
Parkinsons-Like Neurodegenerative Disease Linked to Prion - cryoshon
http://cen.acs.org/articles/93/i35/Another-Neurodegenerative-Disease-Linked-Prion.html
======
melling
I gave to the Michael J Fox foundation last year so I'm on their mailing list.

[https://www.michaeljfox.org/](https://www.michaeljfox.org/)

There seems to be a lot of research and progress into the disease. Andy Grove
of Intel has been fighting the disease.

[http://www.forbes.com/forbes/2008/0128/070.html](http://www.forbes.com/forbes/2008/0128/070.html)

We've been fighting diseases like these for a while. It would be nice to get a
few more wins.

------
narrator
There is no conventional treatment for prion disease, but methylene blue
(Methylthioninium chloride), which has been around for over 100 years, has
been investigated as a _preventive_ treatment with some success in mouse
models:

[http://www.ncbi.nlm.nih.gov/pubmed/23022479](http://www.ncbi.nlm.nih.gov/pubmed/23022479)

[http://www.ncbi.nlm.nih.gov/pubmed/25958115](http://www.ncbi.nlm.nih.gov/pubmed/25958115)

The problem is is that it's not patentable and it's super cheap. Thus, various
drug companies like TauRX are tweaking it a little so it's patentable and are
currently trying to get it through clinical trials.

[http://taurx.com/science](http://taurx.com/science)

~~~
DiabloD3
What's really interesting is the nootropic crowd has been experimenting with
methylene blue for years; a lot of stacks published by nootropic enthusiasts
have featured it to increase ATP production (same reason why I take
methylcobalamin for my B12).

I personally suspect a lot of "modern" neurodegeneration diseases (such as
Alzheimer's) are directly linked to malfunction and eventual death of
mitochondria through years of abuse by poor dietary standards, especially in
the US, as in, not enough of the B vitamins (which participates in the
production of ATP, CoA, acetyl-CoA, NAD, NADP, etc), including Choline and
PABA (not usually considered B Vitamins, but have, at one point, been assigned
B numbers).

~~~
caycep
maybe, but the BS detector of a lot of people in the field are ticked off when
someone tries to propose one cause for a broad variety of biologically
different disease. It's also hard to prove that it isn't a general effect, vs
the cause, of badness. mitochondrially-powered eukaryotic cells are awfully
more susceptible to many things and my cynicism suspects you can measure
worn/beaten up mitochondria in pretty much anyone as they age. The last CoQ10
trial that was based on the mitochondrial stuff for Parkinson's failed
miserably.

If someone can design an experiment to prove a causative role of mitochondria
in all of this, more power to them, but a lot of the proposed mechanisms never
really appealed to me as all that compelling, other than to note correlation,
i.e. "All of our Disease X patients exhibits abnormal test Y, which could
potentially, possibly, but not definitely, be related to mitochondrial
dysfunction, and this is why the NIH should give our group more grant money
next year!"

~~~
DiabloD3
I don't understand the point of supplementing CoQ10 alone. CoQ10 is one of
about twenty or thirty things that should be supplemented if, indeed, this is
the correct route to improving life.

~~~
caycep
IMHO, it was the easy way out. You do a trial with one substance at a time,
and do a simple randomized controlled trial; which is how most of medical
research works. More than one agent and you have to hire more statisticians to
do your experimental design, and it is harder to get somewhat simpleminded
grant committees to understand your proposal.

------
josu
I found prions to be the most fascinating thing in my biology classes. And the
fact that we still don't know that much about them bemuses me. The debate
section from the Wikipedia is worth reading [0] due to the fact that we still
don't know "Whether prions cause disease or are merely a symptom caused by a
different agent is still debated by a minority of researchers".

[0]
[https://en.wikipedia.org/wiki/Prion#Debate](https://en.wikipedia.org/wiki/Prion#Debate)

~~~
dekhn
I think that debate is mostly being waged by people who don't want to accept
that our existing models of disease are woefully simplistic. I find it mainly
amusing because the previous battle similar to this was from people who
thought nucleic acids couldn't be coding molecules while proteins could!

I was at UCSF when Prusiner was doing some of his best work on prions- it
typically involved infecting mice and waiting 2 months to get a result that
could be analyzed molecularly.

Anyway, this model system:
[https://en.wikipedia.org/wiki/Fungal_prion](https://en.wikipedia.org/wiki/Fungal_prion)
is pretty well understood, and it's generally hoped that understanding its
molecular behavior will go a long way to understanding mammalian prions.

~~~
mohawk
> I find it mainly amusing because the previous battle similar to this was
> from people who thought nucleic acids couldn't be coding molecules while
> proteins could!

Did you mean s/be coding molecules/have catalytic function/ ?

~~~
dekhn
No, although that was another interesting battle.

I'm referring to the determination that DNA, not protein, was the hereditary
molecule. I probably just worded this poorly, to give the implication that
coding capability was limited to proteins. It's just that most people at the
time thought that DNA was found in either nA (a string of As), nT, nG, or nC,
or random arrangements. More than anything people just didn't think that DNA
could "code" for anything, while proteins could, because people didn't seem to
realize that unique sequences of heteropolymers was a valid form of coding. It
was mostly thought that the information was stored in huge structures formed
by proteins, and that the coding information was architectural.

See Mayr, "Origin of Biological Thought", final chapter, starting with the
section on Meischer. Or Crick's "On Protein Synthesis" where he proposed the
linear code:
[http://profiles.nlm.nih.gov/ps/access/scbbzy.pdf](http://profiles.nlm.nih.gov/ps/access/scbbzy.pdf)

------
pasbesoin
I'm reminded being scoffed at: "It's not contagious."

I don't mean to be part of a panic, but there's been a lot of "it isn't" based
not on science but on, frankly, opinion.

Nowadays they think that they can link something like 25 - 30 % of cancers to
viral infections. (I seem to recall 25 being more current, with 30 being
expected soon.)

In a broader context, sooner or later we will have to re-evaluate things like
OCD. (I'm thinking of the hand washing and "cleanliness" aspects, currently.)
They may not be "merely" a disease or disfunction, but rather an extremity on
yet another "spectrum", one that may in some circumstances actually provide an
advantage. Perhaps explaining its continued occurrence.

Prions are new to our understanding. Except, as we continue to look at long-
standing human behaviors, now with knowledge of them, we may find that,
indirectly, they are not entirely new to our understanding and behaviors.

(Nonetheless, I agree with others here and in general: Scary stuff.)

P.S. I wonder whether/when we will discover any advantageous aspects to some
of them, or at least benign.

~~~
srj
While the cause remains unknown there's research showing that OCD may in part
be triggered by infection:
[http://www.nimh.nih.gov/health/publications/pandas/index.sht...](http://www.nimh.nih.gov/health/publications/pandas/index.shtml)

------
hammock
Prions are scary, for the reason that "all known prion diseases...are
untreatable and fatal." How do you stop a prion? For that matter, how do you
stop anything in the brain (without cutting it out)?

~~~
chokma
Prions are indeed scary - I still remember a comment to the effect that
pathologists can never be really sure their instruments are safe to work with
again.

(
[http://pipeline.corante.com/archives/2011/11/29/a_things_i_w...](http://pipeline.corante.com/archives/2011/11/29/a_things_i_wont_work_with_request.php#648176)
)

A bit more about that from a better source:
[http://www.scientificamerican.com/article/surgical-
exposure-...](http://www.scientificamerican.com/article/surgical-exposure-to-
cjd-prion/)

~~~
metasean
A couple of months after having surgery to replace a blown cervical disk, I
received a letter telling me that a prior surgical patient had died of
Creutzfeldt–Jakob and, among other things, that I may have been exposed via
surgical instruments.

My girlfriend at the time was actually really knowledgeable about
Creutzfeldt–Jakob. After many, many questions and a some more research on my
own, the one consoling thing is that if I had it, by the time the symptoms
manifested, I would be too incoherent to really understand what was happening.

While I've certainly lost some cognitive abilities in the intervening decade,
I haven't had any symptoms of Creutzfeldt-Jakob. However, I have felt
compelled to stop donating blood, and have rescinded my organ-donor status
(although I've made it clear to my family members that my body is to me made
available for research purposes).

edited: for clarity

------
alexholehouse
So the idea that neurodegeneration is essential a manifestation of protein-
specific prion disease is not a new idea[1][2][3][4][5] but is one which is
steadily gaining traction. That said, from a complexity perspective we're
still at the tip of the iceberg.

There's extensive evidence to suggest that the big, fiber-like aggregates that
form in these diseases may in fact be neuroprotective, and represent a largely
inert thermodynamic end state (basically a big inert crystal which kind of
hangs out but doesn't do much damage). More labile, smaller aggregates
(basically blobs of protein stuck together) which are formed during the fibril
formation process may in fact be more toxic, though again it really depends on
who you ask.

How the toxicity is manifest is also totally unclear - is this a loss of
function (proteins which aggregate disappear, so they can no longer do their
job), gain of function (proteins which aggregate now interact with other
things, leading to some new and bad outcomes) or somewhere in between? How
does the cellular quality control system interface with all this? Why are
certain cell types much more susceptible than others? How does the disease
spread in the brain?

There are a lot of very smart people doing some amazing work. If you're
interested, off the top of my head I'd take a look at work by Sue Lindquist,
Simon Alberti, Marc Diamond, Don Cleveland, Virginia Lee, Eric Ross, Paul
Taylor, Rick Morimoto and David Eisenberg (just to get you started!).

The one thing I would say is that I wouldn't treat this as cause for concern
for interpersonal spread. If there was a real risk of contamination from (say)
surgical instrumentation (as there was with vCJD in the UK) there would be
extensive evidence for this (just in terms of a numbers game). Which isn't to
say if you put someone's brain in your brain you won't develop the disease,
but at that point you probably have bigger issues to worry about...

In my opinion, a much more exciting story relating to ALS was published in
Cell a couple of days ago;

Patel, A., Lee, H. O., Jawerth, L., Maharana, S., Jahnel, M., Hein, M. Y., …
Alberti, S. (2015). A Liquid-to-Solid Phase Transition of the ALS Protein FUS
Accelerated by Disease Mutation. Cell, 162(5), 1066–1077.

[1]
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942086/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942086/)

[2]
[http://www.ncbi.nlm.nih.gov/pubmed/24857020](http://www.ncbi.nlm.nih.gov/pubmed/24857020)

[3]
[http://jem.rupress.org/content/209/5/889.full](http://jem.rupress.org/content/209/5/889.full)

[4]
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820001/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820001/)

------
gadders
I thought that said "porn" on first reading. So it doesn't exactly make you go
blind...

