Maximize beta interferons and lessen MS damage

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Maximize beta interferons and lessen MS damage

Postby jackD » Tue Jan 19, 2010 10:01 am

(Neuroscientist 2002 Dec)(see last abstract)

MMP-9s KILL the activity of ALL IFN-Betas.

It is a VERY GOOD IDEA to lower MMP-9s if taking an Ifn-Beta drug.

If you want to maximize Avonex (or any beta interferon), lowering MMP-9s will prevent it from being degraded by being cleaved into parts thus killing its Activity/Effectiveness. ... fault.aspx

Also getting the most activity from the least amount of near natural (human) interferon like Avonex will usually result in MUCH LESS neutralizing antibody formation (2-5% vrs 20-26%).

Things that reduce MMP-9s (AKA gelatinase B)

***NOTE*** ( gelatinase B = MMP-9) ***NOTE***
QUERCETIN..........................REDUCES MMP-9s

VIT D3 .................................REDUCES MMP-9s

RESVERATROL (Grape Skin Extract) ...REDUCES MMP-9s


ALPHA LIPOIC ACID (R-lipoic/ R-Dihdro-LipoicAcid) ... REDUCES MMP-9s

NAC N-Acetyl-L-Cysteine .......REDUCES MMP-9s

STATIN DRUGS (i.e Zocor) .....REDUCES MMP-9s

Omega-3s (ie Fish oil) ...........REDUCES MMP-9s

Minocycline/Doxycycline.........REDUCES MMP-9s

Curcumin.............................REDUCES MMP-9s

Pycnogenol (Pine bark extract)..REDUCES MMP-9s

Chondroitin sulfate (CS) and CS plus glucosamine sulfate (GS) ..REDUCES MMP-9s

Interferon Betas 1a/1b...........REDUCES MMP-9s

(of course Steroids ....REDUCES MMP-9s)

I have lots more information on this MMP - MS - INTERFERON-beta connection and will elaborate it if there is some interest in this subject here. For the real techie stuff check the link shown below
(see fig 2 and narrative on page 505)
Matrix metalloproteinases and their multiple roles in
neurodegenerative diseases


Lancet Neurol. 2003 Dec;2(12):747-56.

Functional roles and therapeutic targeting of gelatinase B and chemokines in
multiple sclerosis.

Opdenakker G, Nelissen I, Van Damme J.
GO, IN, and JVD are at the Rega Institute for Medical Research, University
Leuven, Belgium

Multiple sclerosis (MS) is a demyelinating disease of the CNS of unknown
cause. Pathogenetic mechanisms, such as chemotaxis, subsequent activation of autoreactive lymphocytes, and skewing of the extracellular proteinase balance, are targets for new therapies.

Matrix metalloproteinase gelatinase B (MMP-9) is upregulated in MS and was recently shown to degrade interferon beta, one of the drugs used to treatMS.

Consequently, the effect of endogenously produced interferon beta or
parenterally given interferon beta may be increased by gelatinase B
inhibitors. Blockage of chemotaxis or cell adhesion molecule engagement, and inhibition of hydoxymethyl-glutaryl-coenzyme-A reductase to lower expression of gelatinase B, may become effective treatments of MS, alone or in combination with interferon beta. This may allow interferon beta to be used at lower doses and prevent side-effects.

PMID: 14636780 [PubMed - in process]

1: Brain. 2003 Jun;126(Pt 6):1371-81.

Gelatinase B/matrix metalloproteinase-9 cleaves interferon-beta and is a
target for immunotherapy.

Nelissen I, Martens E, Van den Steen PE, Proost P, Ronsse I, Opdenakker G.
Rega Institute for Medical Research, Laboratory of Molecular Immunology,
University of Leuven, Leuven, Belgium.

Parenteral administration of interferon (IFN)-beta is one of the currently
approved therapies for multiple sclerosis. One characteristic of this
disease is the increased production of gelatinase B, also called matrix
metalloproteinase (MMP) 9. Gelatinase B is capable of destroying the
blood-brain barrier, and of cleaving myelin basic protein into
immunodominant and encephalitogenic fragments, thus playing a functional
role and being a therapeutic target in multiple sclerosis. Here we
demonstrate that gelatinase B proteolytically cleaves IFN-beta, kills its
activity, and hence counteracts this cytokine as an antiviral and
immunotherapeutic agent. This proteolysis is more pronounced with
IFN-beta-1b than with IFN-beta-1a. Furthermore, the tetracycline
minocycline, which has a known blocking effect in experimental autoimmune
encephalomyelitis, an in vivo model of acute inflammation in multiple
sclerosis, and other MMP inhibitors prevent the in vitro degradation of
IFN-beta by gelatinase B. These data provide a novel mechanism and rationale
for the inhibition of gelatinase B in diseases in which IFN-beta has a
beneficial effect. The combination of gelatinase B inhibitors with better
and lower pharmacological formulations of IFN-beta may reduce the
side-effects of treatment with IFN-beta, and is therefore proposed for
multiple sclerosis therapy and the immunotherapy of viral infections.

PMID: 12764058 [PubMed - indexed for MEDLINE]

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.


PMID: 12467380 [PubMed - in process]
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Postby jimmylegs » Tue Jan 19, 2010 12:01 pm

pretty cool :) don't forget zinc! LOL

it can reduce MMP-9s and also helps response to interferon (IFN-a2b that is)

Zinc deficiency impairs wound healing of colon anastomosis in rats
Background Anastomotic leakage is a relevant surgical complication. The aim of the study was to investigate the influence of a controlled preoperative zinc deficiency on the extracellular matrix composition of colon anastomosis.
Materials and methods Forty male Wistar rats were randomized to either a zinc deficiency group (n = 20) or a control group (n = 20). In each animal, a transverse colonic end-to-end anastomosis was performed. On postoperative day 7, the surface of the mucosal villi, expression of matrix metalloproteinases (MMP) 2, 8, 9, and 13, and both the number of proliferating cells (Ki67) and apoptotic cells, as well as the collagen types I/III ratio were analyzed. Within the anastomotic area the mesenterial region and the antimesenterial region were analyzed separately.
Results In each group, one anastomotic leakage was detected. Expression of both MMP 2, 9, and 13 was significantly higher, and expression of Ki67 was significantly reduced in the zinc deficient group both mesenterial and antimesenterial. The collagen types I/III ratio was reduced in the zinc deficiency group by trend, without statistical significance neither mesenterial nor antimesenterial. Likewise, zinc deficiency affected neither the expression of MMP 8 nor the rate of apoptotic cells, respectively. Analyses of the surface of the mucosal villi revealed no significant differences comparing the groups with neither mesenterial nor antimesenterial.
Conclusions Our study constitutes the known negative effect of zinc deficiency on wound healing. Zinc deficiency significantly increased the activity of MMPs (2, 9, and 13), caused a reduced collagen type I/III ratio, and delayed cell proliferation and quality of intestinal wound healing.

Serum zinc as a factor predicting response to interferon-α2b therapy in children with chronic hepatitis B
Although it has been unclear why more than 50% of children with chronic hepatitis B virus infection do not respond to interferon therapy, in some instances resistance to interferon probably is caused by an inability to stimulate appropriately cellular immune responses to hepatitis B virus. It is known that immune integrity is tightly linked to zinc status. We examined the relationship between serum zinc levels and response to interferon (INF)-α therapy in children with chronic hepatitis B. Twenty-five children with chronic hepatitis B infection were injected with 5 × 106 units/m2 recombinant IFN-α 2b subcutaneously three times weekly for 9 mo. Children were followed for at least 9 mo after the end of therapy.
Sustained response was obtained in eight (32%) patients. Although initial serum zinc and alanine aminotransferase levels were significantly higher; initial hepatitis B Virus (HBV)-DNA values, hepatic activity index, periportal necrosis, and fibrosis scores were significantly lower in sustained responders than in nonresponders. Mean baseline serum zinc, alanine aminotransferase and HBV-DNA values, histologic activity index, periportal necrosis, and fibrosis scores were predictive of response to IFN-α 2b therapy. These findings suggest that serum zinc levels might be used as a factor predicting response to interferon-α 2b therapy, and so may help in identifying those children with a better chance of response.

personally i don't take beta interferon - i just try to get my good dietary/supplementary interferon boosters, like good ol' vit c :)
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Postby jackD » Tue Jan 19, 2010 12:54 pm

There are two METALS that are a problem for MS folks.


Some ZINC is good and necessary for good health however HIGH levels of ZINC is highly suspected of causing MS. Several "hot clusters" of MS have been found around locations where high levels of zinc were being released.

I do not think it would be wise for a person with MS to take ZINC supplements beyond 25 mg (167 %DV) that is in most multivitamins.

I think this may have something to to with MMP formation. All 27 types of MMPs have a zinc at the "business end" and use it to cut our Myelin into little pieces by breaking the hydrogen bonds. I think that the body may adapt to the high levels of ZINC by making LOTS of "very agressive" MMPs.

MMPs levels are elevated JUST BEFORE and DURING an MS attack.

: J Neuroimmunol. 1997 Feb;72(2):155-61.

Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an

Chandler S, Miller KM, Clements JM, Lury J, Corkill D, Anthony DC, Adams SE,
Gearing AJ.

British Biotech Pharmaceuticals Limited, Cowley, Oxford, UK.

The matrix metalloproteinases (MMPs) are a family of at least 14 zinc-dependent enzymes which are known to degrade the protein components of extracellular matrix. In addition, MMPs and related enzymes can also process a number of cell surface cytokines, receptors, and other soluble proteins. In particular we have shown that the release of the pro-inflammatory cytokine, tumor necrosis factor-alpha, from its membrane-bound precursor is an MMP-dependent process.

MMPs are expressed by the inflammatory cells which are associated with CNS lesions in animal models of multiple sclerosis (MS) and in tissue from patients with the disease. MMP expression will contribute to the tissue destruction and inflammation in MS. Drugs which inhibit MMP activity are effective in animal models of MS and may prove to be useful therapies in the clinic.

Publication Types:
Review, Tutorial

PMID: 9042108 [PubMed - indexed for MEDLINE]

1: Arch Environ Health. 2001 Sep-Oct;56(5):389-95.

Comment in:
Arch Environ Health. 2002 Jul-Aug;57(4):383; author reply 383.

A multiple sclerosis cluster associated with a small, north-central Illinois

Schiffer RB, McDermott MP, Copley C.

Department of Neuropsychiatry, Texas Tech University Health Sciences Center,
Lubbock 79430, USA.

The authors investigated a reported incidence cluster of multiple sclerosis (MS)cases in a small, north-central Illinois community to determine validity and statistical significance. DePue, Illinois--a small, north-central Illinois community--has previously been the site of significant environmental heavy-metal exposure from a zinc smelter. Significant contamination of soil and water with zinc and other metals has been documented in this community during the time period of interest. In the mid-1990s, several cases of MS were reported to the
Illinois Department of Public Health within the geographic limits of this
community. Available medical records from purported MS cases reported to the Illinois Department of Public Health were reviewed, and living individuals were seen and examined. Statistical analyses were conducted with clinically definite MS cases; onset dates were determined by first symptom, and expected incidence rates were determined from published epidemiologic studies. Nine new cases of clinically definite MS occurred among residents of DePue, Illinois, during the period between 1971 and 1990. Seven of the 8 living subjects included in the final analyses were examined by one author (RS).

The computed incidence rate deriving from these cases within DePue Township, Illinois, represented a statistically significant excess of new MS cases over expected. During the period from 1971 through 1990, a significant excess of MS cases occurred within the population of DePue, Illinois.

Significant exposure of this population to mitogenic trace metals, including zinc, was also documented during this time period.

PMID: 11777019 [PubMed - indexed for MEDLINE]
Neurology. 1994 Feb;44(2):329-33.

A genetic marker and family history study of the upstate New York multiple sclerosis cluster.
Schiffer RB, Weitkamp LR, Ford C, Hall WJ.

Department of Neurology, University of Rochester School of Medicine and Dentistry, NY 14642.

We report nine additional cases of new-onset multiple sclerosis (MS) among employees of an upstate New York manufacturing plant that uses zinc as a primary metal. These cases, identified during the decade 1980 to 1989, had clinical onset of the disease between 1979 and 1987. The new cases confirm the increased incidence of MS previously reported in the plant population for the 1970 to 1979 decade. The MS subjects in this occupationally based cluster do not seem different from other MS patients with regard to rates of familial MS or the frequencies of alleles for human leukocyte (HLA-DR) antigens or transferrin. The frequency distribution of alleles for transferrin (an iron- and zinc-binding protein) may differ in these and other MS subjects compared with controls.

PMID: 8309585 [PubMed - indexed for MEDLINE]

Neurology. 1987 Oct;37(10):1672-7.

Multiple sclerosis and the workplace: report of an industry-based cluster.
Stein EC, Schiffer RB, Hall WJ, Young N.

Department of Preventive and Community Medicine, University of Rochester School of Medicine and Dentistry, NY 14642.

Eleven cases of MS occurred within a 10-year period in a zinc-related manufacturing plant. The observed disease incidence was greater than expected from population data, using multiple approaches to statistical analysis (p less than or equal to 0.01). A case-control study, performed to examine several zinc parameters in blood, failed to indicate specific abnormalities among the MS patients, but all subjects (both MS and controls) working in the plant demonstrated higher serum zinc levels than all subjects (MS and controls) not working there.

PMID: 3658175 [PubMed - indexed for MEDLINE]
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Postby jimmylegs » Tue Jan 19, 2010 2:09 pm

ms-ers tend to be lower in zinc than controls, and on my part i was seriously deficient. the normal range includes the ms range and it's not good enough to have 'normal' zinc levels. there are a few studies out there looking at zinc in healthy controls. one of them has a really good n, up near 2000 if i remember right. 18.2umol/L is the average serum zinc in healthy controls in that study. that's up near the top of the 'normal' range. my first zinc test came back 8.6 BAD
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Too little is bad,just enough is Great, too much is VERY BAD

Postby jackD » Tue Jan 19, 2010 9:19 pm

YES! It seems that zinc is low in the white matter of MS folks, so making sure
that you get a100% supply does make sense. You should not exceed 30 mg
daily. A 100 % dose would be 15 mg.
A chelated form of zinc called zinc monomethionine (zinc bound with the
amino acid methionine) is sold under the trademark OptiZinc has been found
to have antioxidant activity comparable to that of Vitamin C, Vitamin E, and
beta-carotene. It is readily absorbed by the body in this form.
Too much zinc can cause MS by increasing numbers/intenstity of activity of MMPs. The main component that does the myelin damage is the MMP-9s using the Zinc as a 'knife".
(see fig 2 and narrative on page 505)

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Matrix metalloproteinases MMPs in multiple sclerosis

Postby jackD » Fri Feb 19, 2010 5:10 pm

My doctor(Christopher T. Bever) seems to agree with me and has stated his opinion in this editorial in the Neurology Journal. Some MMPs do GOOD things necessary for myelin repair. Excessive MMP-9s seem to do far more BAD things then GOOD.
. ... mmp-ms.doc

Matrix metalloproteinases in multiple sclerosis
Targets of therapy or markers of injury?

Christopher T. Bever, Jr., MD and Gary A. Rosenberg, MD

From the Neurology and Research Services, VA Maryland Health Care System, and the Departments of Neurology and Pharmacology and Experimental Therapeutics (Dr. Bever), School of Medicine, University of Maryland, Baltimore, MD; and Departments of Neurology, Neuroscience, and Cell Biology and Physiology (Dr. Rosenberg), University of New Mexico School of Medicine, Albuquerque, NM.

Address correspondence and reprint requests to Dr. Christopher Bever, Maryland Center for Multiple Sclerosis, 22 S. Greene St., N4W49, Baltimore, MD 21201.

Interferon-beta (IFNß) treatment represents a major advance in the management of MS that was made without a complete understanding of the cause of MS or the mechanism of action of IFNß. It is widely believed that MS is an immune-mediated disease and that the mechanism of action of IFNß is related to its immunomodulatory activity. In December 1996, two articles1,2 and an editorial3 were published that proposed, based on in vitro studies, that the therapeutic effect of IFNß in MS might be caused by an inhibition of matrix metalloproteinase-9 (92-kDa type IV collagenase or MMP-9). Transmigration of activated lymphocytes across basement membranes is dependent on secreted MMP-9, and the two studies showed that IFNß decreased MMP-9 secretion and lymphocyte transmigration across an artificial basement membrane. It was proposed that IFNß treatment blocked lesion formation in MS by limiting the entry of lymphocytes into the CNS. If this hypothesis is true, then lymphocytic-secreted MMP-9 activity should increase before the appearance of new lesions and secreted MMP-9 activity should decrease during treatment with IFNß in MS patients. This issue of Neurology contains two articles examining these questions in patients with MS, specifically following serum levels of MMP-9. Both provide data that support the hypothesis. Waubant et al.4 examined serum levels of MMP-9 and its inhibitor, tissue inhibitor to metalloproteinase-1 (TIMP-1), in patients with MS in a natural history study of patients undergoing monthly gadolinium-enhanced brain MRI scans. They found that MMP-9 levels increased without significant change in TIMP-1 immediately before the appearance of new gadolinium-enhancing MRI lesions. The second article, by Trojano et al.,5 examined changes in serum MMP-9 levels in patients during treatment with IFNß-1b. They found a decrease during the first year of treatment, which correlated with clinical and MRI evidence of therapeutic effect. Soluble intercellular adhesion molecule levels that correlate inversely with lymphocyte trafficking were also measured and were low before treatment but increased during treatment. Serum levels of MMP-2 (72-kDa type IV collagenase), which is normally present in brain and which may correlate with injury, were also measured and did not change. These results suggest that serum MMP-9 levels reflect blood–brain barrier (BBB) damage in patients with MS but do not clarify whether they are causing the damage. The results are consistent with the hypothesis that MMP-9 from lymphocytes is required for migration across the BBB and that IFNß inhibits MMP-9, blocking lesion formation. Because the cellular origins of MMP-9 were not determined and there were no direct measures of lymphocyte trafficking across the BBB in either study, other interpretations are possible. This hypothesis will be more directly tested in the near future when inhibitors of MMP-9 are tested in therapeutic trials in MS patients.

MMPs and TIMPs are present in brain and their levels change in other pathologic conditions.6 Even if MMPs do not prove to be a useful therapeutic target,7 determination of serum levels may prove to be a valuable marker of disease activity and treatment response in MS. Brain cells as well as circulating white blood cells make MMPs. Both MMP-2 and MMP-9 open the BBB by hydrolysis of type IV collagen, fibronectin, and laminin in the basal lamina. MMP-2 is normally present in brain and CSF, whereas MMP-9 is induced during inflammation and is under the control of the activator protein–1 (AP-1) and nuclear factor-kappa-ß sites in the promoter region of the gene. Astrocytes make MMP-2 normally and express MMP-9 during inflammatory stimulation. Microglia primarily produce MMP-9, and endothelial cells also express MMP-9. Cytokines stimulate the secretion of MMPs. Intracerebral injection of tumor necrosis factor- induces MMP-9 with peak levels occurring after 24 hours coincident with peak BBB damage.8 Intracerebral injection of MMP-2 opens the BBB, and TIMP-2 reverses the injury.9 A synthetic MMP inhibitor blocks BBB injury in experimental allergic encephalomyelitis. Studies in humans support those in experimental animals. MMP-9 is elevated in the CSF of patients with MS10 particularly during MS exacerbation and is dramatically lowered by high-dose corticosteroid treatment.11 Corticosteroids regulate MMP-9 in vitro by blocking the AP-1 transcription site. The two studies in this issue showing elevation of serum MMP-9 before the appearance of new gadolinium-enhancing MRI lesions4 and a reduction with IFNß treatment5 take this work an important step further. They offer the possibility of a serum marker of BBB opening and tissue injury in patients with MS. Although the serum changes appeared before MRI changes, simultaneous activation of the MMPs in the brain may have facilitated the breakdown of the BBB, which required more time to be seen by MRI. Further studies confirming these results and determining their relationship to changes in the brain will clarify the clinical utility of serum MMP-9 levels in monitoring MS disease activity and responses to treatment.

MMPs and their inhibitors have been studied extensively in inflammation, which may provide insight into the pathophysiology of the relapsing-remitting and chronic progressive subtypes of MS. Tissue MMP activity reflects a balance between MMPs and TIMPs. In acute inflammation, extracellular MMP activity is responsive to cytokines, leading to proteolysis of extracellular matrix and basement membranes. TIMPs are produced to restore normal MMP balance as part of the repair process. However, inhibition of MMPs will lead to extracellular matrix deposition. In chronic inflammatory states in other tissues, excessive TIMP production is associated with fibrosis and thickened blood vessels.12 In the brain, acute inflammation generally results in a cytokine-driven increase in MMP-9. Repair in tissues occurs through a shift to MMP-2 and TIMP secretion under the control of growth factors, such as transforming growth factor-ß. We hypothesize that, early in MS lesion development, increases in MMP-9 predominate with subsequent BBB damage. Later, as a lesion matures and repair processes take over, TIMPs and MMP-2 participate in the remodeling of extracellular matrix, which may correspond with the chronic progressive stage of MS. Changes in tissue MMPs and TIMPs may be reflected in serum and CSF, providing a useful window on this process. Further study is now needed to define long-term changes in serum MMPs and TIMPs and to determine whether changes correlate with disease subtype and responses to treatment throughout the course of MS.

1. Leppert D, Waubant E, Burk MR, Oksenberg JR, Hauser SL. Interferon beta-1b inhibits gelatinase secretion and in vitro migration of human T cells: a possible mechanism for treatment efficacy in multiple sclerosis. Ann Neurol 1996;40:846–852.[Medline]
2. Stuve O, Dooley NP, Uhm JH, et al. Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9. Ann Neurol 1996;40:853–863.[Medline]
3. Hartung H-P, Kieseier BC. Targets for the therapeutic action of interferon-beta in multiple sclerosis. Ann Neurol 1996;40:825–826.[Medline]
4. Waubant E, Goodkin DE, Gee L, et al. Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis. Neurology 1999;53:1397–1401.[Abstract/Free Full Text]
5. Trojano M, Avolio C, Liuzzi GM, et al. Changes of serum ICAM-1 and MMP-9 induced by rIFNß-1b treatment in relapsing-remitting MS. Neurology 1999;53:1402–1408.[Abstract/Free Full Text]
6. Lukes A, Mun-Bryce S, Lukes M, Rosenberg GA. Extracellular matrix degradation by metalloproteinases and central nervous system diseases. Mol Neurobiol 1999;19:255–272.[Medline]
7. Kieseier BC, Seifert T, Giovannoni G, Hartung H-P. Matrix metalloproteinases in inflammatory demyelination: targets for treatment. Neurology 1999;53:20–25.[Abstract/Free Full Text]
8. Rosenberg GA, Estrada EY, Dencoff JE, Stetler-Stevenson WG. TNF- -induced gelatinase ß causes delayed opening of the blood-brain barrier: an expanded therapeutic window. Brain Res 1995;703:151–155.[Medline]
9. Rosenberg GA, Kornfeld M, Estrada E, Kelley RO, Liotta LA, Stetler-Stevenson WG. TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase. Brain Res 1992;576:203–207.[Medline]
10. Gijbels K, Masure L, Carton H, Opdenakker G. Gelatinase in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological diseases. J Neuroimmunol 1992;41:29–34.[Medline]
11. Rosenberg GA, Dencoff JE, Correa N, Reiners M, Ford CC. Effects of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to blood-brain barrier injury. Neurology 1996;46:1626–1632.[Abstract]
12. Stetler-Stevenson WG. Dynamics of matrix turnover during pathologic remodeling of the extracellular matrix. Am J Pathol 1996;148:1345–1350.[Medline]

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Matrix metalloproteinases MMP and neurodegenerative diseases

Postby jackD » Fri Feb 19, 2010 5:12 pm

Gary A Rosenberg MD the co-author of the above MMP Editorial wrote this very good paper on MMPs - Matrix metalloproteinases.


Matrix metalloproteinases and their multiple roles in
neurodegenerative diseases ... inases.pdf
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good guys go bad - the MMP-9s

Postby jackD » Fri Feb 19, 2010 5:25 pm

Well stated.


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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