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PMID	17569578 ( )
Title	PPARs in the brain.
Abstract	The biology of peroxisome proliferator activated receptors (PPARs) in physiological and pathophysiological processes has been primarily studied in peripherial organs and tissues. Recently it became clear that PPARs play an important role for the pathogenesis of various disorders of the CNS. The finding that activation of PPARs, and in particular, the PPARgamma isoform, suppresses inflammation in peripherial macrophages and in models of human autoimmune disease, instigated the experimental evaluation of these salutary actions for several CNS disorders that have an inflammatory component. Activation of all PPAR isoforms, but especially of PPARgamma, has been found to be protective in murine in vitro and in vivo models of Multiple Sclerosis. The verification of these findings in human cells prompted the initiation of clinical studies evaluating PPARgamma activation in Multiple Sclerosis patients. Likewise, Alzheimer's disease has a prominent inflammatory component that arises in response to neurodegeneration and to extracellular deposition of beta-amyloid peptides. The fact that non steroidal anti-inflammatory drugs (NSAIDs) delay the onset and reduce the risk to develop Alzheimer's disease, while they also bind to and activate PPARgamma, led to the hypothesis that one dimension of NSAID protection in AD may be mediated by PPARgamma. Several lines of evidence from in vitro and in vivo studies have supported this hypothesis, using Alzheimer disease related transgenic cellular and animal models. The ability of PPAR agonists to elicit anti-amyloidogenic, anti-inflammatory and insulin sensitizing effects may account for the observed effects. A number of clinical trials employing PPAR agonists have yielded promising results and further trials are in preparation, which aim to delineate the exact mechanism of interaction. Animal models of other neurodegenerative diseases such as Parkinson's and Amyotrophic lateral sclerosis, both associated with a considerable degree of CNS inflammation, have been studied with a positive outcome. Yet it is not clear whether reduction of inflammation or additional mechanisms account for the observed neuroprotection. Less is known about the physiological role of PPARs for brain development, maintenance and function. Lesions from transgenic mouse models, however, provide evidence that PPARs may play pivotal roles for CNS development and function. University of Munster, Albert Schweitzer-Strasse 33, 48149 Munster, Germany. heneka@uni-muenster.de

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
9232	PPARA	peroxisome proliferator-activated receptor alpha	52	PPAR \| PPARs \| PPAR-independent \|
7197	MOG	myelin oligodendrocyte glycoprotein	10	MOG \| myelin oligodendrocyte glycoprotein \|
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	9	iNOS \|
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	8	COX2 \| COX-2 \| cox2 \| cox 2 \|
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	7	APP \| amyloid \|
6081	INS	insulin	6	insulin \|
6018	IL6	interleukin 6 (interferon, beta 2)	5	IL-6 \| il 6 \| interleukin 6 \|
6014	IL4	interleukin 4	4	Il-4 \| IL-4 \| il 4 \|
990	BCL2	B-cell CLL/lymphoma 2	3	Bcl-2 \| bcl 2 \|
5381	IDE	insulin-degrading enzyme	3	IDE \| insulin degrading enzyme \|
933	BACE1	beta-site APP-cleaving enzyme 1	3	BACE1 \|
10637	CXCL10	chemokine (C-X-C motif) ligand 10	2	ip 10 \| IP-10 \|
10618	CCL2	chemokine (C-C motif) ligand 2	2	MCP1 \| mcp1 \|
10638	CXCL11	chemokine (C-X-C motif) ligand 11	2	i tac \| I-TAC \|
11782	TH	tyrosine hydroxylase	2	tyrosine hydroxylase \|
6207	JUP	junction plakoglobin	2	catenin \|
7107	MKI67	antigen identified by monoclonal antibody Ki-67	2	ki 67 \| Ki-67 \|
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	2	ap 1 \| AP-1 \|
7176	MMP9	matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)	2	mmp9 \| MMP9 \|
6001	IL2	interleukin 2	2	il 2 \| IL-2 \|
5962	IL10	interleukin 10	2	IL-10 \| il 10 \|
11925	TNFSF10	tumor necrosis factor (ligand) superfamily, member 10	2	TRAIL-induced \|
7166	MMP2	matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)	2	matrix metalloproteinase 2 \| MMP2 \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	2	SOD1 \|
26101	ACSF2	acyl-CoA synthetase family member 2	1	acyl coa synthetase 2 \|
19383	SOCS1	suppressor of cytokine signaling 1	1	suppressor of cytokine signaling 1 \|
12518	UCP2	uncoupling protein 2 (mitochondrial, proton carrier)	1	uncoupling protein 2 \|
11362	STAT1	signal transducer and activator of transcription 1, 91kDa	1	STATs \|
7098	CXCL9	chemokine (C-X-C motif) ligand 9	1	MIG \|
10417	RPS27A	ribosomal protein S27a	1	ubiquitin \|
7672	NCOR1	nuclear receptor co-repressor 1	1	n cor \|
13716	C4orf6	chromosome 4 open reading frame 6	1	expressed in neuroblastoma \|
593	BIRC5	baculoviral IAP repeat-containing 5 (survivin)	1	survivin \|
6925	MBP	myelin basic protein	1	MBP \|
4604	CXCL3	chemokine (C-X-C motif) ligand 3	1	CXCL3 \|
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	1	FLIP \|
613	APOE	apolipoprotein E	1	ApoE \|
10632	CCL5	chemokine (C-C motif) ligand 5	1	RANTES \|
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	1	tumor necrosis factor \|
1678	CD4	CD4 molecule	1	CD4 \|
10739	SEMA6B	sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B	1	semaphorin 6b \|
14065	HDAC9	histone deacetylase 9	1	HDAC \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	The biology of peroxisome proliferator activated receptors (PPARs) PPARs in physiological and pathophysiological processes has been primarily studied in
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Recently it became clear that PPARs play an important role for the pathogenesis of various disorders
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	The finding that activation of PPARs and in particular the PPAR_amp_#x3b3 isoform suppresses inflammation in peripherial
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	Activation of all PPAR isoforms but especially of PPAR_amp_#x3b3 has been found to be
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.0	in response to neurodegeneration and to extracellular deposition of _amp_#x3b2 -amyloid peptides
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	The ability of PPAR agonists to elicit anti-amyloidogenic anti-inflammatory and insulin sensitizing effects may
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	A number of clinical trials employing PPAR agonists have yielded promising results and further trials are in
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Less is known about the physiological role of PPARs for brain development maintenance and function
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Lesions from transgenic mouse models however provide evidence that PPARs may play pivotal roles for CNS development and function
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Physiological function of PPARs in the brain
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	The peroxisome proliferator activated receptors (PPARs) PPARs are ligand-inducible transcription factors which belong to the superfamily of
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	and retinoid receptors it is thought that the ability of PPARs to bind to a ligand was acquired during metazoan evolution
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	Three different PPAR isotypes (PPAR_amp_#x3b1;, PPAR_amp_#x3b1 PPAR_amp_#x3b2 also called _amp_#x3b4 and PPAR_amp_#x3b3 have
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	PPARs are involved in several aspects of tissue differentiation and rodent
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	PPAR_amp_#x3b1 _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 and _amp_#x3b3 developed from a common PPAR gene with broad ligand-binding specificity itself derived from the ancestral
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	PPARs regulate gene expression through multiple mechanisms and function as obligate
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Like the other members of the superfamily PPARs are composed of four domains
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	E/F E F domain is responsible for the dimerization of PPARs with RXRs and the ligand-dependent transactivation function of the receptor
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	PPARs act to stimulate gene expression through binding to conserved DNA
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	PPARs also act to inhibit proinflammatory gene expression and do so
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	The PPARs act principally as lipid sensors and regulate whole body metabolism
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Binding of PPARs to their specific ligands is leading to conformational changes which
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Even though all PPARs can be attributed to a common ancestral nuclear receptor each
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	can be attributed to a common ancestral nuclear receptor each PPAR isotype has its own properties with regard to ligand binding
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	All three PPAR isotypes can be activated by polyunsaturated fatty acids with different
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	There is less known about the expression of the PPARs during human development 6 122 and 126
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	All three PPAR isotypes are co-expressed in the nervous system during late rat
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	The expression of the three PPAR isotypes peaks in the rat CNS between day 13.5 and
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	is isotype specific and regulated during development suggests that the PPARs may play a role during the formation of the CNS
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	All PPARs including PPAR_amp_#x3b3 have been described in the adult and developing
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	Furthermore it has been suggested that PPAR activation in neurons may directly influence neuron cell viability and
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	The localization of PPARs has also been investigated in purified cultures of neural cells
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	Astrocytes possess all three PPAR isotypes although to different degrees depending on the brain area
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	The role of PPARs in the CNS is mainly been related to lipid metabolism
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Role of PPARs in neuro-immunological disease
6018	IL6	interleukin 6 (interferon, beta 2)	IL-6	1.9	TNF_amp_#x3b1 interferon _amp_#x3b3;_amp_#xa0;(IFN_amp_#x3b3;), _amp_#x3b3 _amp_#xa0 IFN_amp_#x3b3 and interleukin 6 (IL-6) IL-6 are regularly found in multiple sclerosis brain lesions and in
7197	MOG	myelin oligodendrocyte glycoprotein	MOG	1.9	demonstrated in the myelin oligodendrocyte glycoprotein peptide 35_amp_#x2013 55 (MOG MOG 35_amp_#x2013 55 induced EAE model that activation of PPAR_amp_#x3b3 limits
5962	IL10	interleukin 10	IL-10	1.3	PPAR_amp_#x3b3 ligand 15d-PGJ 2 inhibited T-cell proliferation and suppressed IFN_amp_#x3b3 IL-10 and IL-4 generation by activated lymphocytes 53
6014	IL4	interleukin 4	IL-4	1.3	15d-PGJ 2 inhibited T-cell proliferation and suppressed IFN_amp_#x3b3 IL-10 and IL-4 generation by activated lymphocytes 53
7197	MOG	myelin oligodendrocyte glycoprotein	MOG	1.9	then the first to show that oral pioglitzone treatment of MOG 35_amp_#x2013 55 -immunized mice not only reduced brain inflammation and
7197	MOG	myelin oligodendrocyte glycoprotein	MOG	1.9	as pioglitazone or GW7845 within the first two weeks of MOG 35_amp_#x2013 55 -induced EAE a phenomenon that may be explained
7197	MOG	myelin oligodendrocyte glycoprotein	MOG	1.9	suppressed the IFN_amp_#x3b3 secretion of splenic T cells stimulated by MOG 35_amp_#x2013 55 in vitro 61
10618	CCL2	chemokine (C-C motif) ligand 2	MCP1	1.3	been shown to reduce the expression of the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117
10637	CXCL10	chemokine (C-X-C motif) ligand 10	IP-10	1.3	to reduce the expression of the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117
4604	CXCL3	chemokine (C-X-C motif) ligand 3	CXCL3	0.3	the expression of the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117
7098	CXCL9	chemokine (C-X-C motif) ligand 9	MIG	0.3	expression of the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117
10638	CXCL11	chemokine (C-X-C motif) ligand 11	I-TAC	1.3	the monocytic chemoattractant MCP1 95 IP-10 (CXCL3), CXCL3 MIG and I-TAC 117
10632	CCL5	chemokine (C-C motif) ligand 5	RANTES	1.3	pioglitazone a decrease in the mRNA levels for MIP1_amp_#x3b1 and RANTES both key chemokines in the MOG 35_amp_#x2013 55 induced EAE
7197	MOG	myelin oligodendrocyte glycoprotein	MOG	1.9	levels for MIP1_amp_#x3b1 and RANTES both key chemokines in the MOG 35_amp_#x2013 55 induced EAE model has been observed 61
7197	MOG	myelin oligodendrocyte glycoprotein	MOG	1.9	an increase in T cell proliferation and Th1 response upon MOG peptide stimulation when compared to PPAR_amp_#x3b3 wild type littermate controls
7197	MOG	myelin oligodendrocyte glycoprotein	MOG	1.9	PPAR_amp_#x3b2;/_amp_#x3b4; PPAR_amp_#x3b2 _amp_#x3b4 agonist GW0742 exerted beneficial effects in the MOG 35_amp_#x2013 55 induced EAE model 136
6001	IL2	interleukin 2	IL-2	1.3	by T lymphocytes and its activation results in suppression of IL-2 production and proliferation 44 and 116
7197	MOG	myelin oligodendrocyte glycoprotein	MOG	1.9	PPAR_amp_#x3b1 agonist reduced the IgG response in mice immunized with MOG 35_amp_#x2013 55 and complete Freund_amp_#x2019 s adjuvant 43
6018	IL6	interleukin 6 (interferon, beta 2)	IL-6	1.9	treated mice showed an impaired generation of IFN_amp_#x3b3 TNF_amp_#x3b1 and IL-6 in response to MOG peptide in vitro restimulation
7197	MOG	myelin oligodendrocyte glycoprotein	MOG	1.9	impaired generation of IFN_amp_#x3b3 TNF_amp_#x3b1 and IL-6 in response to MOG peptide in vitro restimulation
6014	IL4	interleukin 4	Il-4	1.3	The authors showed that gemfibrozil and ciprofibrate induced Il-4 production in murine and human lymphocytes while IFN_amp_#x3b3 production was
6925	MBP	myelin basic protein	MBP	0.3	In addition oral treatment of mice with gemfibrozil protected from MBP induced EAE and strongly reduced CD4 lymphocyte and macrophage infiltration
1678	CD4	CD4 molecule	CD4	0.6	with gemfibrozil protected from MBP induced EAE and strongly reduced CD4 lymphocyte and macrophage infiltration into the CNS
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	The aforementioned in vitro and in vivo experiments suggest that PPAR activation may be used as a new therapeutic avenue in
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Role of PPARs in neurodegenerative disorders
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	1.0	In addition neuronal expression of inflammatory enzyme systems including iNOS have been described in AD 77 105 and 165
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	1.0	The experimental expression of iNOS in neurons resulted in time dependent neuronal cell death which
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	1.0	PPAR_amp_#x3b3 activation in microglial cells suppressed inflammatory cytokine expression iNOS expression and NO production and inhibition of COX2 and subsequent
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX2	2.5	cytokine expression iNOS expression and NO production and inhibition of COX2 and subsequent generation of immunostimulated prostanoid synthesis 38
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	AP-1	1.3	transcription factor NF_amp_#x3ba B (and and to a lesser extent AP-1 and STATs 46
11362	STAT1	signal transducer and activator of transcription 1, 91kDa	STATs	0.3	NF_amp_#x3ba B (and and to a lesser extent AP-1 and STATs 46
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	APP	0.3	been investigated in animal models of AD that overexpress human APP
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.0	The finding that PPAR_amp_#x3b3 agonists elicited a reduction in amyloid pathology in animal models of the disease may be the
933	BACE1	beta-site APP-cleaving enzyme 1	BACE1	0.5	was the result of inhibition of beta secretease 1 (BACE1) BACE1 expression through a PPAR_amp_#x3b3 -dependent suppression of the BACE1 gene
933	BACE1	beta-site APP-cleaving enzyme 1	BACE1	0.5	(BACE1) BACE1 expression through a PPAR_amp_#x3b3 -dependent suppression of the BACE1 gene promoter 149 and 150
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	APP	0.3	Similarly Heneka et al found that oral pioglitazone treatment of APP transgenic mice reduced BACE1 transcription and expression
933	BACE1	beta-site APP-cleaving enzyme 1	BACE1	0.5	found that oral pioglitazone treatment of APP transgenic mice reduced BACE1 transcription and expression
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	APP	0.3	of independent studies found that PPAR_amp_#x3b3 activation regulated both cellular APP levels and A_amp_#x3b2 production by stimulating the ubiquitin-mediated degradation of
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	APP	0.3	levels and A_amp_#x3b2 production by stimulating the ubiquitin-mediated degradation of APP 45
5381	IDE	insulin-degrading enzyme	IDE	1.3	an increase in the levels of insulin degrading enzyme (IDE) IDE in rosiglitazone treated transgenic mice
5381	IDE	insulin-degrading enzyme	IDE	1.3	IDE acts to proteolytically degrade amyloid peptides and has been genetically
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.0	IDE acts to proteolytically degrade amyloid peptides and has been genetically linked to AD 139
613	APOE	apolipoprotein E	ApoE	0.0	the differential effects of rosiglitazone in individuals depending on their ApoE genotype is unexplained
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	1.0	studies suggested that neuroinflammatory changes accompanied by microglial and astroglial iNOS expression may play a pivotal role in PD 79 and
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	1.0	Since PPAR_amp_#x3b3 activation results in a profound suppression of iNOS in peripheral macrophages 37 and 142 as well as in
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	1.0	In part iNOS suppression in MPTP treated mice may have been achieved by
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX-2	2.8	pioglitazone treated SOD1-G93A mice as were the protein levels of COX-2 and iNOS
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	1.0	SOD1-G93A mice as were the protein levels of COX-2 and iNOS
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	0.5	whereas both the mRNA and protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected 154
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	0.5	protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected 154
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	PPARs in cerebral ischemia
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	1.0	chemokine expression as well as elevated expression of adhesion molecules iNOS COX2 and other inflammatory mediators which act to exacerbate the
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX2	2.5	expression as well as elevated expression of adhesion molecules iNOS COX2 and other inflammatory mediators which act to exacerbate the tissue
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	iNOS	1.0	infiltration of peripheral leukocytes diminished microglial activation and reduction of iNOS COX2 and cytokine expression
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	COX2	2.5	of peripheral leukocytes diminished microglial activation and reduction of iNOS COX2 and cytokine expression
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	The principal focus of studies of PPAR agonists has been on agonists of the PPAR_amp_#x3b3 isoform however
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	Likewise Arsenijevic and colleagues have explored the role of PPAR _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 in murine stroke and found that PPAR
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	PPAR _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 in murine stroke and found that PPAR _amp_#x3b2;/_amp_#x3b4; _amp_#x3b2 _amp_#x3b4 null mice exhibited significantly greater infarct sizes
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	risk for ischemic stroke 103 further supporting the importance of PPARs in cerebral ischemia
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	PPARs and tumors of the nervous system
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	All isoforms of PPARs are expressed in the brain 133 and 142 as well
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	in other neoplastic disease several natural and synthetic ligands of PPARs have been tested for their efficacy in the treatment of
7166	MMP2	matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)	MMP2	0.3	was associated with a decrease in matrix metalloproteinase 2 (MMP2) MMP2 levels
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	Tetradecylthioacetic acid (TTA), TTA a saturated fatty acid and PPAR ligand inhibited growth of BT4Cn rat glioma cells at increased
7107	MKI67	antigen identified by monoclonal antibody Ki-67	Ki-67	1.6	proliferation in rat glioma cells was inhibited as measured by Ki-67 expression
7176	MMP9	matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)	MMP9	0.3	decreased tumor invasion in vivo that were correlated with reduced MMP9 levels
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	PPAR agonists have also been shown to exhibit effects on tumor
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR-independent	2.5	also been shown to exhibit effects on tumor biology through PPAR-independent mechanisms
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR-independent	2.5	growth of T98G human glioblastoma cells and induced apoptosis through PPAR-independent mechanisms since their respective antagonists MK-886 and GW9662 did not
11925	TNFSF10	tumor necrosis factor (ligand) superfamily, member 10	TRAIL-induced	2.2	The TZD troglitazone sensitized human glioma cells to TRAIL-induced apoptosis in a process independent of PPAR_amp_#x3b3 2 and 152
1876	CFLAR	CASP8 and FADD-like apoptosis regulator	FLIP	1.8	treatment led to a marked down-regulation of the anti-apoptotic proteins FLIP and survivin 152 as well Bcl-2 2 and so could
990	BCL2	B-cell CLL/lymphoma 2	Bcl-2	1.0	of the anti-apoptotic proteins FLIP and survivin 152 as well Bcl-2 2 and so could possibly counteract the capability of tumor
11925	TNFSF10	tumor necrosis factor (ligand) superfamily, member 10	TRAIL	2.2	Hence a combination therapy of troglitazone and TRAIL might be a promising experimental approach
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPAR	3.0	The molecular understanding of antineoplastic mechanisms of PPAR agonists is still emerging
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	by a number of reports dealing with the influence of PPARs on glioma treatment in vitro
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	However the agonists of PPARs in particular the TZDs seem to be promising candidates for
9232	PPARA	peroxisome proliferator-activated receptor alpha	PPARs	2.8	Therefore most studies that assess the influence of PPARs on treatment of neuroblastoma evaluate the impact of its natural
14065	HDAC9	histone deacetylase 9	HDAC	1.9	interaction with retinoblastoma protein (Rb) Rb and histone deacetylase (HDAC) HDAC 56
6081	INS	insulin	insulin	1.0	the ability of ppar agonists to elicit anti amyloidogenic anti inflammatory and insulin sensitizing effects may account for the observed effects.
7672	NCOR1	nuclear receptor co-repressor 1	n cor	1.0	nf_amp_#x3ba;b regulated inflammatory genes are maintained in a repressed state through their association with n cor containing corepressor complexes.
26101	ACSF2	acyl-CoA synthetase family member 2	acyl coa synthetase 2	1.0	acyl coa synthetase 2 which is crucial in fatty acid utilization is regulated by ppar_amp_#x3b2;/_amp_#x3b4; at the transcriptional level providing a facile measure of ppar_amp_#x3b2;/_amp_#x3b4; action.
6018	IL6	interleukin 6 (interferon, beta 2)	interleukin 6	1.0	several cytokines including tumor necrosis factor _amp_#x3b1;_amp_#xa0; tnf_amp_#x3b1; interferon _amp_#x3b3;_amp_#xa0; ifn_amp_#x3b3; and interleukin 6 il 6 are regularly found in multiple sclerosis brain lesions and in spinal cord infiltrates of eae mice [124] .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tumor necrosis factor	1.0	several cytokines including tumor necrosis factor _amp_#x3b1;_amp_#xa0; tnf_amp_#x3b1; interferon _amp_#x3b3;_amp_#xa0; ifn_amp_#x3b3; and interleukin 6 il 6 are regularly found in multiple sclerosis brain lesions and in spinal cord infiltrates of e
6018	IL6	interleukin 6 (interferon, beta 2)	il 6	1.0	several cytokines including tumor necrosis factor _amp_#x3b1;_amp_#xa0; tnf_amp_#x3b1; interferon _amp_#x3b3;_amp_#xa0; ifn_amp_#x3b3; and interleukin 6 il 6 are regularly found in multiple sclerosis brain lesions and in spinal cord infiltrates of eae mice [124] .
7197	MOG	myelin oligodendrocyte glycoprotein	myelin oligodendrocyte glycoprotein	1.0	using the synthetic ppar_amp_#x3b3; ligand troglitazone niino et al. first demonstrated in the myelin oligodendrocyte glycoprotein peptide 35_amp_#x2013;55 mog 35_amp_#x2013;55 induced eae model that activation of ppar_amp_#x3b3; limits the development of clinical symptoms and infiltration of brain parenchyma by peripherial leuk
5962	IL10	interleukin 10	il 10	1.0	c implication of this finding was further supported by a study of diab et al. showing that the endogenous ppar_amp_#x3b3; ligand 15d pgj 2 inhibited t cell proliferation and suppressed ifn_amp_#x3b3; il 10 and il 4 generation by activated lymphocytes [53] .
6014	IL4	interleukin 4	il 4	1.0	ion of this finding was further supported by a study of diab et al. showing that the endogenous ppar_amp_#x3b3; ligand 15d pgj 2 inhibited t cell proliferation and suppressed ifn_amp_#x3b3; il 10 and il 4 generation by activated lymphocytes [53] .
10637	CXCL10	chemokine (C-X-C motif) ligand 10	ip 10	1.0	ppar_amp_#x3b3; agonists have been shown to reduce the expression of the monocytic chemoattractant mcp1 [95] ip 10 cxcl3 mig and i tac [117] .
10618	CCL2	chemokine (C-C motif) ligand 2	mcp1	1.0	ppar_amp_#x3b3; agonists have been shown to reduce the expression of the monocytic chemoattractant mcp1 [95] ip 10 cxcl3 mig and i tac [117] .
10638	CXCL11	chemokine (C-X-C motif) ligand 11	i tac	1.0	ppar_amp_#x3b3; agonists have been shown to reduce the expression of the monocytic chemoattractant mcp1 [95] ip 10 cxcl3 mig and i tac [117] .
6001	IL2	interleukin 2	il 2	1.0	importantly ppar_amp_#x3b1; is expressed by t lymphocytes and its activation results in suppression of il 2 production and proliferation [44] and [116] .
6018	IL6	interleukin 6 (interferon, beta 2)	il 6	1.0	in the same study splenocytes derived from wy14 643 treated mice showed an impaired generation of ifn_amp_#x3b3; tnf_amp_#x3b1; and il 6 in response to mog peptide in vitro restimulation.
6014	IL4	interleukin 4	il 4	1.0	the authors showed that gemfibrozil and ciprofibrate induced il 4 production in murine and human lymphocytes while ifn_amp_#x3b3; production was decreased.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	electron microscopy and western blot analysis revealed dna condensation and down regulation of bcl 2 suggesting the induction of apoptosis in activated t lymphocytes [151] .
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox2	1.0	ppar_amp_#x3b3; activation in microglial cells suppressed inflammatory cytokine expression inos expression and no production and inhibition of cox2 and subsequent generation of immunostimulated prostanoid synthesis [38] .
3796	FOS	v-fos FBJ murine osteosarcoma viral oncogene homolog	ap 1	1.0	s are a result of the ability of ppar_amp_#x3b3; to suppress the promoters of proinflammatory genes through antagonism of the actions of the transcription factor nf_amp_#x3ba;b and to a lesser extent ap 1 and stats [46] .
10417	RPS27A	ribosomal protein S27a	ubiquitin	1.0	a series of independent studies found that ppar_amp_#x3b3; activation regulated both cellular app levels and a_amp_#x3b2; production by stimulating the ubiquitin mediated degradation of app [45] .
6207	JUP	junction plakoglobin	catenin	1.0	in addition to the aforementioned mechanisms modulation of the wnt/_amp_#x3b2; catenin signaling pathway may also account for some ppar_amp_#x3b3; mediated beneficial effects in ad since recent findings show that ppar_amp_#x3b3; mediated protection of hippocampal neurons against a_amp_
6207	JUP	junction plakoglobin	catenin	1.0	effects in ad since recent findings show that ppar_amp_#x3b3; mediated protection of hippocampal neurons against a_amp_#x3b2; induced toxicity directly correlates with the modification of _amp_#x3b2; catenin levels inhibition of gsk 3_amp_#x3b2; activity and increased levels of wnt target genes [63] and [83] .
6081	INS	insulin	insulin	1.0	the reduced a_amp_#x3b2; 1_amp_#x2013;42 was argued to arise from an increase in the levels of insulin degrading enzyme ide in rosiglitazone treated transgenic mice.
5381	IDE	insulin-degrading enzyme	insulin degrading enzyme	1.0	the reduced a_amp_#x3b2; 1_amp_#x2013;42 was argued to arise from an increase in the levels of insulin degrading enzyme ide in rosiglitazone treated transgenic mice.
6081	INS	insulin	insulin	1.0	these data were interpreted as evidence for a significant role for peripheral insulin sensitivity in cognition.
6081	INS	insulin	insulin	1.0	ad risk and memory impairment is associated with hyperinsulinemia and insulin resistance features which characterize type ii diabetes [110] and [170] .
6081	INS	insulin	insulin	1.0	these linkages led to the initiation of clinical investigations of insulin sensitizing tzds currently in clinical use for the treatment of type ii diabetes.
11782	TH	tyrosine hydroxylase	tyrosine hydroxylase	1.0	in this study pioglitazone also protected tyrosine hydroxylase positive substantia nigra neurons from mptp induced cell death.
11782	TH	tyrosine hydroxylase	tyrosine hydroxylase	1.0	in addition to the observed effects with ppar_amp_#x3b3; agonists in the mptp model ppar_amp_#x3b1; has been demonstrated in tyrosine hydroxylase th positive cells of the snpc and preventive treatment of mice with the ppar_amp_#x3b1; agonist fenofibrate protected from mptp induced loss of th positive neurons in the snpc and th immunoreactivity
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox 2	1.0	activated microglia were significantly reduced at sites of neurodegeneration in pioglitazone treated sod1 g93a mice as were the protein levels of cox 2 and inos.
19383	SOCS1	suppressor of cytokine signaling 1	suppressor of cytokine signaling 1	1.0	interestingly mrna levels of the suppressor of cytokine signaling 1 and 3 genes were increased by pioglitazone whereas both the mrna and protein levels of endogenous mouse sod1 and of transgenic human sod1 remained unaffected [154] .
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox2	1.0	the peripheral leukocytes and microglia mount a robust inflammatory response with the induction of cytokine and chemokine expression as well as elevated expression of adhesion molecules inos cox2 and other inflammatory mediators which act to exacerbate the tissue damage [9] [12] and [181] .
9605	PTGS2	prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)	cox2	1.0	the salutary actions of the drugs were associated with reduced infiltration of peripheral leukocytes diminished microglial activation and reduction of inos cox2 and cytokine expression.
12518	UCP2	uncoupling protein 2 (mitochondrial, proton carrier)	uncoupling protein 2	1.0	additional mechanisms include the regulation of uncoupling protein 2 a subsequent decrease of lipid peroxidation and improved neuronal survival [30] .
6081	INS	insulin	insulin	1.0	an nih sponsored trial is currently testing the ability of pioglitazone to decrease stroke incidence in non diabetic patients with insulin resistance.
10739	SEMA6B	sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6B	semaphorin 6b	1.0	these ligands strongly downregulated the expression of semaphorin 6b a member of the semaphorin family of axon guidance molecules [34] suggesting suppression of glioma invasion mechanisms by these ppar_amp_#x3b1; agonists.
7166	MMP2	matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)	matrix metalloproteinase 2	1.0	furthermore ppar_amp_#x3b3; agonist ligands increased cell adhesion cell migration and tumor invasion that was associated with a decrease in matrix metalloproteinase 2 mmp2 levels.
7107	MKI67	antigen identified by monoclonal antibody Ki-67	ki 67	1.0	furthermore proliferation in rat glioma cells was inhibited as measured by ki 67 expression.
7176	MMP9	matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)	mmp9	1.0	the authors also observed decreased tumor invasion in vivo that were correlated with reduced mmp9 levels.
593	BIRC5	baculoviral IAP repeat-containing 5 (survivin)	survivin	1.0	troglitazone treatment led to a marked down regulation of the anti apoptotic proteins flip and survivin [152] as well bcl 2 [2] and so could possibly counteract the capability of tumor cells to become resistant to apoptosis.
990	BCL2	B-cell CLL/lymphoma 2	bcl 2	1.0	troglitazone treatment led to a marked down regulation of the anti apoptotic proteins flip and survivin [152] as well bcl 2 [2] and so could possibly counteract the capability of tumor cells to become resistant to apoptosis.
13716	C4orf6	chromosome 4 open reading frame 6	expressed in neuroblastoma	1.0	regardless of the phenotype ppar_amp_#x3b3; is expressed in neuroblastoma cell lines [155] as well as in primary neuroblastoma cells [67] .