Time to reject the hypothesis that alpha-synuclein aggregation is toxic

[Farooqji]

ncbi.nlm.nih.gov/pmc/articl...

[wriga]

15 years wasted looking for a toxic component in misfolded a-synuclein.

[Parkinsonjisung in reply to wriga]

there's a good thread on it here:

twitter.com/AlbertoEspay/st...

I think most of the experts agree that it was doomed to failure from the start but not cause the hypothesis is wrong. It maybe wrong, but it seems this trial didn't prove much either way

[park_bear in reply to Parkinsonjisung]

In order to limit the large amount of literature they had to review, the above-cited study excluded animal models. Understandable. Unfortunately, as a result, that excluded a key finding –a genetically modified mouse that forms defective alpha synuclein and as a result suffers from PD. The model makes an appearance in this study: Reduction of Lewy Body Pathology by Oral Cinnamon

link.springer.com/article/1...

" Upon oral administration, cinnamon markedly reduced the level of insoluble α-syn in nigra, hippocampus and brain stem of A53T mice... both cinnamon and NaB treatments showed improvement in their motor and cognitive functions."

I personally confirmed that taking cinnamon does significantly improve Parkinson's. I will be writing further about this in due course.

This is strong evidence that defective alpha synuclein does cause Parkinson's. The title to the above post is wrong.

[jimcaster in reply to park_bear]

But, Park Bear, don't you think part of the problem is that the mice don't actually have Parkinson’s Disease. Whether they are genetically or chemically modified to have Parkinson’s symptoms, they don't actually have PD and they obviously aren't humans. I'm tired of reading about success in mice and failures targeting alpha synuclein in humans.

[park_bear in reply to jimcaster]

There has been no failure of human treatment in this case that I am aware of, and one success. Nothing to be tired of here.

[redhawk1 in reply to park_bear]

Besides being able to correctly identify the misfolded protein in the PD brain the medication (or body) must also be able to dispose of all that crummy protein. Only a guess but I think Biogen sees that as well!

[Despe in reply to jimcaster]

I'm tired of reading about success in mice and failures targeting alpha synuclein in humans.

Me, too, Jim.

Having said that, I love cinnamon to the point I am scared I have damaged my liver although I use Ceylon, Organic. I convinced my husband that it is good for his PD, and then some, so he takes about 1/2 tsp in his keto breakfast. Don't know if that is sufficient quantity to "reduce" α-syn.

[park_bear in reply to Despe]

I have checked the literature with regard to Ceylon cinnamon safety. I did not find any indication of adverse effects even at high doses. One study had patients taking 6 g of cinnamon daily and not reporting any adverse effects. So no worries about liver damage as far as I am able to tell.

[Despe in reply to park_bear]

Thanks, PB. I love and have used it since I was a young lady. So, the "therapeutic" dose is 6 g a day?

[park_bear in reply to Despe]

I had an adverse reaction at this 6 g per day dosage. I would put the therapeutic range at somewhere between .5 and 3 g per day. I would suggest mixing it with food or drink.

[Despe in reply to park_bear]

Thanks! I will convert that (.5 - 3 g) to measuring spoon.

[gwendolinej in reply to park_bear]

I’m glad we have members like you (and others) to interpret these articles for plebes (plebs) like me.

I look forward to your post on cinnamon.

Gwendoline

[Despe in reply to park_bear]

PB,

Looking so much forward to your post on Cinnamon.

[MarionP in reply to Parkinsonjisung]

"most of the experts agree"

It's been a long time looking into and not necessarily a dead end, it's not true at all that "most of the experts agree."

Also there are mechanism issues that have nothing to do with this hypothesis, but with maybe a new hypothesis I think you are proposing: testing through actual clearing of some kind, technically termed "reversal"... not much of which has yet to even be accomplished (assuming it someday can be...but whether it can, or can't, is also speculation...).

Cause and treatment are entirely different scientific enterprise questions, research, and experimentation questions. The former is what the last decade of work has been about, nearly nothing about the latter...because it can't/hasn't been be accomplished yet.

All that's really been proved is that however it was made or arrived, the garbage is in the building but the waste removal system can't collect or get it out to the curb. That's all. It's only one idea strand that says then that what happens to a building that can't get the trash out to the curb is destroyed by that garbage. That's definitely possible, but even that isn't established as the cause of the disease. Maybe all the tenants got tired of the smell and left, and that's the link that kept the garbage from getting outside. But what made them leave, the garbage, or something else (the view, the water, the crime rate, the rent)? We don't know. And if we don't know, then we also don't not know. You want to quote science, you have embrace all of it.

For instance, what is toxic about perhaps a waste removal system that can't remove this garbage before it clumps, or some enzyme being able to slice it up into more manageable parts or disaggregate the proteins by targeting the misfold as a marker and then dissolving parts of the proteins like a clot buster does, then those parts or components thus catabolized become within the waste removal system to remove...assuming that the process of accumulating or aggregating those clumps in the first place wasn't toxic itself enough to damage the machinery too far in the first place? All are open questions, not resolved ones. And that's for starters.

Now the cinnamon thing is really interesting.

[rescuema in reply to MarionP]

"All that's really been proved is that however it was made or arrived, the garbage is in the building but the waste removal system can't collect or get it out to the curb."

Exactly.

[Parkinsonjisung in reply to MarionP]

I was simply referring to the experts in that twitter thread who agreed that the drug used in the trial was doomed to fail, not the alpha syncleuin clumping theory

[MarionP in reply to Parkinsonjisung]

Ok, very good.

As Emily Litella used to say, "Never mind."

[Hidden in reply to MarionP]

Hi MarionP - what was said about cinnamon?

[MarionP in reply to Hidden]

Just above, talk to park_bear...we're all wanting to hear more on what he's experiencing...as he gains it. And he's systematic enough to know to try one thing at a time, which is good, unless some hidden additive effect is afoot...or a leg.

Either way it's going to be encouraging I suspect.

[Getz]

Chartist can you please explain in basic English what this is o about?