A study on the mechanisms of neurodegeneration for Multiple Sclerosis caught our attention.
We just published a post on Progressive Multiple Sclerosis , and the approach of the study published in the Dovepress Journal , is a noteworthy additional path to understand Neurodegeneration of the Central Nervous System (CNS).
Essentially, the research studied an infection by the T-lymphotropic virus (hnRNP A1), which causes an infection of the spinal cord. During that infection the immune system manufactured antibodies against the virus.
The study showed that those antibodies ”… caused neurodegeneration in neuronal cell lines...Further, microarray analyses of neurons exposed to anti-hnRNP A1 antibodies revealed novel pathways of neurodegeneration related to alterations of RNA levels of the spinal paraplegia genes (SPGs)…What is interesting is that the hnRNP A1 infection is similar clinically, pathologically, and immunologically to progressive MS, so the authors took it as an MS model…”
So here you would have it: The antibodies generated in response to the viral infection would in turn, cause havoc in the Central Nervous System!
Assuming all forms of MS neurodegeneration are virus antibody related could be a stretch. However, this plays well in the assumption that MS would be triggered by a virus such as Epstein-Barr’s, and/or others 
But why would antibodies, which are markers for T-Cell immune system attack, trigger neurodegeneration? That is still unknown :
“…The cause of neurodegeneration is largely unknown. One candidate molecule that could cause neurodegeneration is antibody…”
Interestingly, specific antibodies are used as treatments to combat Alzheimer’s neurodegeneration. But the processes here are completely different:
The amyloid beta plaques, hallmark of the disease, are targeted and attacked by antibodies.
“…The antibody was then able to bind itself to the deposited amyloid beta, and clear roughly 50 percent of pre-existing plaques in the mice without causing damage to tiny vessels in the brain……Lilly’s best known Alzheimer’s disease drug is solanezumab, a medicine given by infusion that attacks amyloid beta protein. In data presented in August, the drug failed in large clinical trials to arrest cognitive and physical declines among patients with mild to moderate Alzheimer’s. But it was shown to somewhat delay cognitive declines in patients with mild symptoms…”
By the way, this means that attacking the amyloid beta protein plaque is no guarantee to arrest the Alzheimer’s dementia symptoms.
The topic of antibody therapy against neurodegenerative diseases is further discussed in a Caltech article .The concept is the same: “…[therapy is based on ] Antibodies that can recognize and remove misfolded proteins…”
In order to understand how antibodies could be involved in either attacking the CNS or helping heal it, we have to understand how antibodies work. Here is Wikipedia’s definition:
“…An antibody (Ab), also known as an immunoglobulin (Ig), is a large Y-shaped protein produced by B-cells that is used by the immune system to identify and neutralize foreign objects…”
In a nutshell, an antibody flags an object (bacteria, virus, or other substance) for attack by the immune system.
In the case of Alzheimer’s brain amyloid plaque, the goal is to flag the plaque for attack.
The case of the MS causing virus has a very different process, here the antibodies generated against the virus can have the nasty side effect of reducing the neuronal firing .
- The antibody antigen lockup (Fvasconcellos, Wikipedia Commons))
Such detrimental activities of antibodies is at the core of “pure” autoimmune diseases, but here the antibodies are dubbed auto-antibodies because they flag bonified components of people’s bodies, as opposed to foreign pathogens.
In Myasthenia Gravis (MG), for example, antibodies react to muscle proteins titin, ryanodine calcium channel receptor (RyR), and Kv1.4 potassium channels (cardiac electrical control). (Wikipedia on Myasthenia Gravis, and .
(MG is a neuromuscular disorders involve the muscles and the nerves that control them.)
The MS study was about viral antibodies indirectly affecting the firing of the Central Nervous System, as in MG, we are closer to the narrow definition of autoimmunity where the body generates antibodies to itself.
This is why, in most articles on MS, authors will say that MS is “thought” of as an auto-immune disease, although certain auto-antibodies been associated with MS by a study published in the New England Journal Of Medicine  , it seems more a correlation than an outright causation.
So, is MS’s neurodegeneration caused by an inflammatory reaction of the body to viruses? Maybe, but it could be one cause out of several.
Just look at this quote from :
“…Several possibilities exist for the relationship between inflammation and neurodegeneration: (1) that inflammation induces neurodegeneration; (2) that neurodegeneration causes inflammation; (3) other factors contribute to the development of inflammation and/or neurodegeneration; (4) inflammation and neurodegeneration participate in a cycle or a cascade in which they augment one another; and (5) that inflammation can protect against neurodegeneration. In the context of MS and its animal models these hypotheses are not necessarily mutually exclusive.”
The mess is still messy! To be continued….
Talk to your Doctor
medinewsdigest ; ‘IN DEPTH: Review Of 2012 Research On Progressive Multiple Sclerosis’ ; Dec 2012
Dovepress Journal; “”Pathogenic mechanisms of neurodegeneration based on the phenotypic expression of progressive forms of immune-mediated neurologic disease” ; Sep 2012
Journal of Neuro-Immunology , “Inflammation, Demyelination, Neurodegeneration and Neuroprotection in the Pathogenesis of Multiple Sclerosis” ; March 2077
Reuters ; “Lilly tests therapy to rid brain plaques in mice with Alzheimer’s”; Dec 2012
Caltech ; Reviews in the Neurosciences ; “Antibody therapy in Neurodegenerative Disease” ; 2010
Hindawi ; “Three Types of Striational Antibodies in Myasthenia Gravis” ;2011
Pubmed ; “Myasthenia gravis” ;June 2011
NEJM ; “Antimyelin Antibodies as a Predictor of Clinically Definite Multiple Sclerosis after a First Demyelinating Event” ; 2003