Reversing Protein Aggregation

[shepherdgirl]

What is the role of protein aggregation in aging? What other factors are responsible for aging?
In a thread on cataracts i posted some info from Ray about lanosterol, a fungal sterol, and i will just quote it here for informational purposes:

In Ray's Sept 2015 newsletter on mushrooms, and also in an interview with Danny Roddy, Ray has mentioned that lanosterol, a fungal sterol, can reverse protein aggregation. IIUC in the newsletter he also mentions that trehalose, a fungal sugar, can stabilize cells and help prevent protein aggregation. From reading a very limited amount about making mushroom extracts, it seems to me that lanosterol would have to be extracted with alcohol, whereas trehalose would be extracted with water. (I could be wrong, i know nothing about extraction!! Could someone who knows something chime in here please??)
I have never used lanosterol or trehalose in the eyes, but i am currently putting a little trehalose in my coffee, and it tastes pretty much like sugar but less sweet. I have seen lanosterol eye drops for dogs online. Here is a segment of an herb doctor interview (on Steiner schools, actually. Could not find the date but iirc it was within the last year or so), transcript thanks to www.l-i-g-h-t.com. (I disagree with Sarah here when she mentions boiling mushrooms for lanosterol, as I mentioned above.)

ANDREW MURRAY: Well, I know we do only have a few moments left, but I do want to ask you, Dr. Peat – and, again, this is – it ties into education, it ties into research, it ties into suppression of research. And this is the latest findings of a product called lanosterol and its use in the treatment in the very real treatment of cataracts without surgery and is extremely inexpensive and it works. So what do you think about lanosterol and eye cataracts?

RAY PEAT: I was just a little surprised to see a big publication in Nature. And this group, at the University of California, San Diego, was actually reversing the majority in something like half a dozen rabbits, and then dogs. Both using eye-drops and injecting it directly into the eyeball. They actually got established cataracts to clear up. And when i wrote a newsletter about cataracts, a couple of years ago, i noticed that research in treating and curing cataracts had been suppressed because of the immense amount of money there is in removing the lens during cataract surgery; it’s a multi-million dollars business.

And that money interest had just wiped out practically all curative research in eye studies.

ANDREW MURRAY: Interesting.

So we’ll keep our eyes open for lanosterol any other future publications and, hopefully, it doesn’t get suppressed and buried in the future, so that’s something to keep an eye out for Mushrooms happen to be a good source
of that steroid.

ANDREW MURRAY: Okay. And you said it was a precursor to cholesterol.

RAY PEAT: Yeah.

It’s preceding the – the polymer that cyclizes that forms lanosterol and that turns into cholesterol.

SARAH JOHANNESSEN MURRAY: So boil your mushrooms for 45 minutes to an hour and make a yummy winter soup.

ANDREW MURRAY: And don’t think of cholesterol as a bad thing because it’s not. Okay. Well, thank you so much for your time, Dr. Peat.

So if lanosterol can reverse cataracts, what else can it do? Would it be plausible, for ex., that it could target cross-linking throughout the body or on the skin? Does anyone know of other substances that reverse protein aggregation?

 

[miki14]

Nattokinase, Serrapeptase seems to be able to dissolve misfolded proteins. Proteolytic enzymes like papaine (in papaya), bromelain (ananas), actinidin (in kiwi) break down proteins in the intestine and might also be active in the serum/plasma.

 

[shepherdgirl]

Hi @miki14 -
I agree that proteolytic enzymes can be terrific tools. As far as I know they can dissolve proteins as you mentioned. But do you know if they can actually reverse cross-linking? Un-clump a protein clump and make the protein like it was before? Or do they just dissolve clumped proteins?
Also, if they dissolve a clump of protein - for example in a cataract - would new, normal proteins then take its place, effectively restoring the tissue?
I have only heard of them unblocking arteries, removing scar tissue, etc., - which is great, because it can increase functionality - but I have not heard that they can restore tissue to an undamaged state.

 

[miki14]

Hi @miki14 -
I agree that proteolytic enzymes can be terrific tools. As far as I know they can dissolve proteins as you mentioned. But do you know if they can actually reverse cross-linking? Un-clump a protein clump and make the protein like it was before? Or do they just dissolve clumped proteins?
Also, if they dissolve a clump of protein - for example in a cataract - would new, normal proteins then take its place, effectively restoring the tissue?
I have only heard of them unblocking arteries, removing scar tissue, etc., - which is great, because it can increase functionality - but I have not heard that they can restore tissue to an undamaged state.

I'm not yet very well read about cross linking or misfolding of proteins. Activation of heat shock protein helps to clear dysfunctional, misfolded proteins. I would like to hear someones experience about natto kinase or serrapeptase.

 

[miki14]

DMSO is effective in the treatment of amyloidosis, a complication caused by misfolded proteins. Treatment of renal amyloidosis with dimethylsulphoxide (DMSO). - PubMed - NCBI

 

[shepherdgirl]

Thanks @miki14 -also check out this thread:
Aging In Human Mitochondria Fully Reversed By Glycine

 

[miki14]

Protolytic enzymes have antibiotic activity too. Antibacterial effects of natural tenderizing enzymes on different strains of Escherichia coli O157:H7 and Listeria monocytogenes on beef http://www.sciencedirect.com/science/article/pii/S0309174013006566

 

[LeeLemonoil]

According to this good looking study, both 5a-cholestan-3b-ol-6-one and 5-cholesten-3b,25-diol are much more efficient for cataracts than Lanosterol and would be easier applied. They are surely very useful in other conditions or protein aggregation /misfolding as well.

Pharmacological Chaperone for Alpha-Crystallin Partially Restores Transparency in Cataract Models


Non-Surgical Method of Treatment for Cataract - THE REGENTS OF THE UNIVERSITY OF MICHIGAN

 

[LeeLemonoil]

According to this good looking study, both 5a-cholestan-3b-ol-6-one and 5-cholesten-3b,25-diol are much more efficient for cataracts than Lanosterol and would be easier applied. They are surely very useful in other conditions or protein aggregation /misfolding as well.

Pharmacological Chaperone for Alpha-Crystallin Partially Restores Transparency in Cataract Models


Non-Surgical Method of Treatment for Cataract - THE REGENTS OF THE UNIVERSITY OF MICHIGAN

As far as I understand, these substances are human chlosterol-oxides (endigenous or synthetic?)

 

[LeeLemonoil]

Both look very much like Androgens in Structure btw, RP right again and so forth ... they are precusrsors aren't they?

The latter substance is also an important regulator in liver function and is produced in liver mitochindria:

Biosynthesis of the regulatory oxysterol, 5-cholesten-3β,25-diol 3-sulfate, in hepatocytes

 

[steel_reserve]

Doxycycline reverses prion protein infection

Doxycycline stops Prion Protein Infections - Page 3 - LymeNet Europe

 

[shepherdgirl]

@LeeLemonoil - you are saying that 5a-cholestan-3b-ol-6-one and 5-cholesten-3b,25-diol are androgen precursors? Are these substances that only the pharmaceutical industry would be able to isolate or synthesize, or do you think they would be readily available to the public?
Thanks for posting these studies!!

 

[Drareg]

Methylene blue helped with Alzheimer's protein aggregation.

 

[2thecloudsabove]

Lanosterol is precursor for 7-Dehydrocholesterol. Is there any rich food os supplement of lanosterol?

 

[LeeLemonoil]

@LeeLemonoil - you are saying that 5a-cholestan-3b-ol-6-one and 5-cholesten-3b,25-diol are androgen precursors? Are these substances that only the pharmaceutical industry would be able to isolate or synthesize, or do you think they would be readily available to the public?
Thanks for posting these studies!!

@shepherdgirl

Yes, they sure look like Androgens structure-wise and cholesterol is the main substrate for steroid synthesis in the body.
Both sbstances are available via biochem suppliers like steraloids and Sigma-Aldrich, though I don't know how difficult /expensive production is and if they are isolated or synthesized.

@haidut might have additional knowledge about it

 

[shepherdgirl]

Is there any rich food os supplement of lanosterol?

Yes, mushrooms as mentioned above- but possibly the lanosterol would need to be extracted with alcohol. Also i seem to remember @haidut mentioning that there could be traces of lanosterol in his tocovit, but i don't know how much. As for other food or supplement sources, other than the lanosterol drops for pets - no idea.

Methylene blue helped with Alzheimer's protein aggregation.

Thanks Drareg - wondering if you have any relevant research on this? Did it actually reverse aggregation or did it clear it out?

Wondering if it wd be possible for the body to utilize its own lanosterol and androgen precursors for this kind of healing - has anyone heard of cataracts or protein tangles reversing for example? In 'aging' is there a natural tendency toward aggregation that the body is continually resisting, but that the people without enough precursors to steroid hormones eventually succumb to? And can increasing the rate at which the body produces these substances slow down or reverse aggregation?
A 10 second internet search seemed to indicate that low cholesterol and/or statins are associated with higher risks of Parkinson's and cataracts for ex. (But those are just brief health articles and nothing i would rely on. For example one cataract article mentioned statins increasing cataract risk and then went on to blame high cholesterol!)

 

[Drareg]

Yes, mushrooms as mentioned above- but possibly the lanosterol would need to be extracted with alcohol. Also i seem to remember @haidut mentioning that there could be traces of lanosterol in his tocovit, but i don't know how much. As for other food or supplement sources, other than the lanosterol drops for pets - no idea.

Thanks Drareg - wondering if you have any relevant research on this? Did it actually reverse aggregation or did it clear it out?

Wondering if it wd be possible for the body to utilize its own lanosterol and androgen precursors for this kind of healing - has anyone heard of cataracts or protein tangles reversing for example? In 'aging' is there a natural tendency toward aggregation that the body is continually resisting, but that the people without enough precursors to steroid hormones eventually succumb to? And can increasing the rate at which the body produces these substances slow down or reverse aggregation?
A 10 second internet search seemed to indicate that low cholesterol and/or statins are associated with higher risks of Parkinson's and cataracts for ex. (But those are just brief health articles and nothing i would rely on. For example one cataract article mentioned statins increasing cataract risk and then went on to blame high cholesterol!)

Methylene blue does not reverse existing neurofibrillary tangle pathology in the rTg4510 mouse model of tauopathy
This study mentions the in vitro results,it's good to keep healthy scepticism about anything as cheap and relatively natural as methylene blue when viewing studies,pick through them.

Skip to part 9 in the study below.
http://www.mpasmb-hamburg.mpg.de/mand-pdf/Schirmer__Mandelkow_2011_NeurobiolAging_MethyleneBlue.pdf

 

[LeeLemonoil]

Curcumin, Myricitin and Thioflavin T are also powerful at inhibiting and probably reversing some forms of PA.

 

[aarfai]

Has anyone tried lanosterol? It seems to be a Peat molecule as I understand it

 

[shepherdgirl]

@Drareg - belated thanks for posting these MB studies!
@aarfai - i never used lanosterol. The reviews on lanosterol for dog cataracts that i read on amazon were mixed.