SciMiner Result Report Page

Document Information

PMID	17350694 ( )
Title	The endocannabinoid system in targeting inflammatory neurodegenerative diseases.
Abstract	The classical divide between degenerative and inflammatory disorders of the CNS is vanishing as accumulating evidence shows that inflammatory processes are important in the pathophysiology of primarily degenerative disorders, and neurodegeneration complicates primarily inflammatory diseases of the brain and spinal cord. Here, we review the contribution of degenerative and inflammatory processes to CNS disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis and HIV-associated dementia. An early combination of neuroprotective and anti-inflammatory approaches to these disorders seems particularly desirable because isolated treatment of one pathological process might worsen another. We also discuss the apparently unique opportunity to modify neurodegeneration and neuroinflammation simultaneously by pharmacological manipulation of the endocannabinoid system in the CNS and in peripheral immune cells. Current knowledge of this system and its involvement in the above CNS disorders are also reviewed. Vergata, Rome 00133, 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
3553	FAAH	fatty acid amide hydrolase	16	FAAH \| fatty acid amide hydrolase \|
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	14	TRPV1 \|
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	10	nape pld \| NAPE-PLD \|
473	AMT	aminomethyltransferase	3	AMT \|
4931	HLA-A	major histocompatibility complex, class I, A	2	MHC \|
4459	GPLD1	glycosylphosphatidylinositol specific phospholipase D1	2	phospholipase d \|
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	2	tumor necrosis factor \|
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	1	protein kinase b \|
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	1	amyloid \|
19986	CYCS	cytochrome c, somatic	1	cytochrome c \|
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	1	nitric oxide synthase \|
5991	IL1A	interleukin 1, alpha	1	interleukin 1 \|
8975	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	1	phosphatidylinositol 3 kinase \|
238	ADCY7	adenylate cyclase 7	1	adenylyl cyclase \|
1165	DAGLA	diacylglycerol lipase, alpha	1	diacylglycerol lipase \|
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	1	SOD1 \|

Targets by SciMiner Full list

HUGO ID	Symbol	Name	ActualStr	Score	FlankingText
4931	HLA-A	major histocompatibility complex, class I, A	MHC	0.6	Since the discovery of MHC class II antigens in the microglia surrounding amyloid plaques and
620	APP	amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)	amyloid	1.0	discovery of MHC class II antigens in the microglia surrounding amyloid plaques and dystrophic neuritis several inflammatory processes have been described
11179	SOD1	superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))	SOD1	0.5	anti-inflammatory agents prolong the survival of transgenic mice expressing human SOD1 with a G93A mutation (hSOD1G93A), hSOD1G93A an animal model of
4931	HLA-A	major histocompatibility complex, class I, A	MHC	0.6	Normally in fact they do not express MHC molecules which is an essential requirement for cell susceptibility to
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	opening of intracellular Ca 2 stores inhibition of AMT and FAAH antioxidative effects
473	AMT	aminomethyltransferase	AMT	0.1	2 channels opening of intracellular Ca 2 stores inhibition of AMT and FAAH antioxidative effects
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	_amp_#x2022 Signaling through TRPV1 receptors
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	characterized ECS elements often includes the type-1 vanilloid receptor (TRPV1), TRPV1 although this receptor does not strictly belong to the ECS
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	In fact TRPV1 has emerged as a key target of the amide N
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	dopamine cell survival by potentiating the toxic effects of the TRPV1 agonist capsaicin 37
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	thus conceivable that endocannabinoids such as AEA which activates both TRPV1 and CB 1 receptors 33 might contribute to PD pathophysiology
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	obtained through genetic ablation of fatty acid amide hydrolase (FAAH) FAAH 38 exert robust anti-inflammatory and neuroprotective effects in hSOD1G93A mice
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	the synthesis of new AEA after the direct activation of TRPV1 by AM404 rather than to AMT inhibition
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	Several studies have provided strong evidence that FAAH owing to its broad distribution might represent an attractive therapeutic
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	For example inhibition of FAAH by URB597 can augment endogenous brain levels of AEA and
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	Similarly AM374 another FAAH inhibitor has been shown to exert potent neuroprotective effects in
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	Furthermore another selective and powerful FAAH inhibitor that has been used for the treatment of pathological
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	on the endocannabinoid tone and thus favors the use of FAAH inhibitors to treat the inflammatory and neurodegenerative damage associated with
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	have distinct pharmacological profiles on CB 1 CB 2 and TRPV1 receptors thus it can be anticipated that differential modulation of
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	with the fact that AEA but not 2-AG binds to TRPV1 33 suggests that agents that can modulate 2-AG levels within
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	By contrast stimulation of TRPV1 favors inflammation 27 as a result modulation of AEA-dependent activation
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	NAPE-PLD	1.3	been for N -acylphosphatidylethanolamine (NAPE)-specific NAPE -specific phospholipase D (NAPE-PLD) NAPE-PLD 59 and FAAH 60 and 61 with respect to AEA
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	-acylphosphatidylethanolamine (NAPE)-specific NAPE -specific phospholipase D (NAPE-PLD) NAPE-PLD 59 and FAAH 60 and 61 with respect to AEA
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	that our hypothesis that a balance between CB receptors and TRPV1 modulates the dual nature of neurological diseases finds a nice
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	in pathological pain sensation where it has been demonstrated that TRPV1 functions to oppose CB-receptor-dependent effects 62
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	AEA seems to be largely dependent on its hydrolysis by FAAH rather than on its synthesis by Ca 2 -dependent N
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	NAPE-PLD	1.3	on its synthesis by Ca 2 -dependent N -acyltransferase or NAPE-PLD
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	NAPE-PLD	1.3	If not therapeutic agents per se inhibitors of NAPE-PLD FAAH AMT DAGL or MAGL could be used together with
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	If not therapeutic agents per se inhibitors of NAPE-PLD FAAH AMT DAGL or MAGL could be used together with AEA
473	AMT	aminomethyltransferase	AMT	0.3	If not therapeutic agents per se inhibitors of NAPE-PLD FAAH AMT DAGL or MAGL could be used together with AEA or
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	The mechanism of action of cannabidiol relies on AMT and FAAH inhibition and on antioxidative properties as a result this natural
473	AMT	aminomethyltransferase	AMT	0.1	The mechanism of action of cannabidiol relies on AMT and FAAH inhibition and on antioxidative properties as a result
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	NAPE-PLD	1.3	NArPE is then cleaved by NAPE-PLD a recently characterized phospholipase D which releases AEA and phosphatidic
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	up by cells AEA is a substrate for the hydrolase FAAH which breaks the amide bond and releases arachidonic acid and
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	Once accumulated in the cell 2-AG can be degraded by FAAH or more efficiently by a specific MAGL
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	TRPV1 is another key molecular target of AEA but importantly not
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	CB 1 or CB 2 receptors and by AEA through TRPV1 are summarized in Box 1 along with the biological actions
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	the ECS are located in the plasma membrane apart from FAAH which is bound to intracellular membranes and MAGL which is
12716	TRPV1	transient receptor potential cation channel, subfamily V, member 1	TRPV1	0.6	one hand AEA might control inflammatory processes by binding to TRPV1 such that drugs that are able to modulate the AEA
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	NAPE-PLD	1.3	drugs that are able to modulate the AEA metabolic enzymes NAPE-PLD and FAAH might be exploited to curb neuroinflammation
3553	FAAH	fatty acid amide hydrolase	FAAH	2.2	are able to modulate the AEA metabolic enzymes NAPE-PLD and FAAH might be exploited to curb neuroinflammation
5991	IL1A	interleukin 1, alpha	interleukin 1	1.0	in addition microglia and macrophages activated by hiv seem to damage neurons through the release of neurotoxins such as arachidonic acid glutamate tumor necrosis factor _amp_#x3b1; and interleukin 1 [25] .
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tumor necrosis factor	1.0	in addition microglia and macrophages activated by hiv seem to damage neurons through the release of neurotoxins such as arachidonic acid glutamate tumor necrosis factor _amp_#x3b1; and interleukin 1 [25] .
7873	NOS2A	nitric oxide synthase 2A (inducible, hepatocytes)	nitric oxide synthase	1.0	ion of voltage gated l n and p/q type ca 2+ channels activation of k + channels activation of focal adhesion kinase activation of cytosolic phospholipase a 2 activation cb 1 r or inhibition cb 2 r of nitric oxide synthase.
238	ADCY7	adenylate cyclase 7	adenylyl cyclase	1.0	inhibition of adenylyl cyclase activation of mitogen activated protein kinase inhibition of voltage gated l n and p/q type ca 2+ channels activation of k + channels activation of focal adhesion kinase activation of cytosolic phosp
19986	CYCS	cytochrome c, somatic	cytochrome c	1.0	activation of non selective ion channels activation of protein kinases opening of intracellular ca 2+ stores dissipation of mitochondrial membrane potential mitochondrial uncoupling cytochrome c release from mitochondria activation of caspases.
8975	PIK3CA	phosphoinositide-3-kinase, catalytic, alpha polypeptide	phosphatidylinositol 3 kinase	1.0	cascades; iii antioxidant activity mainly owing to the phenol group of various resorcinol type cannabinoids; iv suppression of the production of tumor necrosis factor _amp_#x3b1;; v activation of the phosphatidylinositol 3 kinase and protein kinase b pathway; vi induction of phosphorylation of extracellular regulated kinases; and vii induction of the expression of transcription factors and neurotrophins.
391	AKT1	v-akt murine thymoma viral oncogene homolog 1	protein kinase b	1.0	mainly owing to the phenol group of various resorcinol type cannabinoids; iv suppression of the production of tumor necrosis factor _amp_#x3b1;; v activation of the phosphatidylinositol 3 kinase and protein kinase b pathway; vi induction of phosphorylation of extracellular regulated kinases; and vii induction of the expression of transcription factors and neurotrophins.
11892	TNF	tumor necrosis factor (TNF superfamily, member 2)	tumor necrosis factor	1.0	tic level followed by inhibition of subsequent noxious cascades; iii antioxidant activity mainly owing to the phenol group of various resorcinol type cannabinoids; iv suppression of the production of tumor necrosis factor _amp_#x3b1;; v activation of the phosphatidylinositol 3 kinase and protein kinase b pathway; vi induction of phosphorylation of extracellular regulated kinases; and vii induction of the expression of
3553	FAAH	fatty acid amide hydrolase	fatty acid amide hydrolase	1.0	pharmacological agonists of cb receptors and increased levels of endocannabinoids obtained through genetic ablation of fatty acid amide hydrolase faah [38] exert robust anti inflammatory and neuroprotective effects in hsod1g93a mice delaying disease progression 39 and 40 .
1165	DAGLA	diacylglycerol lipase, alpha	diacylglycerol lipase	1.0	by contrast the recent discovery of potent and specific inhibitors of diacylglycerol lipase dagl such as o3841 [53] table 1 suggests that it could become possible to dissect the contribution of 2 arachidonoylglycerol 2 ag and that of aea to neurological disorders.
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	nape pld	1.0	d dagl regulation and the role of these lipases in maintaining the endocannabinoid tone in vivo is of utmost importance as it has been for n acylphosphatidylethanolamine nape specific phospholipase d nape pld [59] and faah 60 and 61 with respect to aea.
4459	GPLD1	glycosylphosphatidylinositol specific phospholipase D1	phospholipase d	1.0	nding of magl and dagl regulation and the role of these lipases in maintaining the endocannabinoid tone in vivo is of utmost importance as it has been for n acylphosphatidylethanolamine nape specific phospholipase d nape pld [59] and faah 60 and 61 with respect to aea.
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	nape pld	1.0	for example control of the cellular activity of aea seems to be largely dependent on its hydrolysis by faah rather than on its synthesis by ca 2+ dependent n acyltransferase or nape pld.
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	nape pld	1.0	if not therapeutic agents per se inhibitors of nape pld faah amt dagl or magl could be used together with aea or 2 ag analogs to lower the doses or to shorten the treatment necessary in vivo to observe an effect and thus to minimize the possible psychotro
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	nape pld	1.0	narpe is then cleaved by nape pld a recently characterized phospholipase d which releases aea and phosphatidic acid.
4459	GPLD1	glycosylphosphatidylinositol specific phospholipase D1	phospholipase d	1.0	narpe is then cleaved by nape pld a recently characterized phospholipase d which releases aea and phosphatidic acid.
21683	NAPEPLD	N-acyl phosphatidylethanolamine phospholipase D	nape pld	1.0	on the one hand aea might control inflammatory processes by binding to trpv1 such that drugs that are able to modulate the aea metabolic enzymes nape pld and faah might be exploited to curb neuroinflammation.