MTA and MS
Posted: Tue Feb 13, 2007 12:00 pm
Finally some researchers are starting to poke in the right direction, at least relative to my theory. Of course they are interpreting it in terms of immune system modulation. Just a shame they don't look at it from my view: as spermine synthase over-expression in the targeted brain cells following inactive X chromosome fragmentation. Spermine synthase is on the 2 X chromosomes in female cells but usually only one copy is expressed, from the active X.
Also, they are picking on those poor EAE rats again.
The first article is really old and all I can post is the title. The second article (abstract) is more recent.
Methylthioadenosine, a potent inhibitor of spermine synthase from bovine brain.
Pajula RL, Raina A. FEBS Lett. 1979 Mar 15;99(2):343-5.
Methylthioadenosine Reverses Brain Autoimmune Disease
Beatriz Moreno, PhD, Henar Hevia, PhD, Monica Santamaria, PhD, Jorge Sepulcre, MD, Javier Mun˜oz, BSc, Elena R. Garcı´a-Trevijano, PhD, Carmen Berasain, PhD, Fernando J. Corrales, PhD, Matias A. Avila, PhD, and Pablo Villoslada, MD
Objective: To assess the immunomodulatory activity of methylthioadenosine (MTA) in rodent experimental autoimmune encephalomyelitis (EAE) and in patients with multiple sclerosis.
Methods: We studied the effect of intraperitoneal MTA in the acute and chronic EAE model by quantifying clinical and histological scores and by performing immunohistochemistry stains of the brain. We studied the immunomodulatory effect of MTA in lymphocytes from EAE animals and in peripheral blood mononuclear cells from healthy control subjects and multiple sclerosis patients by assessing cell proliferation and cytokine gene expression, by real-time polymerase chain reaction, and by nuclear factor-κB modulation by Western blot.
Results: We found that MTA prevents acute EAE and, more importantly, reverses chronic-relapsing EAE. MTA treatment markedly inhibited brain inflammation and reduced brain damage. Administration of MTA suppressed T-cell activation in vivo and in vitro, likely through a blockade in T-cell signaling resulting in the prevention of inhibitor of kappa B (IκB-) degradation and in the impaired activation transcription factor nuclear factor-κB. Indeed, MTA suppressed the production of proinflammatory genes and cytokines (interferon-γ, tumor necrosis factor-, and inducible nitric oxide synthase) and increased the production of antiinflammatory cytokines (interleukin-10).
Interpretation: MTA has a remarkable immunomodulatory activity and may be beneficial for multiple sclerosis and other autoimmune diseases.
Ann Neurol 2006;60:323–334
Wesley
Also, they are picking on those poor EAE rats again.
The first article is really old and all I can post is the title. The second article (abstract) is more recent.
Methylthioadenosine, a potent inhibitor of spermine synthase from bovine brain.
Pajula RL, Raina A. FEBS Lett. 1979 Mar 15;99(2):343-5.
Methylthioadenosine Reverses Brain Autoimmune Disease
Beatriz Moreno, PhD, Henar Hevia, PhD, Monica Santamaria, PhD, Jorge Sepulcre, MD, Javier Mun˜oz, BSc, Elena R. Garcı´a-Trevijano, PhD, Carmen Berasain, PhD, Fernando J. Corrales, PhD, Matias A. Avila, PhD, and Pablo Villoslada, MD
Objective: To assess the immunomodulatory activity of methylthioadenosine (MTA) in rodent experimental autoimmune encephalomyelitis (EAE) and in patients with multiple sclerosis.
Methods: We studied the effect of intraperitoneal MTA in the acute and chronic EAE model by quantifying clinical and histological scores and by performing immunohistochemistry stains of the brain. We studied the immunomodulatory effect of MTA in lymphocytes from EAE animals and in peripheral blood mononuclear cells from healthy control subjects and multiple sclerosis patients by assessing cell proliferation and cytokine gene expression, by real-time polymerase chain reaction, and by nuclear factor-κB modulation by Western blot.
Results: We found that MTA prevents acute EAE and, more importantly, reverses chronic-relapsing EAE. MTA treatment markedly inhibited brain inflammation and reduced brain damage. Administration of MTA suppressed T-cell activation in vivo and in vitro, likely through a blockade in T-cell signaling resulting in the prevention of inhibitor of kappa B (IκB-) degradation and in the impaired activation transcription factor nuclear factor-κB. Indeed, MTA suppressed the production of proinflammatory genes and cytokines (interferon-γ, tumor necrosis factor-, and inducible nitric oxide synthase) and increased the production of antiinflammatory cytokines (interleukin-10).
Interpretation: MTA has a remarkable immunomodulatory activity and may be beneficial for multiple sclerosis and other autoimmune diseases.
Ann Neurol 2006;60:323–334
Wesley