Prion

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"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
- Prion -

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Rogue protein 'spreads in brain'
BBC Sunday, 7 June 2009
Scientists have shown a rogue protein thought to cause Alzheimer's can spread through the brain, turning healthy tissue bad. They believe the tau protein may share characteristics with the prion proteins which cause vCJD. When injected into the brains of healthy mice it triggered formation of protein tangles linked to Alzheimer's. However, experts stressed the Nature Cell Biology study did not mean tau could be passed from person to person. Tau is a protein present in all nerve cells, where it plays a key role in keeping them functioning properly. But a rogue form of the protein can trigger the formation of protein clumps within nerve cells known as neurofibrillary tangles. It is thought that these tangles are likely to be a major cause of Alzheimer's disease... Tau is a protein present in all nerve cells, where it plays a key role in keeping them functioning properly. But a rogue form of the protein can trigger the formation of protein clumps within nerve cells known as neurofibrillary tangles. It is thought that these tangles are likely to be a major cause of Alzheimer's disease.
http://news.bbc.co.uk/2/hi/health/8084787.stm

Vulnerable Brain Region May Be Central to Progression of Alzheimer's Disease
ScienceDaily (Nov. 7, 2010)
New research is helping to unravel the events that underlie the "spread" of Alzheimer's disease (AD) throughout the brain. The research, published by Cell Press in the November 4th issue of the journal Neuron, follows disease progression from a vulnerable brain region that is affected early in the disease to interconnected brain regions that are affected in later stages... "Our findings directly support the hypothesis that AD-related dysfunction is propagated through networks of neurons, with the EC as an important hub region of early vulnerability,"...
http://www.sciencedaily.com/releases/2010/11/101103135239.htm

Like a prion, Alzheimer's protein seeds itself in the brain
Misshapen amyloid-beta self-propagates in mice
By Laura Sanders
July 14th, 2012; Vol.182 #1 (p. 5)
…The most devastating kind of A-beta was that taken directly from the brains of other mice and purified, the team shows. But a synthetic version also spread, albeit slower than the brain-derived A-beta. Previous studies have hinted that A-beta acts like a prion, but no one had successfully shown that, on its own, synthetic A-beta could kick off a cascade of misfolding among the brain’s native A-beta. By demonstrating this, the researchers prove that A-beta can act as a seeding agent, says neurobiologist Mathias Jucker of the University of Tübingen in Germany. “It’s very, very beautifully shown.”..
…From the study, it’s not clear what form of A-beta is responsible for the prionlike activity. Small forms called oligomers or large clumps of fibrils could be to blame for the spreading. Nor is it known what accounts for the different potencies of the brain-derived and synthetic A-beta…
http://www.sciencenews.org/view/generic/id/341619/title/Like_a_prion,_Alzheimers_protein_seeds_itself_in_the_brain

-- Prion Mop –

Prion inhibition with multivalent PrP(Sc) binding compounds.
Mays CE, Joy S, Li L, Yu L, Genovesi S, West FG, Westaway D.
Biomaterials. 2012 Oct;33(28):6808-22. Epub 2012 Jun 28.
Source: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada.
Abstract
Quinacrine and related heterocyclic compounds have antiprion activity. Since the infectious pathogen of prion diseases is composed of multimeric PrP(Sc) assemblies, we hypothesized that this antiprion property could be enhanced by attaching multiple quinacrine-derived chloroquinoline or acridine moieties to a scaffold. In addition to exploring Congo red dye and tetraphenylporphyrin tetracarboxylic acid scaffolds, which already possess intrinsic prion-binding ability; trimesic acid was used in this role. In practice, Congo red itself could not be modified with chloroquinoline or acridine units, and a modified dicarboxyl analog was also unreactive. The latter also lacked antiprion activity in infected cultured cells. While addition of chloroquinoline to a tetraphenylporphyrin tetracarboxylic acid scaffold resulted in some reduction of PrP(Sc), moieties attached to a trimesic acid scaffold exhibited sub-micromolar IC(50)'s as well as a toxicity profile superior to quinacrine. Antiprion activity of these molecules was influenced by the length, polarity, and rigidity associated with the variable linear or cyclic polyamine tethers, and in some instances was modulated by host-cell and/or strain type. Unexpectedly, several compounds in our series increased PrP(Sc) levels. Overall, inhibitory and enhancing properties of these multivalent compounds offer new avenues for structure-based investigation of prion biology.
PMID: 22748770 [PubMed]
http://www.sciencedirect.com/science/article/pii/S0142961212006400

New Compounds Inhibit Prion Infection
ScienceDaily (July 23, 2012) — A team of University of Alberta researchers has identified a new class of compounds that inhibit the spread of prions, misfolded proteins in the brain that trigger lethal neurodegenerative diseases in humans and animals. U of A chemistry researcher Frederick West and his team have developed compounds that clear prions from infected cells derived from the brain.
http://www.sciencedaily.com/releases/2012/07/120723134856.htm
http://www.eurekalert.org/pub_releases/2012-07/uoa-uad072312.php

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