Fressinaud C, Eyer J. Axoskeletal proteins prevent oligodendrocyte from toxic injury by upregulating survival, proliferation, and differentiation in vitro. Neurochem Int. 2012 Dec. doi:pii: S0197-0186(12)00410-X. 10.1016/j.neuint.2012.12.012.
Background: Neurofilaments (NF) are detected in the cerebrospinal fluid of MSers, and their concentration correlates with disease severity. These investigators have recently demonstrated that NF and co-isolated proteins increase the proliferation and differentiation of oligodendrocytes (OL) in the laboratory.
|Neurofilaments stained green within neuronal processes.|
“This study makes a lot of sense from a biological perspective i.e. proteins that are released from damage nerve cells then stimulate surrounding cells to repair the damage. In other words nature has built in signal for repair. What you may or may not know is that some MSers mount an immunological challenge to neurofilaments and make antibodies to the protein. Antibodies are responsible for mopping up proteins and targeting them to scavenger cells so that that can be cleared. MSers with with progressive disease tend to have higher levels of antibodies to neurofilament. I wonder if these antibodies are blocking the repair or recovery signals that neurofilaments provide to oligodendrocytes? This may be another mechanism underlying progressive MS.”
Eikelenboom et al. Multiple sclerosis: Neurofilament light chain antibodies are correlated to cerebral atrophy. Neurology. 2003 Jan 28;60(2):219-23.
OBJECTIVE: To evaluate markers of axonal damage in CSF and serum of MSers with different subtypes of MS in relation to measures of disease progression on MRI.
METHODS: In 51 MSers (21 relapsing-remitting, 20 secondary progressive, 10 primary progressive), levels of heavy and light neurofilaments (NfH and NfL) and antibodies to neurofilaments (anti-NfL and -NfH) as well as the total immunoglobulin G (IgG) were analyzed. MRI analysis included T2 hyperintense, T1 hypointense, and gadolinium enhancing lesions and markers of cerebral atrophy (ventricular and parenchymal fractions).
RESULTS: For the total group, correlations were found between the anti-NfL index and the parenchymal fraction (PF) (r = -0.51, p < 0.001), T2 lesion load (r = 0.41, p < 0.05), ventricular fraction (r = 0.37, p < 0.05), and T1 lesion load (r = 0.37, p < 0.05). For the anti-NfH index, a correlation was found with the PF (r = -0.39, p < 0.05). No correlations were found between the IgG index and MRI measures.
CONCLUSIONS: Intrathecal production of anti-NfL antibodies may serve as a marker of tissue damage, particularly axonal loss, in MS.
|Differing degrees of brain atrophy in a RRMSer (B) compared to an MSer with progressive disease (C). Could anti-NF antibodies be responsible for driving brain atrophy? Please note the healthy control on the left (A).|