thu May 29, 2014 12:45 pm
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Joined: Mon Sep 30, 2013 11:16 pm
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Post Re: Defects of or related to agmatine transport causes demen
Thank you Angela and Anne,

I am very pleased that doctors/scientists may look at this.

Here is some more information that may assist them:

Cortisol is reported to stimulate up-regulation of a proline to ornithine to ornithine decarboxylase to polyamine pathway in pigs which results in high maltase (I have high maltase and repeat low ornithine). This is the paper that supports this: http://ajpendo.physiology.org/content/279/2/E395.

P5CR is the reverse of this pathway, so P5CR could be expected to be under-expressed. This would explain why mild or late onset P5CR disorder (caused by blocks in P5CR) type symptoms/conditions run in my family.

Incidentally, RU486, which the paper reports abolishes the cortisol stimulating effect in pigs, is mifepristone which is in late stage trials for psychotic depression.

I have drawn a diagram that shows the pathways and which would make it easier to follow. But I am not sure how easy it would be to upload to this site.

Best wishes and thanks again.


Sat May 31, 2014 6:12 am
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Joined: Sat May 25, 2013 3:53 pm
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Post Re: Defects of or related to agmatine transport causes demen
You can send an e-mail with an attachment ...

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Gail, Forum Moderator & daughter of Doris who passed away Dec. 2010 after living with LBD for 7 years.


Mon Jun 02, 2014 12:56 am
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