Neurofilament Proteins as Body Fluid Biomarkers of Neurodegeneration in Multiple Sclerosis

Abstract

Biomarkers of axonal degeneration have the potential to improve our capacity to predict and monitor neurological outcome in multiple sclerosis (MS) patients. Neurofilament proteins, one of the major proteins expressed within neurons and axons, have been detected in cerebrospinal fluid and blood samples from MS patients and are now being actively investigated for their utility as prognostic indicators of disease progression in MS. In this paper, we summarize the current literature on neurofilament structure, assembly, and degeneration and discuss their potential utility as biomarkers for monitoring neurological decline in MS. We also discuss the need to further develop sensitive methods for assaying neurofilaments in blood to improve clinical applicability.

Time-related morphometric studies of neurofilaments in brain contusions

“…Three kinds of proteins of different molecular weights form low-weight (NF-L), medium-weight (NF-M) and high-weight (NF-H) neurofilaments. Neurofilaments together with cyto keratins, lamins, vimentin and vimentin-like filaments constitute intermediate filaments which scaffold the nerve cell [6,26]. NF-L, NF-M and NF-H are uniformly dispersed in the perikaryon and processes both in the central and peripheral nervous systems [28].…”

“…NF-L, NF-M and NF-H are uniformly dispersed in the perikaryon and processes both in the central and peripheral nervous systems [28]. In the brain NF can be shown by means of immunohistochemical methods with labelled antibodies, in the cerebrospinal fluid with ELISA or Western-blotting [6,28]. Traumatic brain injuries (TBI) cause mechanical deformation of the nerve tissue, including the NF cytoskeleton, which may play a key role in the posttraumatic cessation of axonal transport [7].…”

Molecular Biomarkers in Multiple Sclerosis

“…One step in the right direction would be, that more researchers would appreciate the possibility to upload their -even though small-data sets with expression data and clinical data. This would enable researchers to utilize these data for [37] pNF-H (+) Cellular [93,94] plasma endothelial microparticles (+) miRNA [90] hsa-miR-1826 (+) hsa-miR-572 (+) hsa-miR-1979 (-) hsa-miR-614 (+) hsa-miR-22 (+) hsa-miR-648 (+) Serum and PBMC miRNA [25,90] hsa-miR-422a (+) PBMC miRNA [25][26][27]71,72,89] hsa-miR-19b (CD4+CD25+ cells) (+) hsa-miR-17-5p (+) hsa-miR-25 (CD4+CD25+ cells) (+) hsa-miR-18-5p (+) hsa-miR-1275 (+) hsa-miR-186-5p (-) hsa-miR-145-5p (+) hsa-miR-20a-5p (+) hsa-miR-491-5p (+) hsa-miR-20b-5p (+) hsa-miR-584-5p (+) hsa-miR-223-3p (+) hsa-miR-664-3p (+) hsa-miR-142-3p (+) mRNA [1] ATP7A ( Fas/FasL mRNA [5] ILT3 (-; mono.) miRNA [25,71,72] hsa-miR-18b (+) hsa-miR-599 (+) hsa-miR-96-5p (+; remission) Disease activity and treatment response…”

“…Due to this circumstance, many but not all antibodies, proteins and peptides that are found in the CSF can also be detected in serum, but, however, at different amounts and often physically altered due to modification and degradation processes in [29,37,38]. Markers that were found in CSF or brain tissue are summarized in Table 2.…”

“…Neurofilament subunits and fragments that are released during neuronal damages may even be processed in disease specific ways. However, neurofilament detection assays still have to be refined to increase sensitivity and specificity [6,37,50].…”