15d-PGJ(2)

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15d-PGJ(2)

Postby dignan » Tue Apr 25, 2006 1:32 pm

Here's another one I just stumbled across that I think qualifies for pre-clinical...



Hormone regulation of microglial cell activation: relevance to multiple sclerosis.

Brain Res Brain Res Rev. 2005 Apr;48(2):322-7. Epub 2005 Jan 19.
Drew PD, Storer PD, Xu J, Chavis JA.
Department of Neurobiology and Developmental Sciences-Slot 510, University of Arkansas for Medical Sciences, Shorey Building, Little Rock, 72205, USA. drewpauld@uams.edu

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of proteins. The role of PPARs in regulating the transcription of genes involved in glucose and lipid metabolism has been extensively characterized. Interestingly, PPARs have also been demonstrated to mediate inflammatory responses. Microglia participate in pathology associated with multiple sclerosis (MS). Upon activation, microglia produce molecules including NO and TNF-alpha that can be toxic to CNS cells including myelin-producing oligodendrocytes and neurons, which are compromised in the course of MS.

Previously, we and others demonstrated that PPAR-gamma agonists including 15d-PGJ(2) are effective in the treatment of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. PPAR-gamma modulation of EAE may occur, at least in part, by inhibition of microglial cell activation.

Here, we indicate that 15d-PGJ(2) is a more potent inhibitor of microglial activation than thiazolidinediones, which are currently used to treat diabetes. Furthermore, 15d-PGJ(2) acts cooperatively with 9-cis retinoic acid, the ligand for the retinoid X receptor (RXR), in inhibiting microglial cell activation. This suggests that 15d-PGJ(2) and 9-cis RA inhibit cell activation through the formation of PPAR-gamma/RXR heterodimers. Interestingly, PGA(2), which like 15d-PGJ(2) is a cyclopentenone prostaglandin, but which unlike 15d-PGJ(2) does not bind PPAR-gamma, is a potent inhibitor of microglial cell activation.

Collectively, these studies suggest that 15d-PGJ(2) inhibits microglial cell activation by PPAR-gamma-dependent as well as PPAR - gamma - independent mechanisms. The studies further suggest that the PPAR - gamma agonist 15d-PGJ(2) in combination with retinoids may be effective in the treatment of MS.

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Postby bromley » Wed Apr 26, 2006 1:49 am

Dignan,

"15d-PGJ(2)" I think you are making up some of these drugs. What do you use - some scrabble tiles and the random number generator on a calculator?

Here's some research on IFN-Gamma

http://www.msif.org/en/research/researc ... ngamm.html


You might want to add XC-87-PKH(3.09) to pre-clinical.

Ian
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Postby dignan » Wed Apr 26, 2006 8:22 am

And isn't XC-87-PKH(3.09) so much better than XC-87-PKH( 3.08 ) ?
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Postby Arron » Wed Apr 26, 2006 10:12 am

LOL :lol: You betcha!
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Postby Degerlache » Thu Apr 27, 2006 2:45 am

Hey,

The 15D-PGJ2 thing is not really a drug, but a prostaglandin that is created naturally within our body out of arachidonic acid which itself is coming from animal fat. (What is remarkable as many natural therapies seem to avoid animal fat)

15D-PGJ2 is a natural PPARgamma agonist.

More and more research seems to come somehow at this PPARgamma thing. Is it already investigated that maybe MS sufferes might be unable to produce sufficient of this natural PPARgamma agonist 15D-PGJ2 ?

Regards,
Degerlache.
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