There is a strong connection between amyloids in general and the innate immune response, inflammation, and oxidative stress.

For example,

Triggering of Inflammasome by Aggregated α–Synuclein, an Inflammatory Response in Synucleinopathies

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0055375

Recognition of the generic amyloid structure by the innate immune system may have evolved as a way of recognizing the bacterial amyloid that makes up bacterial biofilms

http://www.ucdmc.ucdavis.edu/welcome/features/20090909_Alzheimers/

Responses to amyloids of microbial and host origin are mediated through Toll-like receptor 2

http://www.sciencedirect.com/science/article/pii/S1931312809002133

Note: I'm not saying that alpha-synuclein is the only source of inflammation in Parkinson's, just that these factors are interconnected to a high degree that makes it difficult to distinguish upstream and downstream causes and effects.

Thanks Jeff, I rely on you these days. I am still surprised at how much anti-inflammatories improve PD symptoms. Of course you can't prescribe prednisolone at 20-30 mg/day without a lot of side effects but budesonide is tailored not to have so many. It is also encapsulated for release in the colon, where it acts directly to alleviate colitis. It is then broken down in the liver so that little is supposed to be released into the bloodstream, minimising side effects. I'm therefore surprised that it is so effective against joint inflammation ...... but then is there a connection with α-synuclein being found in the colon of PD patients - maybe before any symptoms appear?

Jeff or Stefan, do you know if amyloid formation is a problem in PD. I just know about AD and beta amyloid formation. Does this also occur in PD? the reason I ask is that I study AD as it relates to alpha, beta and gamma secretases.

If the amyloids form in PD, maybe the inflammatory component is related to the action of the proteinases that process the amyloid. For example, ADAM17 could be an alpha secretase activated by inflammatory molecules, etc. I am not sure about what activates BACE. Also, does the amyloid formation promote inflammation, and/or does the inflammation promote the amyloid formation.

Direct link between an alpha-synuclein fiber injection, Lewy pathology, and loss of dopamine neurons in anatomically connected regions

Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice

http://www.sciencemag.org/content/338/6109/949

As far as I know amyloid formation promotes inflammation, although the possibility of positive feedback exists. For example with AD Abeta can lead to inflammation, BACE activation, more amyloid etc. :

BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and β-amyloid production in Alzheimer’s disease

http://www.molecularneurodegeneration.com/content/7/1/52

with Parkinson's a similar mechanism may exist as outlined in the article attached

I was interested to read that not only is α-synuclein found in colon of PwP but so are Lewy Bodies (http://www.ncbi.nlm.nih.gov/pubmed/23017648).   It also seems that diarrhoea is often associated with PD (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012728#s1).  In an RG thread on Serotonin and Dopamine William Wilson introduced me to the role of enzyme co-factors, which links serotonin synthesis to dopamine (see file).  (William warned me that one of the authors had been struck off for self medication and that urinary levels of neurotransmitters are not a reliable indicator of CSF levels but this does not invalidate the interconnectedness of the cofactors.)  It is this that offers potentially a way to understand why PD has so many manifestations.  It still leaves us (me, anyway) unsure as to whether misfolded α-synuclein is a cause or a symptom of PD and, if it is a cause, then its role in the process.

 Inflammation causes lipid peroxidation.

Lipid peroxides spontaneously degrade via Hock cleavage, forming aldehydes.

Aldehydes cause protein cross-linking, protein misfolding, and aggregation.

Protein aggregates accumulate and cause inflammation, forming a positive feedback loop and disease progression.

The same thing happens in Lewy body disease and in Alzheimer's disease.

Aldehyde scavengers have been shown to prevent protein aggregation in vitro for both disease models.

Good papers on this are:

http://www.ncbi.nlm.nih.gov/pubmed/?term=15794636

http://www.ncbi.nlm.nih.gov/pubmed/?term=19841277

More information (including dietary treatment options) is available at:

http://www.google.com/patents/US20130165515

 Dietary supplements that I recommend for treating neuroinflammation  include:

Glutamine powder, 5g/day (one teaspoon)

Amazingly anti-inflammatory, see:

http://www.ncbi.nlm.nih.gov/pubmed/?term=7257951

Glutamine also up-regulates glutathione.

N-acetylcysteine, ~1g/day

A prodrug for cysteine and acetyl groups. Increases glutathione, the most important cellular anti-oxidant and detoxifier.

Acetyl N-carnitine, ~1g/day

Improves cellular energetics by providing a shuttle for fatty acids between mitochondria and peroxisomes, promotes neuronal growth, and is a prodrug for acetyl groups.

Increasing acetyl groups can increase protein acetylation (including histone acetylation, which has multiple anti-aging and anti-inflammatory effects).

Another dietary supplement that I recommend (Allium-Z, 2 capsules/day) scavenges aldehydes, and is therefore specifically neuroprotective (rather than the other supplements, which are primarily anti-inflammatory). It is available for experimental and compassionate use in the USA (and is available commercially in the EU). You can contact me for details.

All of these dietary supplements are generally beneficial, and have minimal (or no) non-beneficial side effects. You can take them along with your other meds. Let me know the results.