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Member
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Join Date: Jan 2008
Location: Maryland outside WASH DC
Posts: 258
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Member
Join Date: Jan 2008
Location: Maryland outside WASH DC
Posts: 258
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More MMP-9 & TIMP-1 comments
Here is a rather interesting exchange I had with Ed Hill related to this in Dec 2003.
Quote:
This is Ed Hill to me (jackD)
gonna pour a little skunked beer on this one...sorry.
jackD, you are absolutely right that modulation of MMP-9 in the CNS
helps us greatly.
and noodling TIMP (Tissue Inhibitors of MetalloProteinses) production
thereby correcting the TIMP/MMP imbalance long known to be common to
MSrs is a tempting target.
apologies to those already up on the following.
think MMP as open hand with zinc ion in the palm. the zinc ion when
exposed breaks down certain proteins by busting up weak hydrogen bonds
on contact.
TIMPs might best be seen as a second hand closing over the first,
fingers entwined so blocking contact between the zink ion and other
proteins.
normally, like most other MMPs 9 travels with it's TIMP in tow doing
no harm. there are a few ways to remove the TIMP and activate the
zinc ion. and in some cases, particularly in the MS CNS there aren't
enough TIMPs to go around.
MMP-9 has been shown to cut through the vessel walls of the BBB making
way for immune system elements to get in. and inside the CNS it does
all kinds of damage.
on the other hand...
MMP-9 is a working part of the extracellular matrix. that's the gooey
space between cells. when cells die or eject some garbage, MMP-9 is a
major factor in cutting the junk into nice littel bits and sending 'em
off to the lymphatics.(the "other" circulatory system) from whence
they are shuffled out the poopshoot.
this makes noodling with the matrixins a tad tricky at best. MMP-9 is
also the main cutting tool allowing mensus and ovulation. you didn't
think the eggs just pop up on their own did you? that's a whole
article in itself.
i've written here 'bout this in days of yore.
it might just be the reason for women being struck more frequently by autoimmunity.
their whole MMP regulatory system is flipped over and rebooted every
month. that's a risky biz in my book.
anyways...
oncologists have been fiddling with MMP-9 among others because they
facilitate tumor vascularization. arthritis aka rheumatologists have
also done some great work in this area.
the catch?
THE SIDE EFFECTS SUCK!!!!
it's kind of like shutting down garbage collections because the trucks
smell bad.
great fer a few days. but soon the garbage piles up and it's not very pretty.
regards
ed
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MORE FORMAL STATEMENT OF THE SAME STUFF
Quote:
1: Neuroscientist 2002 Dec;8(6):586-95
Matrix metalloproteinases and neuroinflammation in multiple sclerosis.
Rosenberg GA.
Department of Neurology, University of New Mexico Health Sciences Center,
Albuquerque, New Mexico 87131, USA.
Matrix metalloproteinases (MMPs) are extracellular matrix remodeling neutral
proteases that are important in normal development, angiogenesis, wound repair,
and a wide range of pathological processes.Growing evidence supports a key role
of the MMPs in many neuroinflammatory conditions, including meningitis,
encephalitis, brain tumors, cerebral ischemia, Guillain-Barre, and multiple
sclerosis (MS).
The MMPs attack the basal lamina macromolecules that line the
blood vessels, opening the blood-brain barrier (BBB). They contribute to the
remodeling of the blood vessels that causes hyalinosis and gliosis, and they
attack myelin. During the acute inflammatory phase of MS, they are involved in
the injury to the blood vessels and may be important in the disruption of the
myelin sheath and axons. Normally under tight regulation, excessive proteolytic
activity is detected in the blood and cerebrospinal fluid in patients with acute
MS. Because they are induced in immunologic and nonimmunologic forms of
demyelination, they act as a final common pathway to exert a "bystander" effect.
Agents that block the action of the MMPs have been shown to reduce the damage to
the BBB and lead to symptomatic improvement in several animal models of
neuroinflammatory diseases, including experimental allergic encephalomyelitis.
Such agents may eventually be useful in the control of excessive proteolysis
that contributes to the pathology of MS and other neuroinflammatory conditions.
PMID: 12467380 [PubMed - in process]
: Semin Cell Dev Biol. 2008 Feb;19(1):42-51. Epub 2007 Jun 19.
MMPs in the central nervous system: where the good guys go bad.
Agrawal SM, Lau L, Yong VW.
Hotchkiss Brain Institute and the Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada.
Matrix metalloproteinases (MMPs) are expressed in the developing, healthy adult and diseased CNS. We emphasize the regulation of neurogenesis and oligodendrogenesis by MMPs during CNS development, and highlight physiological roles of MMPs in the healthy adult CNS, such as in synaptic plasticity, learning and memory.
Nonetheless, MMPs as "the good guys" go bad in neurological conditions, likely aided by the sudden and massive upregulation of several MMP members.
We stress the necessity of drawing a fine balance in the treatment of neurological diseases, and we suggest that MMP inhibitors do have therapeutic potential early after CNS injury.
PMID: 17646116 [PubMed - indexed for MEDLINE]
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Last edited by Chemar; 06-20-2008 at 02:57 PM.
Reason: adding quote tags
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