New Hope for Diseases of Protein Folding Such as Alzheimer’s, Parkinson’s Diseases, ALS, Cancer and Diabetes

In this study a complete screening of all 19,000 genes from the transparent roundworm was done.
In the work, they looked to see, one gene at a time, whether the gene suppressed protein aggregation in the cell. Did the gene increase aggregation or lessen it or have no effect at all?

The researchers found 150 genes that did have an effect. They then conducted a series of tests and zeroed in on nine genes that made all proteins in the cell healthier. (These genes had a positive effect on a number of different proteins associated with different diseases.)

These nine genes define a core homeostastis network that protects the animal's proteome (the entire set of proteins expressed by the organism) from protein damage. Nine are also a much more manageable number to study.

In another study done by the same lead researcher, Morimoto and his colleagues screened nearly one million small molecules in human tissue culture cells to identify those that restore the cell's ability to protect itself from protein damage.

They identified seven classes of compounds (based on chemical structure) that all enhance the cell's ability to make more protective molecular chaperones, which restore proper protein folding. The researchers call these compounds proteostasis regulators. They found that the compounds restored the health of the cell and resulted in reduction of protein aggregation and protection against misfolding. Consequently, health was restored when diseased animals were treated with the small molecules.

Morimoto and his team then conducted detailed molecular analyses of 30 promising small molecules, representing all seven classes. They discovered some compounds were much more effective than others.

Dr. Barry Sears of Zone diet fame, in his book The Omega Rx Zone, says high dose fish oil, at least 10 g per day, is beneficial in PD. He cites anecdotes of reversing symptoms with 25 g.

Fish oil addresses the misfolded protein problem.

http://psychcentral.com/news/2009/04...sons/5424.html

I wonder what other substances also do so.

I had a patient before I retired who had autoimmune kidney disease. He was taking 15 grams of fish oil, on the advice of his kidney doctor, who found a paper from China showing it can reverse some autoimmune organ damage. And it worked for him.

It worked for him! We used to have interesting conversations...and I ultimately suggested he try gluten free and he did and reversed his GI issues!( he used 300mg of Zantac a day for YEARS!) The gluten intolerance could have been his trigger.

I googled proteostasis regulators and came up with a number of interesting articles. I even found one that discussed a substance that seemed to help out with those misfolded proteins in the specific mutation that I have and believe is the cause of my PD (the N370S carrier of Gaucher disease which increases risk of PD). The substance is Celastrol. Anyone know anything about this?

I am awed and inspired by the brainpower I have found here!

Best,
wordsmithy

Hi wordsmithy,
How do they find the right molecule for each gene? will tbe process be in clinical trials any time soon? know anything about delivery?

it sounds promising if it's easily delivered and the correct molecule is easily found.

isn't this really about electrical charges that stop from the folded proteins?

adding just reread victoria's post . it's a big jump from a worm to a person.

Yes, we are talking mice, earthworms, and petri dishes. But this substance is available as a chinese herbal compound called Thunder of God vine. Seems to have anti-tumor, immuno-suppressant properties, used for cancer, rheumatoid arthritis. Under investigation for PD and Alzheimer's.

I wouldn't take it unless under the care of a TCM doctor.

Relevant articles I found:

Cell, 2008: Proteostatis Regulators and Pharmocologic Chaperones Synergize to Correct Protein Misfolding Diseases.

Journal of Neuroinflammation, 2010: Reduction of β-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer's disease

Best,
wordsmithy

http://the-scientist.com/2012/01/01/...-chronic-pain/