CRMP-2, Oxidative Stress, CCSVI and MS

[Johnnymac]

Don't post much anymore but after reading http://www.pharmpro.com/News/2012/04/Ag ... -Sclerosis which was posted over on the CCSVI facebook page earlier it got me thinking about how it could be a piece of the puzzle. Went back and reviewed some of my old notes on oligodendrocytes apoptosis, and then came across this study http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract in the Journal of Neurochemistry. Only able to read the abstract but I wonder if this modified protein malfunctions in presence of oxidative stress triggering the apoptosis and in turn starts a kind snowball effect that some people's body are able to handle better than others.

Just thinking out loud here, curious to hear folks thoughts on this topic.

[cheerleader]

Hi Johnny--
good to hear from you. Your point on how it malfunctions in oxidative stress is a good one. It appears to malfunction in Alzheimer's, as well. I just wish the researchers would focus on mechanism of injury and preventative measures. Did you notice in the paper you linked how this process was reversed with antioxidants? That paper was a great find. Nice work!
Here were my thoughts on this from another thread -- and why I posted in on FB this morning.

What the researchers fail to mention is that this protein is found in neurodegenerative diseases and ischemic stroke. It's involved in axonal guidance, and comes in after injury.

Collapsin response mediator protein2 (CRMP2) is a brain-specific protein involved in neuronal polarity and axonal guidance, and phosphorylation of CRMP2 regulates the function and the activity. CRMP2 has shown to be implicated in several neurodegenerative diseases (Alzheimer's disease, epilepsy and ischemia)

http://www.ncbi.nlm.nih.gov/pubmed/21333637
http://www.springerlink.com/content/l32u81587278q64t/
http://www.landesbioscience.com/journal ... 1947614191
http://www.springerlink.com/content/t822327418652p81/

Here's a study on modulating CRMP 2 in Alzheimers

In another study, we have recently found that CRMP-2 interacts with Specifically Rac1-Associated protein (Sra-1/CYFIP1) (43a), which directly interacts with actin filaments (45). Thus, CRMP-2 may associate with actin filaments through Sra-1 in growth cones. In this study, Rho kinase-induced phosphorylation of CRMP-2 had no effect on the actin binding ability of CRMP-2. CRMP-2 is a highly conserved phosphoprotein, and its phosphorylation states alter upon NGF-induced neuronal differentiation or in the formation of degenerating neurites in the brains of patients with Alzheimer's disease (12, 33). These findings raise the possibility that other kinases up- or down-regulate CRMP-2 activity and mediate actin reorganization in the Rho family GTPase-mediated signal cascade. Further studies characterizing the protein kinases may shed some light on other functions of CRMP-2.

http://mcb.asm.org/content/25/22/9973.full

and I don't think the full role of CRMP 2 is understood just yet. The Australian MS study used EAE in mice-

Since CRMP-2 is present in adult and aged brains, there is reason to speculate that it may have a role in neuritic and axonal growth and regeneration and thus contribute to a high level of plasticity in adult brains. In some disease states, CRMP-2 has been shown to be reduced, such as in Down syndrome fetal brain, epilepsy brain hippocampus and areas of traumatic brain injury. In Alzheimer’s disease, CRMP-2 has been shown to be associated with the paired helical filaments (PHF) in degenerating neurons. This PHF-associated CMPR-2 has been shown to be highly phosphorylated. This hyperphosphorylated form of CMPR-2 may lead to its inactivation and may accelerate the neuritic degeneration in Alzheimer’s disease.

http://www.swimmunology.com/crmp-2-c.htm
cheer

[1eye]

A goat antiserum to a synthetic peptide that corresponds to amino acids 543-557of the C-terminus of the human CRMP-2

What the heck is a goat anti-serum?

[NHE]

A goat antiserum to a synthetic peptide that corresponds to amino acids 543-557of the C-terminus of the human CRMP-2

What the heck is a goat anti-serum?

An antibody.

[MarkW]

Hello Jonnymac,
Thanks for giving us more pieces of the puzzle that is the etiology of MS. I favour astrocyctes as an early factor but epigenesis of those 57 genes (common in pwMS) has to be before astrocytes (genes control human development).
Does CCSVI have genes controlling it?? An idea if CCSVI is common to other neuro-degenerative diseases.
More questions on why CCSVI/MS. I stick to "treat the symptom of CCSVI syndrome" as my recommendation because there are too many pieces in the puzzle for me to solve.
Kind regards,
MarkW