[quote=pegleg;871528]paula -
I'm off right now, feeling crappy, and know I should not push the submit button. But your comment singling out one person's opinion is out of order, in my humble opinion.

Lindy said ". . ., I read it a second time and found that the sentence near to the end "I'm excited........." did not fit my feelings. I am putting this one on a back burner in my mind, I really do not want to think about it"

All of us prioritize our items of opinion onto burners in our minds. The author has just put something out there to think about - you commented, gave us your thoughts and others their opinions. Why cause anyone to not feel free to also add his/her thoughts?
Respectfully,
Peggy[/quote



I'm sorry Peg,
I thanked everyone who refuted and agreed with lindy that it's best not to think about it. I didn't mean the thread should end, altho i can see how it looks like it.

As for the specifics about what you wrote, i've always said it worries me to be dealing with alpha synuclein without knowing it's function. Hopefully it will stop the disease but still no cause.

Hey wait a minute! i didn't even see your post before i typed mine!/ hope that helps...i was just starting mine when you posted.

Frankly, I have to put it on the back burner, because I have things to do and cannot afford right now to go off on a protracted research binge on prions and prion-like things. So I am grateful for Giriijas post that helps me understand a little more. But putting something on the back burner does not mean rejecting it, rather letting it stay in a place where I can process it without it stopping me in my tracks.

As far as I can see a prion like cause does not rule out many of the other things often discussed here over the years, like autoimmune response, inflammation etc. They could be effects of the cause........

Peggy, Paula, I love you both dearly, and know where you are coming from. Just can't get too off-topic....... it's just that the author has a tendency to cover all bases just in case.......

As far as I can see there is still no real explanation about how the prion like thing gets there, into our brains, I mean.

Wellll, It may be better news than you think. Consider the following-

1. Neurosci Res. 2012 Mar 23. [Epub ahead of print]

Autophagy induced by resveratrol prevents human prion protein-mediated
neurotoxicity.

Jeong JK, Moon MH, Bae BC, Lee YJ, Seol JW, Kang HS, Kim JS, Kang SJ, Park SY.

Korea Zoonoses Research Institute, Bio-Safety Research Institute, Center for
Healthcare Technology Development, College of Veterinary Medicine, Chonbuk
National University, Jeonju 561-756, South Korea.

Our previous study revealed that resveratrol blocks prion protein peptide
PrP(106-126)-induced neurotoxicity. However, the mechanism of
resveratrol-mediated neuroprotection in prion diseases is not clear. Resverstrol
initiates neuroprotective effects via the activation of autophagy, which protects
organelles, cells, and organisms against misfolded protein-disorders, including
Alzheimer's disease and Parkinson's disease via regulation of mitochondrial
homeostasis. Thus, we focused on elucidating the mechanisms responsible for
resveratrol-mediated neuroprotection related to mitochondrial homeostasis as a
result of autophagy activation. Resveratrol prevented PrP(106-126)-induced
neuronal cell death by activating autophagy. Moreover, resveratrol-induced
autophagy prevented the PrP(106-126)-induced reduction in mitochondrial potential
and translocation of Bax to the mitochondria and cytochrome c release. Our
results indicate that treatment with resveratrol appears to protect against
neurotoxicity caused by prion protein peptides and the neuroprotection is induced
by resveratrol-mediated autophagy signals.

Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All
rights reserved.

PMID: 22465415 [PubMed - as supplied by publisher]

and


1. J Pineal Res. 2012 Jan 30. doi: 10.1111/j.1600-079X.2012.00980.x. [Epub ahead of
print]

Melatonin-induced autophagy protects against human prion protein-mediated
neurotoxicity.

Jeong JK, Moon MH, Lee YJ, Seol JW, Park SY.

Korea Zoonoses Research Institute, Bio-Safety Research Institute, Center for
Healthcare Technology Development, College of Veterinary Medicine, Chonbuk
National University, Jeonju, Korea.

* Melatonin has neuroprotective effects in the models of neurodegenerative
disease including Alzheimer's and Parkinson's disease. Several studies have shown
that melatonin prevents neurodegeneration by regulation of mitochondrial
function. However, the protective action of melatonin has not been reported in
prion disease. We investigated the influence of melatonin on prion-mediated
neurotoxicity. Melatonin rescued neuronal cells from PrP(106-126)-induced
neurotoxicity by prevention of mitochondrial dysfunction. Moreover, the
protective effect of melatonin against mitochondrial dysfunction was related with
autophagy activation. Melatonin-treated cells were dose-dependently increased in
LC3-II, an autophagy marker. Melatonin-induced autophagy prevented a
PrP(106-126)-induced reduction in mitochondrial potential and translocation of
Bax to the mitochondria and cytochrome c release. On the other hand,
downregulation of autophagy protein 5 with Atg5 siRNA or the autophagy blocker
3-methyladenine prevented the melatonin-mediated neuroprotective effects. This is
the first report demonstrating that treatment with melatonin appears to protect
against prion-mediated neurotoxicity and that the neuroprotection is induced by
melatonin-mediated autophagy signals. The results of this study suggest that
regulation of melatonin is a therapeutic strategy for prion peptide-induced
apoptosis.

© 2012 John Wiley & Sons A/S.

PMID: 22335252 [PubMed - as supplied by publisher]

and



1. Front Psychiatry. 2012;3:9. Epub 2012 Feb 17.

A Medicinal Herb Scutellaria lateriflora Inhibits PrP Replication in vitro and
Delays the Onset of Prion Disease in Mice.

Eiden M, Leidel F, Strohmeier B, Fast C, Groschup MH.

Institute for Novel and Emerging Infectious Diseases,
Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health
Greifswald, Germany.

Transmissible spongiform encephalopathies (TSE) are characterized by the
misfolding of the host encoded prion protein (PrP(C)) into a pathogenic isoform
(PrP(Sc)) which leads to the accumulation of β-sheet-rich fibrils and subsequent
loss of neurons and synaptic functions. Although many compounds have been
identified which inhibit accumulation or dissolve fibrils and aggregates in vitro
there is no therapeutic treatment to stop these progressive neurodegenerative
diseases. Here we describe the effects of the traditional medicinal herb
Scutellaria lateriflora (S. lateriflora) and its natural compounds, the
flavonoids baicalein and baicalin, on the development of prion disease using in
vitro and in vivo models. S. lateriflora extract as well as both constituents
reduced the PrP(res) accumulation in scrapie-infected cell cultures and cell-free
conversion assays and lead to the destabilization of pre-existing PrP(Sc)
fibrils. Moreover, tea prepared from S. lateriflora, prolonged significantly the
incubation time of scrapie-infected mice upon oral treatment. Therefore S.
lateriflora extracts as well as the individual compounds can be considered as
promising candidates for the development of new therapeutic drugs against TSEs
and other neurodegenerative diseases like Alzheimer's and Parkinson's disease.

PMCID: PMC3281244
PMID: 22363300 [PubMed - in process]

and


1. Biochemistry. 2010 Sep 21;49(37):8127-33.

The flavanol (-)-epigallocatechin 3-gallate inhibits amyloid formation by islet
amyloid polypeptide, disaggregates amyloid fibrils, and protects cultured cells
against IAPP-induced toxicity.

Meng F, Abedini A, Plesner A, Verchere CB, Raleigh DP.

Department of Chemistry, State University of New York at Stony Brook, Stony
Brook, New York 11794-3400, USA.

Islet amyloid polypeptide (IAPP, amylin) is the major protein component of the
islet amyloid deposits associated with type 2 diabetes. The polypeptide lacks a
well-defined structure in its monomeric state but readily assembles to form
amyloid. Amyloid fibrils formed from IAPP, intermediates generated in the
assembly of IAPP amyloid, or both are toxic to β-cells, suggesting that islet
amyloid formation may contribute to the pathology of type 2 diabetes. There are
relatively few reported inhibitors of amyloid formation by IAPP. Here we show
that the tea-derived flavanol, (-)-epigallocatechin 3-gallate
[(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3-y
l 3,4,5-trihydroxybenzoate] (EGCG), is an effective inhibitor of in vitro IAPP
amyloid formation and disaggregates preformed amyloid fibrils derived from IAPP.
The compound is thus one of a very small set of molecules which have been shown
to disaggregate IAPP amyloid fibrils. Fluorescence-detected thioflavin-T binding
assays and transmission electron microscopy confirm that the compound inhibits
unseeded amyloid fibril formation as well as disaggregates IAPP amyloid. Seeding
studies show that the complex formed by IAPP and EGCG does not seed amyloid
formation by IAPP. In this regard, the behavior of IAPP is similar to the
reported interactions of Aβ and α-synuclein with EGCG. Alamar blue assays and
light microscopy indicate that the compound protects cultured rat INS-1 cells
against IAPP-induced toxicity. Thus, EGCG offers an interesting lead structure
for further development of inhibitors of IAPP amyloid formation and compounds
that disaggregate IAPP amyloid.

PMCID: PMC3199968
PMID: 20707388 [PubMed - indexed for MEDLINE]

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I do wish they would figure out whether dissolving those tangles is a good thing or not.