Gut Instinct

[imshakydad]

my latest pd post fyi

imshakydad.wordpress.com/20...

[jimcaster]

Very good summary of the research related to the gut-brain connection in PD.

[Rhyothemis]

I think one of the most interesting pieces of information I’ve learned about PD is that in epidemiological studies, appendectomy is associated with reduced risk of developing PD:

nih.gov/news-events/nih-res...

‘The team also found a build-up of the toxic form of alpha-synuclein in the appendixes of healthy volunteers. This suggests that the appendix may be a reservoir for the disease-forming protein and may be involved in the development of Parkinson’s disease.

“We were surprised that pathogenic forms of alpha-synuclein were so pervasive in the appendixes of people both with and without Parkinson’s. It appears that these aggregates—although toxic when in the brain—are quite normal when in the appendix. This clearly suggests that their presence alone in the gut cannot be the cause of the disease,” Labrie said.’

[MarionP in reply to Rhyothemis]

And we know for a fact that the reverse is not possibly the case, that for some reason the appendix is a sort of protective prison for the toxic alpha synuclein so that it doesn't affect the brain? What is the basis for assuming anything, much less the one preference over the other? Would be nice to know more about which direction is the lean.

Also: new research out on flu virus strains that kill off i widespread fashion substanta nigra dopamine producing cells.

the-scientist.com/features/...

[Rhyothemis in reply to MarionP]

It would seem that formation of misfolded a-syn in the appendix is not sufficient by itself - that there has to be some other factor that results in the propagation of a-syn.

One thing I would like to know is if there are multiple forms of misfolded a-syn, and if that was a difference between the PD group and the healthy group. A-syn from PD differs from a-syn in MSA - the latter is able to cause prion-like transmission:

ncbi.nlm.nih.gov/pubmed/288...

The appendix is kind of a toxic prison - a panopticon for toxins and pathogens. It functions as part of the immune system and is responsible for surveillance of pathogens and toxins. It is also thought to serve as a reservoir of gut microbes for re-population of the gut after really bad GI infections.

ncbi.nlm.nih.gov/pubmed/153...

onlinelibrary.wiley.com/doi...

[MarionP in reply to Rhyothemis]

Good stuff Rhyo!

[Rhyothemis in reply to MarionP]

Glad you liked it... but I neglected to really consider the reverse-causation angle. It is possible that whatever it is that predisposes people to acute appendicitis (leading to appendectomy) is also protective against PD.

A study found an inverse association between appendicitis and ulcerative colitis, and the study authors postulated that "genetic or environmental factors linked to an increased risk of appendicitis while being protective against UC may explain the repeatedly reported reduced relative risk of UC in individuals with a history of appendicitis".

ncbi.nlm.nih.gov/pubmed/271...

So perhaps that is what is going on with PD risk and acute appendicitis/appendectomy.

[Rhyothemis in reply to Rhyothemis]

Came across this in the Science of Parkinson's Blog 'March News' post:

Lipopolysaccharide from Gut Microbiota Modulates α-Synuclein Aggregation and Alters Its Biological Function

pubs.acs.org/doi/10.1021/ac...

Leaky gut = higher serum LPS

[MarionP in reply to Rhyothemis]

Wow...all I can say is wow.

Serum means to me that there is another way than just flu virus that kills dopamine and other brain cells travelling the vagus nerve up into the brain, bad LPS can get into the bloodstream, maybe mess with muscles. Wonder if it can pass the blood brain barrier.

But I have yet to actually read the paper, will do that if I can get into it.

[Hidden in reply to MarionP]

Yes, LPS can definitely disrupt the blood brain barrier!

Art