Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
(find topics using search [upper left] or index [lower right]), and
more articles by Prof. Ayers on Suite101 .

Wednesday, December 24, 2008

Synuclein and Amyloid Diseases

NSAIDs, such as ibuprofen and aspirin are possible treatments to inhibit the aggregation of proteins (synuclein, beta amyloid) on charged polymers in amyloid diseases, such as Parkinson’s disease, Alzheimer’s disease, etc. Contradictory studies show that intracellular aggregate formation may be protective, since dimers are more toxic than aggregates.

The list of amyloid diseases is long and there are few effective treatments. In each case a protein starts to accumulate in fibers that form amyloid plaques inside or outside the cells. The large aggregates outside are toxic. Inside it appears that the large aggregates are not as toxic as small clumps, oligomers, of the protein.

The amyloid proteins are stacked up in the fibers in a very organized way, so that the same portions of the protein are lined up on each side of the fibers. Outside the cell, the regions with basic amino acids interact with heparin, and in Alzheimer’s disease, for example, the beta amyloid plaque is half heparin. In test tube experiments, fiber formation from protein solutions is accelerated by adding heparin.

Amyloid fibers also form inside cells in the case of the tau fibers of Alzheimer’s disease or the synuclein aggregates in Parkinson’s disease. In theses cases, there should not be any intracellular heparin, and it is not known what polyanion (RNA?) serves to accelerate fiber formation in these cases.

Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and aspirin, reduce the incidence of Parkinson’s and Alzheimer’s diseases. It has recently been shown that in test tube experiments, NSAIDs also decrease the formation of amyloid fibers from synuclein.

Amyloid fibers can be stained by Congo Red and thioflavin. Curcumin is the active component of tumeric and it has a structure related to Congo Red. Curcumin has been shown in recent studies to block synuclein amyloid formation.

In addition, the heparin in the fiber complexes can be stained with berberine. Berberine is a traditional herbal treatment for arthritis. It would not be surprising if it was also effective against Alzheimer’s amyloid plaque.

The large extracellular plaque aggregates appear to be toxic, but the small, oligomeric aggregate of protein appear to be the toxic form in cells. Recent experiments show that facilitating the formation of large intracellular aggregates minimizes the toxicity in animal models of Huntington’s and Parkinson’s diseases. It appears that the large visible aggregates are not the form that kills the cell.

For the time being, the only safe treatments that focus on amyloid fiber formation are the NSAIDs, curcumin and perhaps berberine.

references:
Hirohata M, Ono K, Morinaga A, Yamada M. 2008. Non-steroidal anti-inflammatory drugs have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro. Neuropharmacology 54(3):620-7.

Pandey N, Strider J, Nolan WC, Yan SX, Galvin JE. 2008. Curcumin inhibits aggregation of alpha-synuclein. Acta Neuropathol. 115(4):479-89.

Bodner RA, Outeiro TF, Altmann S, Maxwell MM, Cho SH, Hyman BT, McLean PJ, Young AB, Housman DE, Kazantsev AG. 2006. Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington's and Parkinson's diseases. Proc Natl Acad Sci U S A. 103(11):4246-51.

Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, Young AB, Abagyan R, Feany MB, Hyman BT, Kazantsev AG. 2007. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science. 317(5837):516-9.

5 comments:

Nigeepoo said...

Hi. As you know, this subject is very relevant to me due to my mum's Lewy Body Dementia. I have ordered Goldenseal & Turmeric extracts, to see if they can improve my mum's condition. As my mum doesn't like taking pills, I shall try dissolving them in water and add the solution to her cartons of fruit juices in the fridge (unless it tastes horrible).

I'm not keen on giving my mum Aspirin as she suffers from acid reflux due to hiatus hernia and is on 20mg/day Omeprazole and occasionally uses Gaviscon.

She and I have noticed a recent reduction in her Parkinson's tremor as well as slightly improved mental function. This may or may not be due to her increased intake of smoked salmon. I will wait a few more weeks before starting her on Goldenseal etc as I don't want to make too many changes at the same time.

Many thanks for your blog posts, which I always find most interesting. Cheers, Nige.

Tanya said...

Source(s):

John C.S. Breitner, MD, MPH, of the VA Puget Sound Healthcare System and head of geriatric psychiatry at University of Washington School of Medicine.

"The reason why most people in this age group take NSAID drugs is not for Alzheimer’s prevention, but to quell the discomfort of arthritis -- a fact that raises the obvious question of whether something about arthritis might relate to the development of AD. Dr. Breitner says that his study and others have looked at that, and the answer seems to be no -- it is apparently attributable to the drugs not the disease."

The above is taken from an article about the referenced study. The rest of the article is here http://view.ed4.net/v/PP0ASM/08KBA/IYVN2TI/26N0S7/MAILACTION=1&FORMAT=T

Wondering if Dr Ayers would have a different take on the results...

Dr. Art Ayers said...

Tanya,
Of course I have a different view.
It is strange to me, but typical of the medical researchers, that they don't try to explain what is causing arthritis, Alzheimer's or NSAID damage. The quick answers are chronic inflammation (BBB damage) and leaky gut.

Chronic inflammation is behind the arthritis, and it it was treated by reduction of the contribution of inflammatory components in the diet, instead of NSAIDs, then the risk of Alzheimer's would be reduced. Most people would rather believe that arthritis and Alzheimer's is an inevitable result of genetics and aging, than just change their diet and lifestyle to avoid the consequences of chronic inflammation.

Thanks for your comments.

Tanya said...

Since I am still dealing with aches and pains despite the diet shift and Vit D & C...what about Tylenol? How does it work and is it a better alternative than NSAIDS?

Dr. Art Ayers said...

Tanya,
If you have already exploited fish oil and vitD, then it is good to alleviate the pain with Tylenol rather than the COX inhibitors that alter gut development and lead to leaky gut, etc. The tylenol won't help with inflammation that may be causing the pain, but less pain may permit more mobility, which will help.

Thanks for providing updates.