Proteins central to the pathology of Alzheimer’s disease act as prions

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#91

Post by dekhn » Thu, May 02, 2019, 3:31 PM UTC

fjfaase wrote: post #76

netwanderer3 wrote: post #65

Earlier quoted context omitted.

You're right, I used to know a few vegetarians who often supplement their diets with Vitamin B-12 which theoretically could help boosting and balance their cognitive ability vs. meat eaters. I personally did not notice any cognitive problems in those people at least. Our DNA contains the sequence of folding steps instruction for each protein to fold. So for a protein to misfold itself, could this mean it must have re…

As I understand it, the DNA only contains the sequence of amino-acids from which the protein is built, not their folding instructions. Some proteins are also modified and/or cut in pieces by other proteins before reaching a functional state. Discovering how a protein folds, is a very complex problem, that would have been much easier if it were indeed encoded by the DNA. the website https://fold.it/portal/ gives a goo…

For many proteins, the sequence encodes the fold (many small proteins refold spontaneously with just their amino acid sequence). That proteases or other activations may be required to functionalize the protein is irrelevant- the sequence in the DNA causes the protein to fold to its preprotein state reversibly.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#92

Post by dekhn » Thu, May 02, 2019, 3:32 PM UTC

cjbprime wrote: post #90

dekhn wrote: post #84

Earlier quoted context omitted.

senior author of the article was the person who established that prions are a legitimate disease caused by protein folding he had to fight an uphill battle for over 20 years to get his ideas established so I'm going to actually give him a ton of credit and the ability to publish what he wants to because he's already demonstrated he's responsible. He also won the Nobel prize for that work.

You could modify your belief in his authority based on the fact that this result was presumably rejected by top-tier journals, and probably for non-trivial reasons. I don't know anything about the field so I can't say whether that's appropriate here. But if you're willing to grant credence based on a prior Nobel, you should be willing to consider taking some away based on the publishing journal's reputation. Why woul…

Where did you get the idea his work was rejected? Also, his work was rejected by top journals for decades until people finally realized he was correct.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#93

Post by dekhn » Thu, May 02, 2019, 3:34 PM UTC

8note wrote: post #48

autokad wrote: post #39

Earlier quoted context omitted.

one of the authors discovered prions, so I am not so quick to discount their work.

that's an argument from authority rather than one of science though. we believe things only once we've exhausted our attempts to disprove it

Prusiner actually proved his case well over a decade before the establishment was ready to accept his findings. They literally denied his results were true and accurate. Accepting that proteins can catalyze misfolding in a cascade was not an easy thing for the establishment to accept (however, by the time I attended UCSF, prusiner's work was already being suggested to be valid, and people were already working on mechanism).

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#94

Post by dnautics » Thu, May 02, 2019, 3:39 PM UTC

Marsymars wrote: post #46

traek wrote: post #42

Earlier quoted context omitted.

Sure, but this particular study came out of the lab of the Nobel-prize-winning scientist who literally discovered prions. I think it's at least worthy of discussion.

Prusiner has been on the path to this study for quite a while, at least since a talk of his I attended in 2011.

He was on that path in 1999 when I skipped a day of high school to attend a lecture he gave. (I also later became a prion researcher, specifically in a lab that worked with Alzheimer's).

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#95

Post by jessriedel » Thu, May 02, 2019, 3:47 PM UTC

dekhn wrote: post #92

cjbprime wrote: post #90

Earlier quoted context omitted.

You could modify your belief in his authority based on the fact that this result was presumably rejected by top-tier journals, and probably for non-trivial reasons. I don't know anything about the field so I can't say whether that's appropriate here. But if you're willing to grant credence based on a prior Nobel, you should be willing to consider taking some away based on the publishing journal's reputation. Why woul…

Where did you get the idea his work was rejected? Also, his work was rejected by top journals for decades until people finally realized he was correct.

If it could have been published in Science, then it wouldn't have been submitted to Science Translational Medicine, a completely different journal with much less visibility (and a much lower impact factor). For some of these Nobel guys you could argue they want to avoid supporting the flashy magazines and don't care about getting into the high impact journals because they are already established, but in this case he actually submitted to a Science-family journal, so he's very unlikely to be making some principled stand.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#96

Post by jessriedel » Thu, May 02, 2019, 3:49 PM UTC

autokad wrote: post #39

cjbprime wrote: post #14

Y'all, please never post university press releases about single scientific studies . They are the worst thing. Every major human problem has been declared solved by one of them. They are even worse than posting single scientific study papers themselves at the time of publication, and that's still pretty bad, because of the overwhelming incentive to create exciting studies that are wrong, and our current inability to…

one of the authors discovered prions, so I am not so quick to discount their work.

If the author discovered prions, wouldn't this make him strongly biased toward thinking that prions are the key to solving important problems?

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#97

Post by dekhn » Thu, May 02, 2019, 4:22 PM UTC

jessriedel wrote: post #95

dekhn wrote: post #92

Earlier quoted context omitted.

Where did you get the idea his work was rejected? Also, his work was rejected by top journals for decades until people finally realized he was correct.

If it could have been published in Science , then it wouldn't have been submitted to Science Translational Medicine , a completely different journal with much less visibility (and a much lower impact factor). For some of these Nobel guys you could argue they want to avoid supporting the flashy magazines and don't care about getting into the high impact journals because they are already established, but in this case h…

You claim is entirely speculative. There may be good reasons why it didn't show in Science (page space is extremely limited)

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#98

Post by cjbprime » Thu, May 02, 2019, 5:29 PM UTC

dekhn wrote: post #97

jessriedel wrote: post #95

Earlier quoted context omitted.

If it could have been published in Science , then it wouldn't have been submitted to Science Translational Medicine , a completely different journal with much less visibility (and a much lower impact factor). For some of these Nobel guys you could argue they want to avoid supporting the flashy magazines and don't care about getting into the high impact journals because they are already established, but in this case h…

You claim is entirely speculative. There may be good reasons why it didn't show in Science (page space is extremely limited)

Yes, it's speculative. But so is the idea that this work is correct because he won a Nobel in the past. That's the point: you're making guesses based on limited evidence, and we're pointing out that you didn't use all available limited evidence to influence your guess, just some evidence that confirmed what you already felt. This is a kind of bias.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#99

Post by cjbprime » Thu, May 02, 2019, 5:45 PM UTC

rossenberg79 wrote: post #74

cjbprime wrote: post #14

Y'all, please never post university press releases about single scientific studies . They are the worst thing. Every major human problem has been declared solved by one of them. They are even worse than posting single scientific study papers themselves at the time of publication, and that's still pretty bad, because of the overwhelming incentive to create exciting studies that are wrong, and our current inability to…

The worst part is that while articles about a disease like this are a mere annoyance to us, for people with loved ones with the disease or suffering from the disease itself it becomes a cruel joke. These are people who scour the internet looking for any information they can find and carefully read articles like this looking for a bit of hope that there may be a solution. But it’s bullshit. Don’t share these articles,…

Totally agree.

Re: Proteins central to the pathology of Alzheimer’s disease act as prions – study

#100

Post by jeffdavis » Thu, May 02, 2019, 6:33 PM UTC

robbiep wrote: post #40

jeffdavis wrote: post #16

How does a protein come to be misfolded? Is it a random mutation that happens to be self-propagating? Is it different between alzheimers and other ones like mad cow?

Thermodynamics. Certain proteins have a propensity to Misfold, this is driven by the folding conformations as well as by Heat Shock Proteins. The underlying genetics that drive amino acid sequence are the basis for this. In the best known prion disease, Mad Cow, one misfolded protein drives other similar proteins it runs into to induce the same conformation. Due to the thermodynamics of folding, it is now in a very s…

So the first misfolded protein is just a random occurrence?

With mad cow, will uninfected cow populations spontaneously develop mad cow on their own? Or was the first mad cow protein a rare misfortune not likely to happen again? Or did the first mad cow protein come from something other than a cow?