Yes. Please take a look at the following RG links.

Article The vermiform appendix impacts the risk of developing Parkin...

Article The appendix and the risk of Parkinson's disease: Appended n...

Yes. Please take a look at the following RG links.

Article The vermiform appendix impacts the risk of developing Parkin...

Article The appendix and the risk of Parkinson's disease: Appended n...

A recently published finding in Science Translational Medicine by Killinger was that people who had their appendix removed have an almost 20 percent lower risk of Parkinson’s, according to the study in , or a risk of 1.6 per 10,000 people over a decade compared to 1.98 in the general population.

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More frequent exposure to fungi in rural areas could account for the difference, as explained in the two comments above. This is especially significant for fungi that grow on farm crops, that may also be found in vegetable gardens.

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Note this coincidental finding about the appearance of Parkinson’s like symptoms in cows from eating corn with fungi:

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A tremorgenic mycotoxicosis of cattle caused by maize sprouts infested with Aspergillus clavatu. Onderstepoort J Vet Res. 1984 Dec;51(4):271-4.

An outbreak of disease affecting a herd of 16 dairy cattle which were fed mouldy, sprouted maize is described. Eight of the cattle were affected, 5 of which died. The clinical signs included muscular tremors, hypersensitivity, ataxia, anorexia and salivation. Aspergillus clavatus was the only fungus isolated from the sprouts. Clinical signs that were indistinguishable from those in the field outbreak were reproduced by dosing the mouldy maize sprouts to a steer and a sheep, and by dosing another sheep with maize inoculated with a pure culture of A. clavatus isolated from the mouldy maize on the farm. Light microscopical examination revealed neuronal degeneration and necrosis in the midbrain, medulla oblongata and spinal cord of all 3 of these animals. The disease is clinically and pathologically indistinguishable from the disease caused by the ingestion of sorghum beer residue, and in certain respects it is similar to toxicoses caused by the ingestion of wheat sprouts and malt sprouts infested with A. clavatus.

PMID: 6533519

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It’s also notable that aspergillus sp. produces large amounts of L-dopa, potentially explaining tremor symptoms as well as induction of negative feedback loop that could lead to shutdown of L-dopa production by brain cells.

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Production of L-dopa by Aspergillus terreus. FEMS Microbiol Lett. 1990 Oct;60(1-2):195-9.

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Biosynthesis of L-DOPA by Aspergillus oryzae. Bioresour Technol. 2002 Oct;85(1):25-9.17

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Aspergillus niger PA2: a novel strain for extracellular biotransformation of L-tyrosine into L-DOPA. Amino Acids. 2016 May;48(5):1253-62.

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Perhaps a-synuclein production follows a time-based route that coincides with migration of a fungi, starting at the appendix and Ending at the Brain, leading to early production at the starting location of the route and late production at the ending destination, so upregulation won’t be synchronous until the later stages of the migration. This chronological phenomenon would also explain the occurrence of PD later in life as a time vs distance phenomenon.

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Also notable that the migration could be facilitated by alternating states of the fungus between active and spore, with only one spore needed to seed the infection into nerve attached to gut, with the spore then activating to fully active organsim, then producing another spore than exits the neuron and crosses the synapse via exosomal movement.

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Parkinson’s disease; the hibernating spore hypothesis. Med Hypotheses. 2017 Jul;104:48-53.

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Perhaps the PD connection to the appendix is with undesirable organisms that reside in the appendix long-term and are never fully eradicated, in accordance with the antimicrobial activity for alpha synuclein observed in this study below. Higher levels of exposure to fungi in rural areas vs urban is consistent with this explanation.

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Functional characterization of alpha-synuclein protein with antimicrobial activity. Biochem Biophys Res Commun. 2016 Sep 16;478(2):924-8. “Here we demonstrate that α-Syn exhibits antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, we demonstrate a role for α-Syn in inhibiting various pathogenic fungal strains such as Aspergillus flavus, Aspergillus fumigatus and Rhizoctonia solani. We also analyzed localizations of recombinant α-Syn protein in E. coli and Candida albicans. These results suggest that in addition to α-Syn’s role in neurotransmitter release, it appears to be a natural AMP.” PMID: 27520375

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Finally, note that it might be significant for a-syncuclein to act as an antimicrobial/antifungal since there are 2 naturally occurring antifungal peptides, Cecropin (35 aa) and Dermaseptin (29 aa), that each have significant homology to the initial portion of a-synuclein. Cecropin has 25 identical or similar amino acids to the early portion of a-synuclein, while dermaseptin has 24 identical or similar amino acids to the same portion of a-synuclein.

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See Uniprot Align with pairing of P37840 with either P14666 or P84936 for verification.

Followers

Dear Arvind Singh

You suggested great articles again. I am thankful.

Dear Eli M Kammerman

Thank you so much for your valuable answer.

I think both articles are controversial, because firstly Parkinson's disease is genetically predisposed, and secondly, in my opinion, the symptoms of the disease are determined by how fast the degeneration of the enteric nervous system develops. This is confirmed by publications on N. vagus atrophy by ultrasound.

https://www.medicalnewstoday.com/articles/325152.php

perhaps you are interested in our PD model:

Noteworthy supporting reference:

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Alpha-synuclein in the appendiceal mucosa of neurologically intact subjects.

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Mov Disord. 2014 Jul;29(8):991-8.  Gray MT1, Munoz DG, Gray DA, Schlossmacher MG, Woulfe JM.

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Abstract

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We performed immunohistochemical staining for α-synuclein on gastrointestinal tissue from patients with no history of neurological disease using the established LB509 antibody and a new clone, MJFR1, characterized for immunohistochemistry here. We demonstrate that the vermiform appendix is particularly enriched in α-synuclein-containing axonal varicosities, concentrated in its mucosal plexus rather than the classical submucosal and myenteric plexuses. Unexpectedly, intralysosomal accumulations of α-synuclein were detected within mucosal macrophages of the appendix. The abundance and accumulation of α-synuclein in the vermiform appendix implicate it as a candidate anatomical locus for the initiation of enteric α-synuclein aggregation and permits the generation of testable hypotheses for Parkinson's disease pathogenesis.

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PMID: 24352892