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PMID	18464925 ( )
Title	Regulation of Glial Cell Functions by PPAR-gamma Natural and Synthetic Agonists.
Abstract	In the recent years, the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a well known target for type II diabetes treatment, has received an increasing attention for its therapeutic potential in inflammatory and degenerative brain disorders. PPAR-gamma agonists, which include naturally occurring compounds (such as long chain fatty acids and the cyclopentenone prostaglandin 15-deoxy Delta(12,14) prostaglandin J(2)), and synthetic agonists (among which the thiazolidinediones and few nonsteroidal anti-inflammatory drugs) have shown anti-inflammatory and protective effects in several experimental models of Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, multiple sclerosis and stroke, as well as in few clinical studies. The pleiotropic effects of PPAR-gamma agonists are likely to be mediated by several mechanisms involving anti-inflammatory activities on peripheral immune cells (macrophages and lymphocytes), as well as direct effects on neural cells including cerebral vascular endothelial cells, neurons, and glia. In the present article, we will review the recent findings supporting a major role for PPAR-gamma agonists in controlling neuroinflammation and neurodegeneration through their activities on glial cells, with a particular emphasis on microglial cells as major macrophage population of the brain parenchyma and main actors in brain inflammation. 00161 Rome, Italy.

NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.

Targets by SciMiner Summary

HUGO ID	Symbol	Target Name	#Occur	ActualStr
9236	PPARG	peroxisome proliferator-activated receptor gamma	105	PPAR-G \|
9232	PPARA	peroxisome proliferator-activated receptor alpha	19	PPAR \| PPAR-ligands \| PPAR-A \| PPARs \|
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	13	COX2 \| COX-2 \| cox2 \| cox 2 \| COX-2-specific \|
6014	IL4	interleukin 4	12	IL-4 \| IL-4-induced \| il 4 \|
5992	IL1B	interleukin 1, beta	8	IL-1 \| il 1 \|
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	7	GLT-1 \| glt1 \| EAAT2 \| GLT1 \| glt 1 \|
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	6	iNOS \| nitric oxide synthase \|
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	5	ap 1 \| AP-1 \| activator protein 1 \| c fos \|
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	5	TNF-A \|
10618	CCL2	chemokine (C-C motif) ligand 2	4	monocyte chemoattractant protein 1 \| mcp 1 \| MCP-1 \|
5438	IFNG	interferon, gamma	4	IFN-G \|
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	3	amyloid \|
11362	STAT1	signal transducer and activator of transcription 1, 91kDa	3	STAT-1 \|
6871	MAPK1	mitogen-activated protein kinase 1	3	p38 \| MAP \|
4235	GFAP	glial fibrillary acidic protein	3	glial fibrillary acidic protein \| GFAP \|
9235	PPARD	peroxisome proliferator-activated receptor delta	3	FAAR \| NUC-1 \| PPAR-B \|
11005	SLC2A1	solute carrier family 2 (facilitated glucose transporter), member 1	3	GLUT-1 \|
6081	INS	insulin	2	insulin \|
6192	JAK2	Janus kinase 2 (a protein tyrosine kinase)	2	JAK2 \|
15488	IL23A	interleukin 23, alpha subunit p19	2	il 23 \| IL-23 \|
6018	IL6	interleukin 6 (interferon, beta 2)	2	IL-6 \| il 6 \|
6925	MBP	myelin basic protein	2	myelin basic protein \| MBP \|
6190	JAK1	Janus kinase 1 (a protein tyrosine kinase)	2	janus kinase 1 \| JAK1 \|
7808	NGF	nerve growth factor (beta polypeptide)	2	nerve growth factor \| NGF \|
4931	HLA-A	major histocompatibility complex, class I, A	1	MHC \|
6876	MAPK14	mitogen-activated protein kinase 14	1	p38 map kinase \|
6881	MAPK8	mitogen-activated protein kinase 8	1	Jnk \|
30880	CISD1	CDGSH iron sulfur domain 1	1	mitoneet \|
19157	IL27	interleukin 27	1	IL-27p28 \|
10477	RXRA	retinoid X receptor, alpha	1	retinoid x receptor \|
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	1	COXs \|
727	ARTN	artemin	1	neurotrophic factor \|
327	AGPS	alkylglycerone phosphate synthase	1	ADAPS \|
11848	TLR2	toll-like receptor 2	1	TLR2 \|
613	APOE	apolipoprotein E	1	apolipoprotein e \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Abstract In the recent years the peroxisome proliferator-activated receptor-_amp_#x003b3 PPAR-_amp_#x003b3 a well known target for type II diabetes treatment has
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 agonists which include naturally occurring compounds (such such as long
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The pleiotropic effects of PPAR-_amp_#x003b3 agonists are likely to be mediated by several mechanisms involving
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	will review the recent findings supporting a major role for PPAR-_amp_#x003b3 agonists in controlling neuroinflammation and neurodegeneration through their activities on
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The peroxisome proliferator-activated receptor-_amp_#x003b3 PPAR-_amp_#x003b3 belongs to the hormone nuclear receptor super family
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	the regulation of genes involved in lipid and carbohydrate metabolism PPAR-_amp_#x003b3 and the other two isoforms PPAR-_amp_#x003b1 and _amp_#x003b4 deeply affect
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR-A	2.2	lipid and carbohydrate metabolism PPAR-_amp_#x003b3 and the other two isoforms PPAR-_amp_#x003b1 and _amp_#x003b4 deeply affect lipid homeostasis and insulin sensitivity 1
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	accumulating evidence suggests that besides diabetes and metabolic syndrome 4 PPAR-_amp_#x003b3 agonists have significant therapeutic potential in brain disorders
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	of experimental studies and few clinical observations have suggested that PPAR-_amp_#x003b3 ligands may be successfully exploited to treat a wide range
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	well known model for autoimmune demyelinating diseases synthetic and natural PPAR-_amp_#x003b3 ligands_amp_#x02014 as well as some PPAR-_amp_#x003b1 or _amp_#x003b4 agonists_amp_#x02014 have
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR-A	2.2	diseases synthetic and natural PPAR-_amp_#x003b3 ligands_amp_#x02014 as well as some PPAR-_amp_#x003b1 or _amp_#x003b4 agonists_amp_#x02014 have been reported to ameliorate clinical symptoms
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	obtained in experimental models of ocular diseases have evidenced that PPAR-_amp_#x003b3 could be targeted to control inflammation and treat invalidating diseases
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	of the amount of data on the therapeutic activities of PPAR agonists in EAE clinical studies are still lacking and reports
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The beneficial effects of PPAR-_amp_#x003b3 agonists in degenerative inflammatory and traumatic brain pathologies are most
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Besides microglia PPAR-_amp_#x003b3 agonists can act on other neural cell types including astrocytes
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Several of the beneficial effects of PPAR-_amp_#x003b3 result from its ability once activated by specific ligand to
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	In addition some PPAR-_amp_#x003b3 ligands may exert specific activities independently from PPAR-_amp_#x003b3
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	addition some PPAR-_amp_#x003b3 ligands may exert specific activities independently from PPAR-_amp_#x003b3
30880	CISD1	CDGSH iron sulfur domain 1	mitoneet	1.8	I of the respiratory chain and the newly described protein mitoneet 29
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Figure 1 Cellular targets of PPAR-_amp_#x003b3 agonists in neurodegenerative diseases
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 agonists can control neuroinflammation neurodegeneration and demyelination by effecting several
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Figure 2 PPAR-_amp_#x003b3 expression in culture rat oligodendrocytes and in white matter (postnatal
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	rat OL progenitor cultures prepared as previously described 40 for PPAR-_amp_#x003b3 (more more ...
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 STRUCTURE FUNCTIONS AND AGONISTS
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The PPAR-_amp_#x003b3 and the two closely related PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR-A	2.2	The PPAR-_amp_#x003b3 and the two closely related PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also known as _amp_#x003b2 NUC-1 or FAAR
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The PPAR-_amp_#x003b3 and the two closely related PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also known as _amp_#x003b2 NUC-1 or FAAR share a
9235	PPARD	peroxisome proliferator-activated receptor delta	NUC-1	2.7	closely related PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also known as _amp_#x003b2 NUC-1 or FAAR share a high homology but differ for tissue
9235	PPARD	peroxisome proliferator-activated receptor delta	FAAR	2.7	PPAR-_amp_#x003b1 and PPAR-_amp_#x003b4 (also also known as _amp_#x003b2 NUC-1 or FAAR share a high homology but differ for tissue distribution and
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR-A	2.2	PPAR-_amp_#x003b1 is mainly expressed in tissues with high catabolic rates of
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	fatty acids such as the liver muscle and heart whereas PPAR-_amp_#x003b4 shows a much wider distribution
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 is highly expressed in adipose tissue and in cells of
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	In the brain PPAR-_amp_#x003b3 is expressed in several cell types including microglia astrocytes oligodendrocytes
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 protein shows a remarkable conservation across species
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Human and the murine PPAR-_amp_#x003b3 proteins show 95% identity at the amino acid level
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The human PPAR-_amp_#x003b3 gene is located on chromosome 3 and generates at least
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	on chromosome 3 and generates at least three mRNA transcripts PPAR-_amp_#x003b3 1 PPAR-_amp_#x003b3 2 and PPAR-_amp_#x003b3 3 30 _amp_#x02013 32
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	3 and generates at least three mRNA transcripts PPAR-_amp_#x003b3 1 PPAR-_amp_#x003b3 2 and PPAR-_amp_#x003b3 3 30 _amp_#x02013 32
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	at least three mRNA transcripts PPAR-_amp_#x003b3 1 PPAR-_amp_#x003b3 2 and PPAR-_amp_#x003b3 3 30 _amp_#x02013 32
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 1 e PPAR-_amp_#x003b3 3 mRNAs encode for the same protein
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 1 e PPAR-_amp_#x003b3 3 mRNAs encode for the same protein while PPAR-_amp_#x003b3 2
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	e PPAR-_amp_#x003b3 3 mRNAs encode for the same protein while PPAR-_amp_#x003b3 2 mRNA gives rise to a protein containing 28 additional
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.2	At protein level all three PPARs show a similar organization in five different functional domains two
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.2	hydrophobic domains of the ligand explains the low ligand-specificity of PPARs
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	Nonetheless the LBDs of the three PPAR isotypes have sufficiently divergent amino acid sequences to allow some
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	Several unsaturated fatty acids bind to all three PPAR isoforms whereas saturated fatty acids are in general poor PPAR
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	PPAR isoforms whereas saturated fatty acids are in general poor PPAR ligands
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	However given the relatively high concentration of lipids required for PPAR activation (in in the micromolar or submicromolar concentration range their
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	or submicromolar concentration range their _amp_#x0201c in vivo_amp_#x0201d role as PPAR ligands remains a controversial issue
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Some arachidonic acid metabolites are more effective PPAR-_amp_#x003b3 ligands than the precursor
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	_amp_#x003b2 -unsaturated ketone in the cyclopentenone ring was the first PPAR-_amp_#x003b3 endogenous ligand described in 1995 by two independent groups 33
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The implication of PPAR-_amp_#x003b3 in several important metabolic and degenerative disorders has strongly pushed
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	and degenerative disorders has strongly pushed the research of specific PPAR-_amp_#x003b3 agonists and antagonist (for for review see 35
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	A major group of synthetic PPAR-_amp_#x003b3 agonists is represented by the antidiabetic drugs TZDs originally identified
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	A different series of synthetic PPAR-_amp_#x003b3 ligands are derived by L-tyrosine GI262570 GW1929 and GW7845 which
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	were developed on the basis of their activity on human PPAR-_amp_#x003b3 and are among the most potent PPAR-_amp_#x003b3 agonists being active
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	activity on human PPAR-_amp_#x003b3 and are among the most potent PPAR-_amp_#x003b3 agonists being active at low nanomolar concentrations
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.2	the heterogeneous NSAID family have been described as agonists for PPARs 35 and reference therein
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	In most cases the doses required for PPAR-_amp_#x003b3 agonist activity are in the high micromolar range thus largely
2294	COX8A	cytochrome c oxidase subunit 8A (ubiquitous)	COXs	0.0	exceeding those required for in vivo inhibition of cyclooxygenases (COXs), COXs the main target of these drugs
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	or paracetamol lack of agonistic activity for any of the PPAR subtypes whereas indomethacin ibuprofen and diclofenac are selective for the
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	flurbiprofen HCT1026 and NXC 2216 were both able to activate PPAR-_amp_#x003b3 and induce its specific binding to a PPRE sequence 36
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 AGONISTS AND OLIGODENDROCYTE BIOLOGY
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.2	Given the role of PPARs in lipid metabolism it is conceivable that this group of
9235	PPARD	peroxisome proliferator-activated receptor delta	PPAR-B	2.2	Although PPAR-_amp_#x003b2 / _amp_#x003b4 has been long considered the PPAR type mainly
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	Although PPAR-_amp_#x003b2 / _amp_#x003b4 has been long considered the PPAR type mainly expressed in OLs and involved in myelination 43
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	myelination 43 44 recent findings support an important role for PPAR-_amp_#x003b3 activators in OL protection and differentiation
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The first evidence for a role of PPAR-_amp_#x003b3 in OL differentiation was reported by Roth et al 45
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	the authors first demonstrated that these cells expressed all three PPAR isoforms and found that natural and synthetic PPAR-_amp_#x003b3 agonists but
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	all three PPAR isoforms and found that natural and synthetic PPAR-_amp_#x003b3 agonists but not other isoform activators enhance process extension and
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	These effects were blocked by the PPAR-_amp_#x003b3 antagonist GW9662
327	AGPS	alkylglycerone phosphate synthase	ADAPS	0.3	was accompanied by enhanced expression of alkyl-dihydroxyacetone phosphate synthase (ADAPS), ADAPS a peroxisomal enzyme required for the synthesis of plasmalogen an
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	These observations suggest that PPAR-_amp_#x003b3 mediated mechanisms may be important for OL differentiation and peroxisome
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	In line with the proposed role of PPAR-_amp_#x003b3 in controlling OL differentiation and functions we have recently confirmed
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	differentiation and functions we have recently confirmed the expression of PPAR-_amp_#x003b3 in highly purified rat OL cultures ( Figure 2 (a))
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	In addition we found an increased expression of PPAR-_amp_#x003b3 in white matter of young rats (post post natal day
6925	MBP	myelin basic protein	MBP	1.9	indicated by the strong reduction of myelin basic protein (MBP) MBP expression ( Figure 2 (b)) b
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Whether PPAR-_amp_#x003b3 over-expression is part of an adaptive response to the hypoxic
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 AGONISTS AND OLIGODENDROCYTE BIOLOGY
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	the above findings Xiang et al 49 reported that the PPAR-_amp_#x003b3 natural ligand 15d-PGJ 2 but not other PGs induced apoptosis
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	cultures 50 cell death was independent of the nuclear receptor PPAR-_amp_#x003b3
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 AGONISTS AND ASTROCYTES
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	characterized by increased expression of glial fibrillary acidic protein (GFAP), GFAP a constituent of the intermediate filaments are typical of most
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Astrocytes express PPAR-_amp_#x003b3 53 54 and accumulating evidence over the last ten years
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	and accumulating evidence over the last ten years indicates that PPAR-_amp_#x003b3 agonists modulate astrocyte functions
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	in time- and dose-dependent manners through a mechanism independent of PPAR-_amp_#x003b3 and involving cAMP/PKA cAMP PKA signaling 55
11005	SLC2A1	solute carrier family 2 (facilitated glucose transporter), member 1	GLUT-1	2.3	Pioglitazone did not modify the expression of the glucose transporter GLUT-1 which is mainly expressed in glial and endothelial cells but
11005	SLC2A1	solute carrier family 2 (facilitated glucose transporter), member 1	GLUT-1	2.3	endothelial cells but rather it increased glucose flux through pre-existing GLUT-1 protein
11005	SLC2A1	solute carrier family 2 (facilitated glucose transporter), member 1	GLUT-1	2.3	intracellular glucose levels are replenished by glucose transport through the GLUT-1
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Another important mechanism by which PPAR-_amp_#x003b3 agonists could exert neuroprotection by influencing astrocyte functions is the
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Romera et al 56 reported that the PPAR-_amp_#x003b3 antagonists T0070907 prevented the ischemic preconditioning-induced (IPC) IPC neuroprotection in
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	GLT-1	2.8	agonist L-796 449 induced a concentration-dependent increase in glutamate transporter GLT-1 expression and 3 H glutamate uptake in rat astrocytes
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	GLT1	3.1	identified six putative PPREs in the promoter region of GLT1/EAAT2 GLT1 EAAT2 gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	EAAT2	3.3	six putative PPREs in the promoter region of GLT1/EAAT2 GLT1 EAAT2 gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a novel
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	GLT1	3.1	the promoter region of GLT1/EAAT2 GLT1 EAAT2 gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a novel PPAR-_amp_#x003b3 target gene 56
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	EAAT2	3.3	promoter region of GLT1/EAAT2 GLT1 EAAT2 gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a novel PPAR-_amp_#x003b3 target gene 56
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	gene suggesting GLT1/EAAT2 GLT1 EAAT2 glutamate transporter is a novel PPAR-_amp_#x003b3 target gene 56
7808	NGF	nerve growth factor (beta polypeptide)	NGF	1.2	synthesis and release of neurotrophic factor nerve growth factor (NGF) NGF in mouse primary astrocytes which could further contribute to neuroprotection
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Such neurotoxic activities have been shown to be reduced by PPAR-_amp_#x003b3 agonists in several experimental paradigms
6018	IL6	interleukin 6 (interferon, beta 2)	IL-6	1.6	reported to inhibit the production of nitric oxide (NO), NO IL-6 and TNF-_amp_#x003b1 as well as expression of the inducible enzymes
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-A	0.3	inhibit the production of nitric oxide (NO), NO IL-6 and TNF-_amp_#x003b1 as well as expression of the inducible enzymes iNOS and
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.2	and TNF-_amp_#x003b1 as well as expression of the inducible enzymes iNOS and COX2 induced in LPS-stimulated astrocyte and microglial cultures 58
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX2	2.5	as well as expression of the inducible enzymes iNOS and COX2 induced in LPS-stimulated astrocyte and microglial cultures 58
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	in vivo effects were substantially attenuated by cotreatment with the PPAR-_amp_#x003b3 antagonist GW9662 supporting the involvement of PPAR-_amp_#x003b3 activation
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	cotreatment with the PPAR-_amp_#x003b3 antagonist GW9662 supporting the involvement of PPAR-_amp_#x003b3 activation
5992	IL1B	interleukin 1, beta	IL-1	1.3	above described TZDs the natural ligand 15d-PGJ 2 prevented the IL-1 _amp_#x003b2 -induced COX-2 mRNA accumulation in human astrocytes through a
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	3.0	the natural ligand 15d-PGJ 2 prevented the IL-1 _amp_#x003b2 -induced COX-2 mRNA accumulation in human astrocytes through a PPAR _amp_#x003b3 -independent
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	2.8	_amp_#x003b2 -induced COX-2 mRNA accumulation in human astrocytes through a PPAR _amp_#x003b3 -independent mechanism 60
6871	MAPK1	mitogen-activated protein kinase 1	MAP	2.2	colleagues 61 showed that ciglitazone and 15d-PGJ 2 activated the MAP kinase cascades (Erk, Erk Jnk and p38 MAP kinase in
6881	MAPK8	mitogen-activated protein kinase 8	Jnk	1.2	and 15d-PGJ 2 activated the MAP kinase cascades (Erk, Erk Jnk and p38 MAP kinase in astrocytes by a PPAR-_amp_#x003b3 independent
6871	MAPK1	mitogen-activated protein kinase 1	p38	2.2	2 activated the MAP kinase cascades (Erk, Erk Jnk and p38 MAP kinase in astrocytes by a PPAR-_amp_#x003b3 independent mechanism which
6871	MAPK1	mitogen-activated protein kinase 1	MAP	2.2	activated the MAP kinase cascades (Erk, Erk Jnk and p38 MAP kinase in astrocytes by a PPAR-_amp_#x003b3 independent mechanism which required
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Erk Jnk and p38 MAP kinase in astrocytes by a PPAR-_amp_#x003b3 independent mechanism which required the presence of ROS
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Again independently of PPAR-_amp_#x003b3 15d-PGJ 2 and rosiglitazone reduced the phosphorylation of signal transducers
11362	STAT1	signal transducer and activator of transcription 1, 91kDa	STAT	1.2	the phosphorylation of signal transducers and activators of transcription (STAT) STAT 1 and 3 as well as Janus kinase 1 (JAK1)
6190	JAK1	Janus kinase 1 (a protein tyrosine kinase)	JAK1	1.2	1 and 3 as well as Janus kinase 1 (JAK1) JAK1 and JAK2 in activated astrocytes and microglia 62
6192	JAK2	Janus kinase 2 (a protein tyrosine kinase)	JAK2	0.9	1 and 3 as well as Janus kinase 1 (JAK1) JAK1 and JAK2 in activated astrocytes and microglia 62
6192	JAK2	Janus kinase 2 (a protein tyrosine kinase)	JAK2	0.9	3 as well as Janus kinase 1 (JAK1) JAK1 and JAK2 in activated astrocytes and microglia 62
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR-ligands	2.2	Drew 63 extended the analysis of the anti-inflammatory activity of PPAR-ligands to other inflammatory mediators belonging to the IL-12 family of
15488	IL23A	interleukin 23, alpha subunit p19	IL-23	1.3	that in primary astrocytes LPS induced the production of IL-12p40 IL-23 and IL-27p28 proteins which was significantly reduced in the presence
19157	IL27	interleukin 27	IL-27p28	0.8	primary astrocytes LPS induced the production of IL-12p40 IL-23 and IL-27p28 proteins which was significantly reduced in the presence of 15d-PGJ
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	multiple sclerosis this observation further support the potential role of PPAR-_amp_#x003b3 agonists in MS treatment 5 64
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	In line with the beneficial effect of PPAR-_amp_#x003b3 agonists in experimental models of inflammatory diseases PPAR-_amp_#x003b3 has also
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	effect of PPAR-_amp_#x003b3 agonists in experimental models of inflammatory diseases PPAR-_amp_#x003b3 has also been involved in anti-inflammatory functions of IL-4 a
6014	IL4	interleukin 4	IL-4	1.3	diseases PPAR-_amp_#x003b3 has also been involved in anti-inflammatory functions of IL-4 a Th2 type cytokine which plays an important role in
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.2	Paintlia et al 65 demonstrated that the inhibition of iNOS expression and the increase of survival of differentiating OPs induced
6014	IL4	interleukin 4	IL-4	1.3	and the increase of survival of differentiating OPs induced by IL-4 in inflammatory cytokine-stimulated mixed cultures are mediated by PPAR-_amp_#x003b3 activation
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	by IL-4 in inflammatory cytokine-stimulated mixed cultures are mediated by PPAR-_amp_#x003b3 activation
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	authors describe a coordinate increase in the expression of both PPAR-_amp_#x003b3 and its natural ligand-producing enzyme 12/15-lipoxygenase 12 15-lipoxygenase (12/15-LOX) 12
6014	IL4	interleukin 4	IL-4-induced	1.3	(12/15-LOX) 12 15-LOX in IL-4-treated glial cells and show that IL-4-induced PPAR-_amp_#x003b3 activation antagonizes NF-_amp_#x003ba B transactivation in inflammatory cytokine-stimulated astrocytes
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	12 15-LOX in IL-4-treated glial cells and show that IL-4-induced PPAR-_amp_#x003b3 activation antagonizes NF-_amp_#x003ba B transactivation in inflammatory cytokine-stimulated astrocytes
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	A similar upregulation of PPAR-_amp_#x003b3 by IL-4 was demonstrated in cultured microglial cells 66
6014	IL4	interleukin 4	IL-4	1.3	A similar upregulation of PPAR-_amp_#x003b3 by IL-4 was demonstrated in cultured microglial cells 66
6014	IL4	interleukin 4	IL-4	1.3	To link between IL-4 and PPAR-_amp_#x003b3 is completed by the observation that the anti-inflammatory
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	To link between IL-4 and PPAR-_amp_#x003b3 is completed by the observation that the anti-inflammatory activity of
6014	IL4	interleukin 4	IL-4	1.3	the TZD troglitazone was mediated by its ability to increase IL-4 expression in glial cultures 67
5992	IL1B	interleukin 1, beta	IL-1	1.3	recent study 15d-PGJ 2 and ciglitazone suppress the production of IL-1 _amp_#x003b2 and NO in Staphylococcus aureus-stimulated astrocytes 68
11848	TLR2	toll-like receptor 2	TLR2	0.3	Interestingly 15d-PGJ 2 attenuated TLR2 expression the PPR recognizing Staphylococcus aureus
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	the release of proinflammatory mediators induced by Staphylococcus aureus in PPAR-_amp_#x003b3 -deficient astrocytes supporting PPAR-_amp_#x003b3 -independent effects of these compounds
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	mediators induced by Staphylococcus aureus in PPAR-_amp_#x003b3 -deficient astrocytes supporting PPAR-_amp_#x003b3 -independent effects of these compounds
4235	GFAP	glial fibrillary acidic protein	GFAP	2.5	At noncytotoxic concentrations OTA down-regulated GFAP expression while it upregulated vimentin
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Interestingly OTA increased PPAR-_amp_#x003b3 expression possibly increasing the susceptibility of OTA-exposed cells to PPAR-_amp_#x003b3
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 expression possibly increasing the susceptibility of OTA-exposed cells to PPAR-_amp_#x003b3 agonist treatment 69
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	PPAR-_amp_#x003b3 AGONISTS AND MICROGLIAL CELLS
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	In this view PPAR-_amp_#x003b3 agonists have been extensively studied in the last decade for
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	provided by Petrova et al 74 who demonstrated that this PPAR-_amp_#x003b3 natural ligand attenuates iNOS expression and the subsequent NO accumulation
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.2	al 74 who demonstrated that this PPAR-_amp_#x003b3 natural ligand attenuates iNOS expression and the subsequent NO accumulation in the murine BV-2
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.2	the NO pathway it was suggested that 15d-PGJ 2 inhibits iNOS expression by a PPAR-_amp_#x003b3 independent mechanism
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	was suggested that 15d-PGJ 2 inhibits iNOS expression by a PPAR-_amp_#x003b3 independent mechanism
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-A	0.3	authors then demonstrated that 15d-PGJ 2 decreases the production of TNF-_amp_#x003b1 IL-1 _amp_#x003b2 and the expression of COX-2 in the same
5992	IL1B	interleukin 1, beta	IL-1	1.3	then demonstrated that 15d-PGJ 2 decreases the production of TNF-_amp_#x003b1 IL-1 _amp_#x003b2 and the expression of COX-2 in the same cell
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	3.0	the production of TNF-_amp_#x003b1 IL-1 _amp_#x003b2 and the expression of COX-2 in the same cell system while increasing the expression of
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	first time that primary microglial cells unlike BV-2 cells express PPAR-_amp_#x003b3 and that such basal expression is increased by its specific
5438	IFNG	interferon, gamma	IFN-G	0.3	in the presence of microglial activators such as LPS and IFN-_amp_#x003b3
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Microglial PPAR-_amp_#x003b3 was subsequently shown to be functionally active being able to
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	2.2	cell line in primary microglial cultures 15d-PGJ 2 prevented LPS-induced iNOS expression and TNF-_amp_#x003b1 production as well as IFN-_amp_#x003b3 -induced expression
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-A	0.3	primary microglial cultures 15d-PGJ 2 prevented LPS-induced iNOS expression and TNF-_amp_#x003b1 production as well as IFN-_amp_#x003b3 -induced expression of major histocompatibility
5438	IFNG	interferon, gamma	IFN-G	0.3	prevented LPS-induced iNOS expression and TNF-_amp_#x003b1 production as well as IFN-_amp_#x003b3 -induced expression of major histocompatibility complex (MHC) MHC class II
4931	HLA-A	major histocompatibility complex, class I, A	MHC	1.8	well as IFN-_amp_#x003b3 -induced expression of major histocompatibility complex (MHC) MHC class II antigens by mechanisms involving PPAR-_amp_#x003b3 activation and reduced
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	histocompatibility complex (MHC) MHC class II antigens by mechanisms involving PPAR-_amp_#x003b3 activation and reduced activation of STAT-1 and NF-_amp_#x003ba B which
11362	STAT1	signal transducer and activator of transcription 1, 91kDa	STAT-1	1.2	antigens by mechanisms involving PPAR-_amp_#x003b3 activation and reduced activation of STAT-1 and NF-_amp_#x003ba B which are known to mediate IFN-_amp_#x003b3 and
5438	IFNG	interferon, gamma	IFN-G	0.3	of STAT-1 and NF-_amp_#x003ba B which are known to mediate IFN-_amp_#x003b3 and LPS signaling 76
11362	STAT1	signal transducer and activator of transcription 1, 91kDa	STAT-1	1.2	did not affect NF-_amp_#x003ba B binding activity although it decreased STAT-1 expression and enhanced expression and binding activity of the AP-1
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	AP-1	2.8	STAT-1 expression and enhanced expression and binding activity of the AP-1 proteins J-Jun and c-Fos 60
5438	IFNG	interferon, gamma	IFN-G	0.3	N9 activated either by LPS alone or in combination with IFN-_amp_#x003b3 or TNF-_amp_#x003b1 63 77 15d-PGJ 2 attenuated microglial activation also
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-A	0.3	either by LPS alone or in combination with IFN-_amp_#x003b3 or TNF-_amp_#x003b1 63 77 15d-PGJ 2 attenuated microglial activation also when elicited
10618	CCL2	chemokine (C-C motif) ligand 2	MCP-1	2.6	of proinflammatory cytokines and the chemokine monocyte chemoattractant protein-1 (MCP-1) MCP-1 73 78
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	2 ciglitazone and troglitazone prevented LPS-induced neuronal death suggesting a PPAR-_amp_#x003b3 mediated mechanism of neuroprotection 79
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.0	ibuprofen reduced the neurotoxicity of microglial cells exposed to _amp_#x003b2 -amyloid fibrils 80
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2-specific	2.5	In this cell system COX-2-specific inhibitors failed to promote neuronal survival suggesting protective mechanisms independent
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	3.0	failed to promote neuronal survival suggesting protective mechanisms independent of COX-2 metabolism
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	NXC 2216 were able to prevent microglial activation by activating PPAR-_amp_#x003b3 36 37
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Interestingly NCX 2216 after an initial activation induced PPAR-_amp_#x003b3 nitration and inactivation
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	TNF-A	0.3	These effects were paralleled by a transient reduction of TNF-_amp_#x003b1 and NO production and a protracted inhibition of IL-1 _amp_#x003b2
5992	IL1B	interleukin 1, beta	IL-1	1.3	of TNF-_amp_#x003b1 and NO production and a protracted inhibition of IL-1 _amp_#x003b2 and PGE 2 synthesis suggesting a dynamic regulation of
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	NCX 2216 could therefore lead after an initial activation of PPAR-_amp_#x003b3 to a protracted suppression of its control over microglial activation
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.0	2216 in an AD animal model the reduction of cerebral amyloid load accompanied by a sustained microglial activation 82
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The contribution of PPAR-_amp_#x003b3 -dependent or independent mechanisms to the inhibition of microglial activation
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	2 at concentrations several fold lower than those required for PPAR-_amp_#x003b3 activation effectively reduced the LPS-stimulated production of PGJ 2 by
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	3.0	of PGJ 2 by directly preventing the enzymatic activity of COX-2 rather than its expression as previously described in activated monocytic
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	3.0	The reduction of COX-2 enzymatic activity could be achieved through the modifications of key
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	At concentration 10 times higher than those required to activate PPAR-_amp_#x003b3 15d-PGJ 2 induced microglial cell impairment and death by apoptosis
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	the link between the proapoptotic effect of 15d-PGJ 2 and PPAR-_amp_#x003b3 activation is still controversial
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	and human and rat glioma cell lines appears mediated by PPAR-_amp_#x003b3 -dependent mechanisms 61 87 89 _amp_#x02013 91
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	an increasing number of experimental studies supporting the use of PPAR-_amp_#x003b3 ligands to treat major disabling brain diseases with a high
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	in animal models of AD due to the ability of PPAR-_amp_#x003b3 agonists to reduced inflammation and the amyloid burden by various
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.0	the ability of PPAR-_amp_#x003b3 agonists to reduced inflammation and the amyloid burden by various mechanisms have found some validation in a
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Similarly the better neurological outcome reported after administration of PPAR-_amp_#x003b3 ligands in experimental stroke models are consistent with the result
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	The clinical use of PPAR-_amp_#x003b3 agonists in MS and ASL remains poorly investigated
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Although PPAR-_amp_#x003b3 synthetic ligands such as TZDs and NSAIDs appear to be
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	Among these the toxic effect associated with some PPAR-_amp_#x003b3 agonists and their blood-brain-barrier permeability which are at present still
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	A deep knowledge of the molecular mechanisms evoked by PPAR-_amp_#x003b3 ligands either dependent or independent of the receptor activation and
9236	PPARG	peroxisome proliferator-activated receptor gamma	PPAR-G	2.2	the specific cell type is mandatory for the development of PPAR-_amp_#x003b3 drugs with increasing efficacy and safety
6081	INS	insulin	insulin	1.0	ir role in the regulation of genes involved in lipid and carbohydrate metabolism ppar _amp_#x003b3; and the other two isoforms ppar _amp_#x003b1; and _amp_#x003b4; deeply affect lipid homeostasis and insulin sensitivity [ 1 _amp_#x02013; 3 ].
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	activator protein 1	1.0	15d pj 2 = 15 deoxy _amp_#x00394; 12 14 prostaglandin j 2 ad= alzheimer disease als= amyotrophic lateral sclerosis ap 1= activator protein 1 cns= central nervous system cox= cyclooxygenase dbd= dna binding domain eae= experimental autoimmune encephalomyelitis hode= hydroxy octadecadienoic acids ifn= interferon il= interleukin inos= induci
10618	CCL2	chemokine (C-C motif) ligand 2	mcp 1	1.0	noic acids ifn= interferon il= interleukin inos= inducible nitric oxide synthase jak= janus activated kinases lbd= ligand binding domain lps= lipopolysaccharide mapk= mitogen activated protein kinase mcp 1= monocyte chemoattractrant protein 1 mhc= major histocompatibility complex ms= multiple sclerosis nf _amp_#x003ba; b= nuclear factor _amp_#x003ba; b no= nitric oxide nsaids= nonsteroidal anti inflamm
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	ap 1	1.0	15d pj 2 = 15 deoxy _amp_#x00394; 12 14 prostaglandin j 2 ad= alzheimer disease als= amyotrophic lateral sclerosis ap 1= activator protein 1 cns= central nervous system cox= cyclooxygenase dbd= dna binding domain eae= experimental autoimmune encephalomyelitis hode= hydroxy octadecadienoic acids ifn= interferon il= int
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	= central nervous system cox= cyclooxygenase dbd= dna binding domain eae= experimental autoimmune encephalomyelitis hode= hydroxy octadecadienoic acids ifn= interferon il= interleukin inos= inducible nitric oxide synthase jak= janus activated kinases lbd= ligand binding domain lps= lipopolysaccharide mapk= mitogen activated protein kinase mcp 1= monocyte chemoattractrant protein 1 mhc= major histocompatibility complex
10477	RXRA	retinoid X receptor, alpha	retinoid x receptor	1.0	rxr= retinoid x receptor socs= suppressor of cytokine signalling stat= signal transducer and activators of transcription th= t helper cell tnf= tumour necrosis factor tzds= thiazolidinediones
6081	INS	insulin	insulin	1.0	a major group of synthetic ppar _amp_#x003b3; agonists is represented by the antidiabetic drugs tzds originally identified for their ability to improve the insulin sensitivity of diabetic animals.
6925	MBP	myelin basic protein	myelin basic protein	1.0	and delayed brain damage in the newborn [ 47 48 ] and is characterized by early oxidative stress delayed behavioral deficits and alteration in myelin formation as indicated by the strong reduction of myelin basic protein mbp expression figure 2 b .
4235	GFAP	glial fibrillary acidic protein	glial fibrillary acidic protein	1.0	reactive astrocytes which are characterized by increased expression of glial fibrillary acidic protein gfap a constituent of the intermediate filaments are typical of most brain pathologies.
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	glt 1	1.0	in addition rosiglitazone and the non tzd agonist l 796 449 induced a concentration dependent increase in glutamate transporter glt 1 expression and [ 3 h] glutamate uptake in rat astrocytes.
10940	SLC1A2	solute carrier family 1 (glial high affinity glutamate transporter), member 2	glt1	1.0	in addition the authors identified six putative ppres in the promoter region of glt1/eaat2 gene suggesting glt1/eaat2 glutamate transporter is a novel ppar _amp_#x003b3; target gene [ 56 ].
727	ARTN	artemin	neurotrophic factor	1.0	finally 15d pgj 2 remarkably increase the synthesis and release of neurotrophic factor nerve growth factor ngf in mouse primary astrocytes which could further contribute to neuroprotection [ 57 ].
7808	NGF	nerve growth factor (beta polypeptide)	nerve growth factor	1.0	finally 15d pgj 2 remarkably increase the synthesis and release of neurotrophic factor nerve growth factor ngf in mouse primary astrocytes which could further contribute to neuroprotection [ 57 ].
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox2	1.0	the two tzd compounds np00111 and np01138 were reported to inhibit the production of nitric oxide no il 6 and tnf _amp_#x003b1; as well as expression of the inducible enzymes inos and cox2 induced in lps stimulated astrocyte and microglial cultures [ 58 ].
6018	IL6	interleukin 6 (interferon, beta 2)	il 6	1.0	the two tzd compounds np00111 and np01138 were reported to inhibit the production of nitric oxide no il 6 and tnf _amp_#x003b1; as well as expression of the inducible enzymes inos and cox2 induced in lps stimulated astrocyte and microglial cultures [ 58 ].
5992	IL1B	interleukin 1, beta	il 1	1.0	in contrast to the above described tzds the natural ligand 15d pgj 2 prevented the il 1 _amp_#x003b2; induced cox 2 mrna accumulation in human astrocytes through a ppar _amp_#x003b3; independent mechanism [ 60 ].
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox 2	1.0	in contrast to the above described tzds the natural ligand 15d pgj 2 prevented the il 1 _amp_#x003b2; induced cox 2 mrna accumulation in human astrocytes through a ppar _amp_#x003b3; independent mechanism [ 60 ].
6876	MAPK14	mitogen-activated protein kinase 14	p38 map kinase	1.0	similarly lennon and colleagues [ 61 ] showed that ciglitazone and 15d pgj 2 activated the map kinase cascades erk jnk and p38 map kinase in astrocytes by a ppar _amp_#x003b3; independent mechanism which required the presence of ros.
6190	JAK1	Janus kinase 1 (a protein tyrosine kinase)	janus kinase 1	1.0	again independently of ppar _amp_#x003b3; 15d pgj 2 and rosiglitazone reduced the phosphorylation of signal transducers and activators of transcription stat 1 and 3 as well as janus kinase 1 jak1 and jak2 in activated astrocytes and microglia [ 62 ].
15488	IL23A	interleukin 23, alpha subunit p19	il 23	1.0	they found that in primary astrocytes lps induced the production of il 12p40 il 23 and il 27p28 proteins which was significantly reduced in the presence of 15d pgj 2 .
6014	IL4	interleukin 4	il 4	1.0	in line with the beneficial effect of ppar _amp_#x003b3; agonists in experimental models of inflammatory diseases ppar _amp_#x003b3; has also been involved in anti inflammatory functions of il 4 a th2 type cytokine which plays an important role in controlling th1 cell responses and resolution of inflammation.
6014	IL4	interleukin 4	il 4	1.0	paintlia et al. [ 65 ] demonstrated that the inhibition of inos expression and the increase of survival of differentiating ops induced by il 4 in inflammatory cytokine stimulated mixed cultures are mediated by ppar _amp_#x003b3; activation.
6014	IL4	interleukin 4	il 4	1.0	in support of their conclusions the authors describe a coordinate increase in the expression of both ppar _amp_#x003b3; and its natural ligand producing enzyme 12/15 lipoxygenase 12/15 lox in il 4 treated glial cells and show that il 4 induced ppar _amp_#x003b3; activation antagonizes nf _amp_#x003ba; b transactivation in inflammatory cytokine stimulated astrocytes.
6014	IL4	interleukin 4	il 4	1.0	treated glial cells and show that il 4 induced ppar _amp_#x003b3; activation antagonizes nf _amp_#x003ba; b transactivation in inflammatory cytokine stimulated astrocytes.
6014	IL4	interleukin 4	il 4	1.0	a similar upregulation of ppar _amp_#x003b3; by il 4 was demonstrated in cultured microglial cells [ 66 ].
6014	IL4	interleukin 4	il 4	1.0	to link between il 4 and ppar _amp_#x003b3; is completed by the observation that the anti inflammatory activity of the tzd troglitazone was mediated by its ability to increase il 4 expression in glial cultures [ 67 ].
5992	IL1B	interleukin 1, beta	il 1	1.0	in a recent study 15d pgj 2 and ciglitazone suppress the production of il 1 _amp_#x003b2; and no in staphylococcus aureus stimulated astrocytes [ 68 ].
5992	IL1B	interleukin 1, beta	il 1	1.0	the same authors then demonstrated that 15d pgj 2 decreases the production of tnf _amp_#x003b1; il 1 _amp_#x003b2; and the expression of cox 2 in the same cell system while increasing the expression of the antioxidant enzyme hemeoxygenase 1 and the intracellular levels of glutathione [ 75 ].
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox 2	1.0	the same authors then demonstrated that 15d pgj 2 decreases the production of tnf _amp_#x003b1; il 1 _amp_#x003b2; and the expression of cox 2 in the same cell system while increasing the expression of the antioxidant enzyme hemeoxygenase 1 and the intracellular levels of glutathione [ 75 ].
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	ap 1	1.0	in human microglial cells 15d pgj 2 did not affect nf _amp_#x003ba; b binding activity although it decreased stat 1 expression and enhanced expression and binding activity of the ap 1 proteins j jun and c fos [ 60 ].
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	c fos	1.0	human microglial cells 15d pgj 2 did not affect nf _amp_#x003ba; b binding activity although it decreased stat 1 expression and enhanced expression and binding activity of the ap 1 proteins j jun and c fos [ 60 ].
10618	CCL2	chemokine (C-C motif) ligand 2	mcp 1	1.0	microglial activation also when elicited by gram positive bacteria staphylococcus aureus by inhibiting the expression of proinflammatory cytokines and the chemokine monocyte chemoattractant protein 1 mcp 1 [ 73 78 ].
10618	CCL2	chemokine (C-C motif) ligand 2	monocyte chemoattractant protein 1	1.0	1; [ 63 77 ]. 15d pgj 2 attenuated microglial activation also when elicited by gram positive bacteria staphylococcus aureus by inhibiting the expression of proinflammatory cytokines and the chemokine monocyte chemoattractant protein 1 mcp 1 [ 73 78 ].
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox 2	1.0	in this cell system cox 2 specific inhibitors failed to promote neuronal survival suggesting protective mechanisms independent of cox 2 metabolism.
5992	IL1B	interleukin 1, beta	il 1	1.0	these effects were paralleled by a transient reduction of tnf _amp_#x003b1; and no production and a protracted inhibition of il 1 _amp_#x003b2; and pge 2 synthesis suggesting a dynamic regulation of the functional state of activated microglia by ncx 2216.
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox 2	1.0	at concentrations several fold lower than those required for ppar _amp_#x003b3; activation effectively reduced the lps stimulated production of pgj 2 by directly preventing the enzymatic activity of cox 2 rather than its expression as previously described in activated monocytic cell lines [ 80 83 ] and in bv 2 cells [ 75 ].
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox 2	1.0	the reduction of cox 2 enzymatic activity could be achieved through the modifications of key cysteine residues [ 84 ] as suggested by the ability of 15d pgj 2 electrophilic _amp_#x003b1; _amp_#x003b2; unsaturated ketones t
613	APOE	apolipoprotein E	apolipoprotein e	1.0	in a second recent trial the improvement in cognition after 6 months of rosiglitazone treatment was significant only in ad patients who did not have the _amp_#x003b5; 4 allele of the apolipoprotein e [ 92 ] a genotype associate with a higher risk to develop ad.