Neuronal Alpha-Synuclein in Gastrointestinal Immunity - upper GI tract infections

[aspergerian]

Protein associated with

Parkinson's disease linked to human upper GI tract infections.

sciencedaily.com/releases/2...

A Role for Neuronal Alpha-Synuclein in Gastrointestinal Immunity.

karger.com/Article/FullText...

[jeffreyn]

Hi aspergerian,

I did a post about this research paper yesterday, but that's okay, now it's twice as likely that people will become aware of it.

But it was actually Tupelo3 over at NT who beat us both to the punch. Here is my reply to his post. What do you think?

Jeff

------

I'd like to make a couple of points regarding the research paper.

"the discovery reported here extends the hypothesis of Braak et al. that PD begins in the ENS by proposing that PD results from the excessive response of a normal innate immune component of the ENS"

I think they are almost there, but something is still missing. Otherwise every kid who got lots of viral infections of the GI tract would end up getting PD later in life.

"Since it is known from genetic studies that individuals with multiple copies of alpha-syn invariably develop PD, an increase in the expression of alpha-syn is sufficient to cause PD."

I think "invariably" is incorrect - I think the correct figure is less than 100% [1]. Also, there is a basic error of logic in this sentence. Even if 100% is the correct figure, an increase in the expression of alpha-syn is not necessarily sufficient to cause PD. It might also require the presence of, say, a second mutation, which has not yet been identified.

Back to my first point. Perhaps the "something" that is still missing is indeed a genetic mutation, which prevents alpha-syn from being cleared in the usual way.

I acknowledge that it seems unlikely that such a mutation, if it exists, would not have already been identified.

​

[1] Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease, Polymeropoulos et al., Science. 1997 Jun 27;276(5321):2045-7.

[QNTT in reply to jeffreyn]

what is "NT" ?

[jeffreyn in reply to QNTT]

NT is NeuroTalk. It's one of the other forums out there. It's a bit like HU.

[QNTT in reply to jeffreyn]

So That's where you go and get ideas eh ?

And then you come here and sound like smartY pantS

Oh I KID Jeffreyn with luv !

a-Synuclein references are never enough, aS is becoming more than hypothesis, its establishing itself as The Target for PD.

If you read here, you must know by now that GM1 is my favorite, but we are not getting that, sadly.

Second favorite are the 2 vaccines aimed against aS the Austrians and Irish are trialing.

But nature has its way, and there is no rule that says human logic must pan out. So I am for what works, to put a stop at least to PD, but in our life times, will you Big Pharma? I can dream can I ?

[aspergerian]

Jeffrey,

Sorry I missed your original post on the new innate-immunity

alpha-synuclein study. As a model, might we consider that (a) some

cases of PD are induced by a predisposing allele affected by one or

several environmental factors (1), and (b) some cases may be induced

by a conjunction of more than several environmental even in the

absence of PD-risk variants? For instance, speculatively, if 5-7,

nearly simultaneous environmental factors occurred in an individual,

then his or her physiology might initiate first stages of PD. A

multi-hit model could lead to the 1% figure. Braak has moderated his

stages (2).

Expecting company, gotta hobble off.

1. Here's a PD risk variants summary:

snpedia.com/index.php/Parki...

Many SNPs have been reported to be associated with risk [for PD],

but few have shown significant odds or have been robustly

replicated. And as a 2016 editorial succinctly puts it, as for many

other disorders, the genetic risk factors for Parkinson's disease

can be roughly divided into three categories as follows: [1]

Mutations that lead to Parkinson's in nearly everyone who carries

one. This is the smallest group, and people with these mutations

usually have either a strong family history and/or a very early

onset of the disease, i.e. in their twenties or thirties. At this

time, only certain mutations in the LRRK2, SNCA, and TMEM230 genes

appear to be causative for clinically typical and Lewy

body–confirmed Parkinson's disease. [2] Risk factors that

significantly increase the risk of Parkinson’s (e.g., by 10-fold

compared to the general population). However, note that many, if not

most, of the carriers of these risk factors will never develop the

disease. [3] Variants that slightly increase Parkinson’s risk (up to

two-fold in most cases). These variants are very common world-wide,

with many of them present in 20-40% of the healthy population and

none of whom will ever develop the disease. Only some abnormally

high accumulation of such variants, and/or interaction with

particular environmental factors, would actually lead to to

Parkinson's.

2. Neuropathological Staging of Brain Pathology in Sporadic

Parkinson's disease: Separating the Wheat from the Chaff.

ncbi.nlm.nih.gov/pubmed/282...

.