LPS (LBP-TLR4-MD2- BPi) Glutathione -- sRAGE RAGE enRAGE - GPx - Alagebrium
randall
We psor heads know that one of the banes of psoriasis is LPS..
If you've been in this group you couldn't have missed it.
Just the other day i posted a thread: Mostly about glutathione & Psor
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/887eabbdbdc40a6e
[There are 17 hits for LPS and 62 hits for glutathione in one post :]
SO?
WELL... what about RAGE (receptor for advanced glycation end products)
and psor heads?
Can you find the LPS and glutathione with RAGE?
It's EASY...but leave your rage out or you won't find it...<W>
When JRSTERN posted the GOOD ARTICLE link from Xoma back in 2001 or
so, some of us (me) went APE stuff...
Let's recap... lps re craP redux:
I'LL go back awhile with the basics for LPS.
(keywords: LPS Bpi LBP psoriasis:) (12 hits on groups mostly ours:)
http://groups.google.com/groups/search?hl=en&qt_s=1&q=bpi+lps+lbp+psoriasis
And this search brings up the GPx mimetic SYI-2074 from Synvista.
GPx is glutathione peroxidase and we've had how many posts to this
group
for Gpx?
ONLY 62 hits for keyword: GPx
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=gpx
And how many for :: glutathione peroxidase:
Over 717 for keyword glutathione on our group:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=glutathione+&qt_g=Search+this+group
OK, so we can see how synvista went under the radar:
http://www.google.com/search?hl=en&q=SYI-2074+glutathione+&btnG=Search&aq=f&oq=&aqi=
http://www.google.com/search?hl=en&q=SYI-2074+glutathione+peroxidase+oral&aq=f&oq=&aqi=
ALT-711 glutathione psoriasis alagebrium chloride
http://www.google.com/search?hl=en&q=ALT-711+glutathione+psoriasis+alagebrium+chloride&btnG=Search&aq=f&oq=&aqi=
So how did we MISS this in combo with LPS?
2,690 hits in our group for LPS:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?hl=en&group=alt.support.skin-diseases.psoriasis&q=lps
WE had this article in the group already?
No... must have missed it. Was December 16, 2008
http://www.medicalnewstoday.com/articles/133132.php
Synvista Therapeutics Announces First Dosing Of SYI-2074 In Clinical
Trial For Psoriasis
Synvista Therapeutics, Inc. (NYSE Alternext US: SYI) has dosed the
first patient in a 30-patient Phase 2 clinical trial of its
proprietary topical GPx-mimetic, SYI-2074, in patients with psoriasis.
The trial is planned to be a 28-day multi-center, randomized, double-
blind, placebo controlled study to assess the efficacy of topical
SYI-2074, applied twice daily, for the treatment of chronic, mild-to-
moderate plaque psoriasis in adults. The trial is being conducted in
three centers in Israel.
"We are very excited to begin phase 2 clinical trials on SYI-2074 for
psoriasis," said Noah Berkowitz, M.D., Ph.D., President and Chief
Executive Officer of Synvista Therapeutics. "We believe that there is
immense potential to expand the scope of treatment modalities for
psoriasis following this trial and look forward to reporting results
in the first quarter of 2009."
About SYI-2074
Synvista's GPx mimetic program is based on the rational design of oral
and topical drugs that mimic the activity of glutathione peroxidase
(GPx), the only enzyme in the human body that reduces oxidized lipids.
GPx is a well validated target for drug development. Animal models
have shown that elevated activity of GPx protects animals from
experiencing heart attacks and atherosclerosis and reduced levels of
GPx put them at risk for those diseases or complications. In humans,
research suggests the risk of cardiovascular disease varies inversely
with levels of GPx activity (i.e., higher levels of oxidized lipids
promote the creation of oxygen free radicals and reactive oxygen
species (ROS), such as H2O2, which can promote inflammation).
As noted above, a topical form of our GPx mimetic SYI-2074 is being
developed for treatment of mild to moderate plaque psoriasis, an
inflammatory disease highly correlated with a molecular signaling
pathway that can be inhibited by SYI-2074.
<sniP>
---------------
ALT-711 glutathione psoriasis alagebrium chloride advanced glycation
(63 hits -- web)
http://www.google.com/search?hl=en&q=ALT-711+glutathione+psoriasis+alagebrium+chloride+advanced+glycation&aq=f&oq=&aqi=
Synvista:
Synvista Therapeutics Announces Progress In Phase 2 Clinical Trial
Program For Alagebrium
http://www.medicalnewstoday.com/articles/135137.php
Article Date: 13 Jan 2009
Synvista Therapeutics Announces Progress In Phase 2 Clinical Trial
Program For Alagebrium
Synvista Therapeutics, Inc. (NYSE Alternext US: SYI) has completed
enrollment of its BENEFICIAL study, a Phase 2 double-blind, placebo-
controlled, randomized trial of the Company's compound alagebrium. The
study is designed to measure the effect of alagebrium on exercise
tolerance in patients with chronic systolic heart failure. In
addition, the Company anticipates completing enrollment of its BREAK
(Beginning a Randomized Evaluation of the A.G.E. [Advanced Glycation
End Product] Breaker Alagebrium in Diastolic Heart Failure) study in
the First Quarter of 2009. BREAK, a randomized, double-blind, placebo
controlled study, evaluates whether alagebrium (200mg twice daily) can
improve exercise tolerance, as measured by the 6-minute walk test, in
patients diagnosed with diastolic heart failure.
"We are extremely pleased with the progress thus far in our clinical
program for alagebrium," said Noah Berkowitz, M.D., Ph.D., President
and Chief Executive Officer of Synvista Therapeutics, developer of
alagebrium. "Based on our dialogue with the FDA, we believe that
exercise tolerance is an approvable regulatory endpoint, in patients
with systolic or diastolic heart failure. Accordingly, we look forward
to the timely completion of these studies which could provide proof of
efficacy and a partial basis for drug approval."
About Alagebrium
Alagebrium is Synvista's clinical candidate for interfering with
A.G.E.-related sclerosis and fibrosis of the heart, kidney and other
tissues leading to heart failure, diabetic nephropathy and other
disorders. It is a proprietary A.G.E. crosslink breaker that is
designed to function unlike any previously developed pharmaceutical
agents to reverse the disease states associated with age or diabetes-
related stiffening of vessels, tissues and organs. Alagebrium has
completed a series of single- and multiple-dose Phase 1 studies in
humans and has demonstrated efficacy in heart failure in several open-
label Phase 2 trials. To date approximately 1,000 patients have
received alagebrium treatment and the drug continues to exhibit a
clean safety profile.
About Heart Failure
Heart failure is a complex clinical syndrome that can result from any
structural or functional cardiac disorder that impairs the ability of
the ventricle to fill with or eject blood. The primary manifestations
of heart failure are dyspnea and fatigue, which may limit exercise
tolerance, result in fluid retention, and lead to pulmonary congestion
and peripheral edema. These abnormalities impair the functional
capacity and quality of life of affected individuals.
Heart failure is a major and growing global public health problem.
Approximately 5 million patients in the U.S. and about 10 million in
Europe have heart failure, according to the American Heart
Association. The number of heart failure deaths has increased steadily
despite advances in treatment. Heart failure results in more than 1
million hospitalizations at a cost of more than $15 billion annually
in the U.S. alone.
Most of the available treatments for heart failure are not aimed at
the underlying pathophysiological processes that occur in the heart
itself. In this respect, the Company believes that accumulation of
A.G.E.s might prove to be a promising, novel target for the treatment
of heart failure. A.G.E.s are proteins formed by oxidative or non-
oxidative reactions. A.G.E.s cause the formation of collagen cross-
links, which result in increased myocardial stiffness whereby the
stiff ventricle fails to relax adequately between beats and to allow
blood to fill the chamber. As a result, blood backs up into the lungs
and makes patients short of breath. More than 50% of patients with
symptoms of heart failure have evidence of a stiff non-compliant
ventricle (heart chamber) by echocardiogram.
=====================
http://www.muni.cz/research/publications/403594/
Gene polymorphisms (G82S,1704G/T, 2184A/G and 2245G/A) in the receptor
of advanced glycation end products (RAGE) with plaque psoriasis
Vladimír Vašků, Kateřina Kaňková, Anna Vašků, Jan Mužík, Lydie
Izakovičová Hollá, Věra Semrádová, Jiří Vácha
Edition: Archives of Dermatological Research, Německo, Springer Verlag
(DEU). ISSN 0340-3696.
Volume 294, number 2, pp. 127-130. 2002
Having in mind relations between oxidative stress, psoriasis and
common disorders, associations of polymorphisms in gene coding for
RAGE with plaque psoriasis considering personal history of diabetes
mellitus, cardiovascular disorders, cancer and allergy were
investigated.Allele frequencies and genotype combinations of the four
polymorphisms in RAGE gene (6p 21.3, G82S, 1704G/T, 2184A/G and 2245A/
G) were compared in a case-control study comprising 272 subjects (130
patients with plaque psoriasis and 142 healthy control subjects of
comparable age and sex distribution). Polymerase chain reaction with
subsequent restriction analysis were used for detection of allele
variants. No correlations of alleles and/or genotypes of all examined
RAGE polymorphism with positive familiar history of psoriasis and/or
early onset of psoriasis manifestation (less than 40 years) were
found. The G82S, 1704G/T and 2245A/G RAGE polymorphisms were
associated neither with plaque psoriasis nor with personal history of
common diseases (diabetes mellitus, cardiovascular disorders, cancer,
allergy). Statistically significant rise in the 2184G allele frequency
of 2184A/G RAGE polymorphism was observed in psoriatics compared to
control group (odds ratio 1.40, 95% CI 0.88-2.21, P=0.005, after
correction for the number of comparisons Pcorr=0.02). The 2184G allele
occurred more often in psoriatic patients with negative personal
history of diabetes mellitus (odds ratio 1.07, 95% CI 0.69-1.64,
P=0.007) and with negative personal history of cardiovascular diseases
(odds ratio 1.7, 95% CI 1.08-2.07, P=0.001). The distribution of
common genotypes of the four polymorphisms (81 variants) did not
differ signficantly between psoriatic and control group. The
identification of novel susceptibility gene RAGE - provides some
insight into the precise biochemical pathway that control plaque
psoriasis manifestation. Because genetic background of psoriasis is
supposed to be multigenic, interaction with other several genes with
higher common relative genetic risk for psoriasis manifestation could
be expected. Complicated linkage disequilibria within HLA system genes
in 6p21.3 region cannot be excluded.
[i should find the pmid when i read this]
I'm reading it now:
http://www.ncbi.nlm.nih.gov/pubmed/12029499
PMID: 12029499
-------
So HLA-Dq is
http://en.wikipedia.org/wiki/HLA-DQ
[...]
Subunit
Name Gene Chromosomal
Locus
α HLA-DQA1 Chromosome 6p21.31
β HLA-DQB1 Chromosome 6p21.31
<snip>
37 hits on pubmed for keywrods: hla-dq psoria*
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=hla-dq+psoria*&log$=activity
Don't have time now to read these. But will soon. :)
OK, ok, my like my cats...
Let's peek at one.
For FUN.
www.ncbi.nlm.nih.gov/pubmed/18509540
Effective detection of human leukocyte antigen risk alleles in celiac
disease using tag single nucleotide polymorphisms.
Monsuur AJ, de Bakker PI, Zhernakova A, Pinto D, Verduijn W, Romanos
J, Auricchio R, Lopez A, van Heel DA, Crusius JB, Wijmenga C.
Department of Medical Genetics, University Medical Centre Utrecht,
Utrecht, The Netherlands.
Erratum in:
PLoS One. 2009;4(5) doi:10.1371/annotation/53480f56-4ef7-4877-ace7-
e5892d392cce.
BACKGROUND: The HLA genes, located in the MHC region on chromosome
6p21.3, play an important role in many autoimmune disorders, such as
celiac disease (CD), type 1 diabetes (T1D), rheumatoid arthritis,
multiple sclerosis, psoriasis and others. Known HLA variants that
confer risk to CD, for example, include DQA1*05/DQB1*02 (DQ2.5) and
DQA1*03/DQB1*0302 (DQ8). To diagnose the majority of CD patients and
to study disease susceptibility and progression, typing these strongly
associated HLA risk factors is of utmost importance. However, current
genotyping methods for HLA risk factors involve many reactions, and
are complicated and expensive. We sought a simple experimental
approach using tagging SNPs that predict the CD-associated HLA risk
factors. METHODOLOGY: Our tagging approach exploits linkage
disequilibrium between single nucleotide polymorphism (SNPs) and the
CD-associated HLA risk factors DQ2.5 and DQ8 that indicate direct
risk, and DQA1*0201/DQB1*0202 (DQ2.2) and DQA1*0505/DQB1*0301 (DQ7)
that attribute to the risk of DQ2.5 to CD. To evaluate the predictive
power of this approach, we performed an empirical comparison of the
predicted DQ types, based on these six tag SNPs, with those executed
with current validated laboratory typing methods of the HLA-DQA1 and -
DQB1 genes in three large cohorts. The results were validated in three
European celiac populations. CONCLUSION: Using this method, only six
SNPs were needed to predict the risk types carried by >95% of CD
patients. We determined that for this tagging approach the sensitivity
was >0.991, specificity >0.996 and the predictive value >0.948. Our
results show that this tag SNP method is very accurate and provides an
excellent basis for population screening for CD. This method is
broadly applicable in European populations.
PMID: 18509540 [PubMed - indexed for MEDLINE]
OK and it's Boring... LOL
So?
Is that why cats are like they ARE?
-----------
I want to be SUrE that i get the RAGE angle and AGE's in to this LPS/
Glutathione complex.
So lets keyword: psoria* advanced end products rage [ five hits
pubmed]
The most recent of these five:
www.ncbi.nlm.nih.gov/pubmed/18606705
Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor
for advanced glycation end products and potentiates inflammation with
highly homologous but functionally distinct S100A15.
Wolf R, Howard OM, Dong HF, Voscopoulos C, Boeshans K, Winston J, Divi
R, Gunsior M, Goldsmith P, Ahvazi B, Chavakis T, Oppenheim JJ, Yuspa
SH.
Laboratory of Cancer Biology and Genetics, Center for Cancer Research,
National Cancer Institute, Bethesda, MD 20892, USA.
Human S100A7 (psoriasin) is overexpressed in inflammatory diseases.
The recently discovered, co-evolved hS100A15 is almost identical in
sequence and up-regulated with hS100A7 during cutaneous inflammation.
The functional role of these closely related proteins for inflammation
remains undefined. By generating specific Abs, we demonstrate that
hS100A7 and hS100A15 proteins are differentially expressed by specific
cell types in the skin. Although highly homologous, both proteins are
chemoattractants with distinct chemotactic activity for leukocyte
subsets. We define RAGE (receptor for advanced glycation end products)
as the hS100A7 receptor, whereas hS100A15 functions through a Gi
protein-coupled receptor. hS100A7-RAGE binding, signaling, and
chemotaxis are zinc-dependent in vitro, reflecting the previously
reported zinc-mediated changes in the hS100A7 dimer structure. When
combined, hS100A7 and hS100A15 potentiate inflammation in vivo. Thus,
proinflammatory synergism in disease may be driven by the diverse
biology of these almost identical proteins that have just recently
evolved. The identified S100A7 interaction with RAGE may provide a
novel therapeutic target for inflammation.
PMID: 18606705 [PubMed - indexed for MEDLINE]
And the next one:
www.ncbi.nlm.nih.gov/pubmed/12832707
Expression of the pro-inflammatory protein S100A12 (EN-RAGE) in
rheumatoid and psoriatic arthritis.
Foell D, Kane D, Bresnihan B, Vogl T, Nacken W, Sorg C, Fitzgerald O,
Roth J.
Department of Pediatrics, University of Münster, Münster, Germany.
dfo...@uni-muenster.de
OBJECTIVES: Infiltration of synovial tissue by neutrophils is crucial
in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and
seronegative arthritis (SA). Altered vascular function and endothelial
activation are important in PsA. S100A12 (EN-RAGE) is secreted by
activated granulocytes and binds to the receptor for advanced
glycation end products, which induces nuclear factor (NF)-kappaB-
dependent activation of endothelium. METHODS: Immunohistochemical
studies were performed to detect synovial S100A12 expression. We
analysed serum and synovial fluid of 42 patients for S100A12 levels.
RESULTS: S100A12 was strongly expressed in inflamed synovial tissue
whereas it was nearly undetectable in synovia of controls or patients
after successful treatment. Serum levels of S100A12 correlated with
disease activity. CONCLUSIONS: Local expression of S100A12 in inflamed
tissue suggests a role in synovitis, especially in PsA. High serum
concentrations of S100A12 in patients with active arthritis compared
with healthy controls or patients in remission point to its usefulness
as a serum marker.
PMID: 12832707
And this one means, if your a psor head or more so a psoriatic with
PsA, then
you should use ALT-711 (aka- SYI-2074 & alagebrium from synvista)
Let's check Alt-711 for RA (
ALT-2074 is the topical for psoriasis:
http://www.bio-medicine.org/biology-technology-1/Synvista-Therapeutics-to-Develop-Topical-Formulation-of-ALT-2074-for-the-Treatment-of-Psoriasis-2633-1/
DAng nation how come their web site doesn't come uP?
I get other companies who want to sell their contacts to them. LOL
http://www.lead411.com/company_SynvistaTherapeuticsInc_Berkowitz_5817.html
Working with Advanced Glycosylation End-product (A.G.E.) pathway to
slow aging seems
like it would bring in some bucks.
Lets run the wiki again for other terms other then ALT-711 et al...
OK, here's one for the current product name:
http://en.wikipedia.org/wiki/Alagebrium
Alagebrium (formerly known as ALT-711) is a drug produced by Alteon
Corporation, which is currently being evaluated in clinical trials. It
is the first drug to be clinically tested for the purpose of breaking
the crosslinks caused by advanced glycation endproducts (A.G.E.s),
thereby reversing one of the main mechanisms of aging.[1]
<sniP>
And as it says they ran out of cash Alteon or synvista are both gone?
Go ahead and let me know if this opens:
http://www.alteon.com/
The wiki says that synvista should be up and running:
[...]
Although Alagebrium has shown very promising Phase I and II clinical
trials, active research stopped because Alteon had run out of
operating cash.[5] Alteon, having a huge amount of convertible
preferred stock hanging over its head (held by Genentech), had
increasing difficulty raising subsequent levels of venture capital
until finally, it was unavailable at any price. On 25 July, 2007
Alteon was essentially bought for its corporate shell by a three-man
operation developing another medication that needed a corporate shell
in order to move fast. The company changed its name to Synvista
Therapeutics, Inc. now with perhaps three employees in the United
States, and outsources its research, (probably none of it on
Alagebrium, despite the website's assertions).
<sniP>
Wow... all that and it's a fluke?
Or is big pharma taking their pot of gold?
Maybe they can market to supplement folks?
I hope the synvista guys have enough cash to do the PsA trials or some
RA ones.
Luckilly we can see what morelife has to say for it:
http://morelife.org/researchems/ALT-711.html
ALT-711 (Alagebrium Chloride)
A Promising Advanced Glycation Endproduct (AGE) Crosslink Breaker
Currently in Clinical Trials
Below we present a summary of the major research results for this
chemical (which has recently been given the generic name "alagebrium
chloride"), taken from published studies in the peer-reviewed
literature. For the latest information on the progress of this drug
towards establishment acceptance as a therapeutic modality for
recognized diseases, see Alteon Inc. - ALT-711 In its bromide form,
ALT-711 has also been called DMPTB [N-phenacyl-4,5-dimethylthiazolium
bromide] or PMTB and an earlier unmethylated form was called PTB.
<sniP>
See the end of this page if you wish to correspond with Kitty Antonik
Wakfer or Paul W.
or pay for value received from their site:
http://morelife.org/
After reading their bio's i want to give them something.
http://morelife.org/personal/index.html
But i bet i live longer then them .. lol
What more then ALA (alcar) with ALC and resveratrol and and and the
supplements i like already?
http://morelife.org/personal/health/index.html
====================
OK, that segue is history and the wafer paul matthews mystery right
with it. LOL
Back to RAGE and en-rage:
Only 20 hits for en-rage on pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=EN-RAGE&log$=activity
http://en.wikipedia.org/wiki/RAGE_(receptor)
RAGE, the receptor for advanced glycation endproducts is a 35kD
transmembrane receptor of the immunoglobulin super family which was
first characterized in 1992 by Neeper et al.[1]. Its name comes from
its ability to bind advanced glycation endproducts (AGE), a
heterogeneous group of non-enzymatically altered proteins. Besides
AGEs, RAGE is also able to bind other ligands and is thus often
referred to as a pattern recognition receptor.
The interaction between RAGE and its ligands is thought to result in
pro-inflammatory gene activation[2]. Due to an enhanced level of RAGE
ligands in diabetes or other chronic disorders, this receptor is
hypothesised to have a causative effect in a range of inflammatory
diseases such as diabetic complications, Alzheimer's disease and even
some tumors.
Isoforms of the RAGE protein, which lack the transmembrane and the
signalling domain (commonly referred to as soluble RAGE or sRAGE) are
hypothesized to counteract the detrimental action of the full-length
receptor and are hoped to provide a means to develop a cure against
RAGE-associated diseases.
<snip>
This wiki page calls it sRAGE...
And there are 161 returns for sRAGE on pubmed:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=srage&log$=activity
147 of those hits have the kicker: glycation
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=srage+glycation&log$=activity
16 hits for sRAGE glycation arthritis:
http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=srage+glycation+arthritis&log$=activity
Here's a typical from this list:
www.ncbi.nlm.nih.gov/pubmed/19591173
RAGE expression and NF-kappaB activation attenuated by extracellular
domain of RAGE in human salivary gland cell line.
Chuong C, Katz J, Pauley KM, Bulosan M, Cha S.
Oral Surgery and Diagnostic Sciences, College of Dentistry, University
of Florida, Gainesville, FL 32610, USA.
The receptor for advanced-glycation-end-products (RAGE) has been
implicated as a pro-inflammatory factor in chronic inflammatory
conditions such as diabetes mellitus and rheumatoid arthritis. The aim
of this study was to investigate the inhibitory effect of the soluble-
RAGE (sRAGE), the extracellular domain of RAGE, on RAGE expression and
NF-kappaB translocation in human-salivary gland-cell-lines (HSG).
Cells were stimulated with agonist S100A4, fusion protein of RAGE
encompassing the extracellular domain of RAGE (ex-RAGE), ex-RAGE
followed by S100A4, or S100A4 followed by ex-RAGE. Our study indicates
that RAGE expression was highest at 150 microg/microl of S100A4 and
efficiently down-regulated by 1.8-fold (P < 0.05) when ex-RAGE was
incubated prior to agonist S100A4. RAGE protein was also consistently
down-regulated by 20-40% with pre-incubation of ex-RAGE. More
importantly, nuclear translocation of p65 and p52 of NF-kappaB by
S100A4 was inhibited in the presence of ex-RAGE, confirming anti-
inflammatory function of ex-RAGE. In conclusion, ex-RAGE down-
regulates RAGE expression and inhibits p65 and p52 activation in HSG,
providing evidence that ex-RAGE functions as a "decoy" to RAGE-ligand
interaction and thus potentially dampening inflammatory conditions.
PMID: 19591173
Spinoffs from this?
Sure... try anyway.
WE have the calcium binding protein S100A4
But not S100A7 with en-rage or sRAGE:
But with S100A7
WE'd have is it's in the cards besides S100A4
http://en.wikipedia.org/wiki/S100A7
Protein S100-A7 is a protein that in humans is encoded by the S100A7
gene.[1]
The protein encoded by this gene is a member of the S100 family of
proteins containing 2 EF-hand calcium-binding motifs. S100 proteins
are localized in the cytoplasm and/or nucleus of a wide range of
cells, and involved in the regulation of a number of cellular
processes such as cell cycle progression and differentiation. S100
genes include at least 13 members which are located as a cluster on
chromosome 1q21. This protein differs from the other S100 proteins of
known structure in its lack of calcium binding ability in one EF-hand
at the N-terminus. This protein is markedly over-expressed in the skin
lesions of psoriatic patients, but is excluded as a candidate gene for
familial psoriasis susceptibility. The protein functions as a
prominent antimicrobial peptide mainly against E. coli.[2]
Interactions
S100A7 has been shown to interact with COP9 constitutive
photomorphogenic homolog subunit 5,[3] FABP5[4][5] and RANBP9.[6]
<sniP>
http://en.wikipedia.org/wiki/COP9_constitutive_photomorphogenic_homolog_subunit_5
COP9 constitutive photomorphogenic homolog subunit 5 (Arabidopsis),
also known as COPS5 or Csn5, is a gene conserved from humans to
Saccharomyces cerevisiae.[1]
The protein encoded by this gene is one of the eight subunits of COP9
signalosome, a highly conserved protein complex that functions as an
important regulator in multiple signaling pathways. The structure and
function of COP9 signalosome is similar to that of the 19S regulatory
particle of 26S proteasome. COP9 signalosome has been shown to
interact with SCF-type E3 ubiquitin ligases and act as a positive
regulator of E3 ubiquitin ligases. This protein is reported to be
involved in the degradation of cyclin-dependent kinase inhibitor
CDKN1B/p27Kip1. It is also known to be a coactivator that increases
the specificity of JUN/AP1 transcription factors.[1]
<sniP>
Oh well there are a few others.
But my team is playing and it's 14-3 and it's hard to watch and type.
LOL
So...
I'll mention AGE's as a ligand for RAGE (sRAGE and en-rage?)
Advanced glycation end product
http://en.wikipedia.org/wiki/Advanced_glycation_endproduct
A ligand for RAGE
http://en.wikipedia.org/wiki/RAGE_(receptor)#RAGE_ligands
also:
HMGB1 (Amphoterin)
S100b
Amyloid-β-protein
Mac-1
================
More to come. right now it's charger time... versus the eagles...
Will alt-711 now alagebrium become the sod/cat glutathione supplement
du jour?
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/browse_thread/thread/2ff35098d84c568f/c24323712cb6b428?hl=en&lnk=gst&q=sod+cat#c24323712cb6b428
There are 14 hits for sod cat..
And now ONE giant one for alagebrium.
randall....must watch football team, they could be gone