Member
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Join Date: Apr 2016
Location: Australia
Posts: 352
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Member
Join Date: Apr 2016
Location: Australia
Posts: 352
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Alpha-synuclein mobilies inflammatory response to pathogens ...
In relation to Tupelo3's initial post,
from the research paper [1]:
"... alpha-syn is expressed during a GI infection and mobilizes an inflammatory response ..."
or, in the wording of the press release [2]:
"The nervous system within the wall of the GI tract detects the presence of a pathogen and responds by releasing alpha-syn. Alpha-syn then attracts white blood cells to the site where it has been released."
This raises an obvious question: What triggers the de-mobilization of the inflammatory response?
It seems to me that if the presence of alpha-syn mobilizes an inflammatory response, then the obvious trigger for de-mobilization would be the clearing of alpha-syn. If this is correct, this would seem to explain the long-term presence of neuroinflammation in PwPs. A lot of un-cleared alpha-syn is known to be present in the neurons of the substantia nigra (and other areas) in PwPs.
Why isn't the alpha-syn being cleared? Here are 3 possibilities (of course there are many more):
(1) A mutation in the SNCA gene causes alpha-syn to be modified in such a way that it cannot be cleared by the usual mechanisms. Kiwi33 has shown that this might be true in only a small number of cases (post #4).
(2) One or more viral/bacterial/fungal infections (perhaps a particular combination of them) somehow cause alpha-syn to be modified in such a way etc. etc.
(3) A mutation in one of the genes which control the protein-clearing mechanisms (ubiquitin/proteasome or lysosome/autophagy systems).
As I said in an earlier post, I think they are getting close now. Hopefully it will not be very long before we see a major breakthrough in the search for the primary cause of sporadic PD.
[1] Research paper: "A Role for Neuronal Alpha-Synuclein in Gastrointestinal Immunity", Stolzenberg et al., Journal of Innate Immunity, June 27 2017.
[2] Press release from Georgetown University: "Protein Associated with Parkinson’s Disease Linked to Human Upper GI Tract Infections", June 27 2017.
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