Abstract

The cellular hallmarks of Parkinson’s disease (PD) are the loss of nigral dopaminergic neurons and the formation of α-synuclein-enriched Lewy bodies and Lewy neurites in the remaining neurons. Based on the topographic distribution of Lewy bodies established after autopsy of brains from PD patients, Braak and coworkers hypothesized that Lewy pathology primes in the enteric nervous system and spreads to the brain, suggesting an active retrograde transport of α-synuclein (the key protein component in Lewy bodies), via the vagal nerve. This hypothesis, however, has not been tested experimentally thus far. Here, we use a human PD brain lysate containing different forms of α-synuclein (monomeric, oligomeric and fibrillar), and recombinant α-synuclein in an in vivo animal model to test this hypothesis. We demonstrate that α-synuclein present in the human PD brain lysate and distinct recombinant α-synuclein forms are transported via the vagal nerve and reach the dorsal motor nucleus of the vagus in the brainstem in a time-dependent manner after injection into the intestinal wall. Using live cell imaging in a differentiated neuroblastoma cell line, we determine that both slow and fast components of axonal transport are involved in the transport of aggregated α-synuclein. In conclusion, we here provide the first experimental evidence that different α-synuclein forms can propagate from the gut to the brain, and that microtubule-associated transport is involved in the translocation of aggregated α-synuclein in neurons.


http://link.springer.com/article/10....401-014-1343-6

http://www.news-medical.net/news/201...-research.aspx

I take this as supporting the theory that PD begins in the gut. Why, I am not sure, although I am leaning towards the notion that unhappy gut flora, in attempts to stabilize/balance/get the environment where they need it to be, mutate things including alpha-synuclein.

We have no idea, really, of what all the different type of microflora that make up our biomes are, much less the healthy ratio of what they should bear to each other. I would suspect that our individual gut microbiomes are as unique as we are.

I guess this means we keep juicing, eating as healthy as we can in between, exercising, and enjoying life as much as possible. As the man in "Fat, Sick, and Nearly Dead" said, we need to make health the priority, not wealth. So true.

I believe you are correct in considering disturbed gut flora (dysbiosis) as the culprit. A year ago I listened to a health program called "The People Pharmacy" where the guest was a gastro-interologist discussing the important role that a healthy human microbiome plays in ones health. His discussion was mainly about how fecal implants/transplants that are being done on people that have severe health problems in the gut, primarily C. difficile infections which are life threatening, with great success. He also mentioned that the fecal implants were being done by
patients with crohns disease as well as PWP, also showing efficasy. Dr Thomas Barody in Sydney Australia, a pioneer in this therapy, is also getting positive results. He calls his therapy "Human Probiotic Infusion". I know I personally suffer frow dysbosis as a result of broad spectrum antibiotic use given to me by my dermatologist to treat back acne. I took another round of Antibiotics in my early 20's, destroying my gut flora from which my microbiome never recovered. Gut flora exist in a state of dynamic equilibrium and once the balance of good versis pathogenic bacteria is compromised, it is difficult to get the gut flora back in healthy balance. Proobiotics and diet will not reestablish a healthy microbiome. One of the dominant bacterial species that resides in a healthy gut is Bacteroides genus, which does not exist in any probiotic. I have been researching "dysbiosis" for about 8 years now and have come to the conclusion that once ones gut flora has been obliterated from antibiotics, the only way to correct it is with a fecal flora implant. Hope this helps