Another confirmation of JNK needing more research.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=125674&CultureCode=en
Scientists from the Florida campus of The Scripps Research Institute
(TSRI) have defined the molecular structure of an enzyme as it interacts
with several proteins involved in outcomes that can influence
neurodegenerative disease and insulin resistance. The enzymes in
question, which play a critical role in nerve cell (neuron) survival,
are among the most prized targets for drugs to treat brain disorders
such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral
sclerosis (ALS).
The study was published online ahead of print on November 8, 2012, by the journal Structure.
The new study reveals the structure of a class of enzymes called
c-jun-N-terminal kinases (JNK) when bound to three peptides from
different protein families; JNK is an important contributor to
stress-induced apoptosis (cell death), and several studies in animal
models have shown that JNK inhibition protects against
neurodegeneration.
“Our findings have long-range implications for drug discovery,” said
TSRI Professor Philip LoGrasso, who, along with TSRI Associate Professor
Kendall Nettles, led the study. “Knowing the structure of JNK bound to
these proteins will allow us to make novel substrate competitive
inhibitors for this enzyme with even greater specificity and hopefully
less toxicity.”
The scientists used what they called structure class analysis,
looking at groups of structures, which revealed subtle differences not
apparent looking at them individually.
“From a structural point of view, these different proteins appear to
be very similar, but the biochemistry shows that the results of their
binding to JNK were very different,” he said.
LoGrasso and his colleagues were responsible for creating and solving
the crystal structures of the three peptides (JIP1, SAB, and ATF-2)
with JNK3 using a technique called x-ray crystallography, while Nettles
handled much of the data analysis.
All three peptides have important effects, LoGrasso said, inducing
two distinct inhibitory mechanisms—one where the peptide caused the
activation loop to bind directly in the ATP pocket, and another with
allosteric control (that is, using a location on the protein other than
the active site). Because JNK signaling needs to be tightly controlled,
even small changes in it can alter a cell’s fate.
“Solving the crystal structures of these three bound peptides gives
us a clearer idea of how we can block each of these mechanisms related
to cell death and survival,” LoGrasso said. “You have to know their
structure to know how to deal with them.”
The first authors of the study, “Structural Mechanisms of Allostery
and Autoinhibition in JNK Family Kinases,” which will appear in the
December 5, 2012 print edition of Structure, are John D.
Laughlin and Jerome C. Nwachukwu of TSRI. Other authors include Mariana
Figuera-Losada and Lisa Cherry, also of TSRI.
The study was supported by the National Institutes of Health (grant number NS057153).
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Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
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