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From: TSS ()
Subject: Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity
Date: September 14, 2007 at 2:52 pm PST

Neurobiology of Disease
Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons against Prion Toxicity

Sevda Dirikoc,1 Suzette A. Priola,2 Mathieu Marella,3 Nicole Zsürger,1 and Joëlle Chabry1

1Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097, Centre National de la Recherche Scientifique, 06560 Valbonne, France, 2Laboratory of Persistent Viral Diseases, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, and 3Scripps Research Institute, La Jolla, California 92037

Correspondence should be addressed to Dr. Joëlle Chabry, Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097, Université de Nice-Sophia Antipolis, Centre National de la Recherche Scientifique, 660, route des lucioles, 06560 Valbonne, France. Email: chabry@ipmc.cnrs.fr

Prion diseases are transmissible neurodegenerative disorders characterized by the accumulation in the CNS of the protease-resistant prion protein (PrPres), a structurally misfolded isoform of its physiological counterpart PrPsen. Both neuropathogenesis and prion infectivity are related to PrPres formation. Here, we report that the nonpsychoactive cannabis constituent cannabidiol (CBD) inhibited PrPres accumulation in both mouse and sheep scrapie-infected cells, whereas other structurally related cannabinoid analogs were either weak inhibitors or noninhibitory. Moreover, after intraperitoneal infection with murine scrapie, peripheral injection of CBD limited cerebral accumulation of PrPres and significantly increased the survival time of infected mice. Mechanistically, CBD did not appear to inhibit PrPres accumulation via direct interactions with PrP, destabilization of PrPres aggregates, or alteration of the expression level or subcellular localization of PrPsen. However, CBD did inhibit the neurotoxic effects of PrPres and affected PrPres-induced microglial cell migration in a concentration-dependent manner. Our results suggest that CBD may protect neurons against the multiple molecular and cellular factors involved in the different steps of the neurodegenerative process, which takes place during prion infection. When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug.


Key words: prion; cannabinoid; neuroprotection; scrapie-infected mice; cell-free conversion; microglia

--------------------------------------------------------------------------------
Received Feb. 20, 2006; revised May 24, 2007; accepted June 13, 2007.

Correspondence should be addressed to Dr. Joëlle Chabry, Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097, Université de Nice-Sophia Antipolis, Centre National de la Recherche Scientifique, 660, route des lucioles, 06560 Valbonne, France. Email: chabry@ipmc.cnrs.fr

http://www.jneurosci.org/cgi/content/abstract/27/36/9537?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=27&issue=36&resourcetype=HWCIT

I'll Never Smoke Weed With Willie Again Lyrics
Artist(Band):Toby Keith Review The Song (2) Print the Lyrics


Artist/Band: Keith Toby
Lyrics for Song: Weed With Willie
Lyrics for Album: Shock'n Y'all
(Toby Keith/Scotty Emerick)

I always heard that his herb was top shelf
I just could not wait to find out for myself
Don't knock it til' you tried it, Well I tried it my friend
And I'll never smoke weed with Willie again

I learned a hard lesson in a small Texas town
He fired up a fat boy and passed him around
The last words that I spoke before they tucked me in
Was I'll never smoke weed with Willie again

I'll never smoke weed with Willie again
My parties all over before it begins
You can pour me some old whiskey river my friend
But I'll never smoke weed with Willie again

I hopped on his old bus, the Honey Suckle Rose
The party was Vegas it was after the show.
Alone in the front lounge with just me and him,
With one parting puff grim creeper set in.

I'll never smoke weed with Willie again
My parties all over before it begins
You can pour me some old whiskey river my friend
But I'll never smoke weed with Willie again

Now we're passing the guitar and telling good jokes
I know ones a-comin' cause I'm smelling smoke
No I do not partake, I just let it pass by
With a smile on my face and a great contact high

I'll never smoke weed with Willie again
My parties all over before it begins
You can pour me some old whiskey river my friend
But I'll never smoke weed with Willie again

In the fetal position with drool on my chin
I messed up and smoked weed with Willie again

There's a funny story about Willie and my mom I should tell you about some times. I remember (partially) his Gonzales 3 day picnic in 1976 on a 2000 acre ranch somewhere. what a picnic it was. remind me to tell you that too, we had backstage passes, old Leon and Marry Russel was there too, what a space in time it was ;-), maybe some of us are more well protected from those prions than we thought, or can remember ...TSS





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