neurofilament

Neurofilaments

Neurofilaments (NF) are the 10 nanometer or intermediate filaments found in neurons. They are a major component of the neuronal cytoskeleton, and are believed to function primarily to provide structural support for the axon and to regulate axon diameter. Neurofilaments are composed of polypeptide chains or subunits which belong to the same protein family as the intermediate filaments of other tissues such as keratin subunits, which make 10 nm filaments expressed specifically in epithelia. The family of proteins making intermediate filaments is divided into 5 major classes, the keratins forming the classes I and II. Class III contains the proteins vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP). The major neurofilament subunits occupy the class IV family of intermediate filaments, along with two other filament proteins of neurons, alpha-internexin and nestin.

The class IV intermediate filament genes all share two unique introns not found in other intermediate filament gene sequences, suggesting a common evolutionary origin from one primitive class IV gene. Finally, class V corresponds to intermediate filaments of the nuclear cytoskeleton, the nuclear lamins. The term neurofibril refers to a bundle of neurofilaments.

Neurofilament (NFL) has shown to be a promising biomarker of neuroaxonal injury in various neurological disorders but has not been investigated in Acute bacterial meningitis (ABM).

Grønhøj et al. aimed to obtain a temporal profile of NFL, neuron-specific enolase (NSE), and S100B in serum during ABM, and (ii) to evaluate their use as biomarkers of severity (Glasgow coma score) and prognosis (Glasgow Outcome Score, GOS and death) in severe ABM.

Fifteen adults with severe community-acquired ABM who were admitted to the intensive care unit (ICU) and fulfilled the inclusion criteria were included. Lumbar puncture and blood tests were performed on admission, and blood tests were performed three times daily during the ICU stay. GOS was obtained on day 30.

Serum NFL was significantly elevated in ABM patients compared to healthy controls, both at admission and throughout the observation period (p < .01). NFL increased significantly from day 1 up to day 3-6 (p < .0001), peaking day 6. NSE increased significantly from admission up to day 3 (p < .01). At day 5-6, the serum values were not significantly different from values at admission. The highest median serum value of S100B was observed at admission (0.10 µg/L, IQR 0.06-0.14), significantly decreasing day 4-6 (p < .05). None of the investigated biomarkers revealed significant correlation with severity and prognosis.

This study represents the first clinical observation of the temporal profile of NFL in serum, in severe ABM. No correlation with severity or prognosis 1).


Interest in neurofilaments has risen sharply in recent years with recognition of their potential as biomarkers of brain injury or neurodegeneration in CSF and blood. This is in the context of a growing appreciation for the complexity of the neurobiology of neurofilaments, new recognition of specialized roles for neurofilaments in synapses and a developing understanding of mechanisms responsible for their turnover.

Gafson et al. reviewed the neurobiology of neurofilament proteins, describing current understanding of their structure and function, including recently discovered evidence for their roles in synapses.

They explored the emerging understanding of the mechanisms of neurofilament degradation and clearance and review new methods for future elucidation of the kinetics of their turnover in humans. Primary roles of neurofilaments in the pathogenesis of human diseases will be described. With this background, they then will review critically evidence supporting use of neurofilament concentration measures as biomarkers of neuronal injury or degeneration. Finally, they will reflect on major challenges for studies of the neurobiology of intermediate filaments with specific attention to identifying what needs to be learned for more precise use and confident interpretation of neurofilament measures as biomarkers of neurodegeneration 2).


Khalil et al. in 2018 reviewed what is known about the structure and function of neurofilaments, discuss analytical aspects and knowledge of age-dependent normal ranges of neurofilaments and provide a comprehensive overview of studies on neurofilament light chain as a marker of axonal injury in different neurological disorders, including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson's disease. They also consider work needed to explore the value of this axonal damage marker in managing neurological diseases in daily practice 3).


1)
Grønhøj MH, Sejbaek T, Hansen RW, Larsen L, Dahl M, Schierbeck J, Poulsen FR. Serum levels of neurofilament light chain, neuron-specific enolase and S100 calcium-binding protein B during acute bacterial meningitis: a prospective cohort study. Infect Dis (Lond). 2021 Feb 13:1-11. doi: 10.1080/23744235.2021.1883730. Epub ahead of print. PMID: 33583314.
2)
Gafson AR, Barthélemy NR, Bomont P, Carare RO, Durham HD, Julien JP, Kuhle J, Leppert D, Nixon RA, Weller RO, Zetterberg H, Matthews PM. Neurofilaments: neurobiological foundations for biomarker applications. Brain. 2020 May 14. pii: awaa098. doi: 10.1093/brain/awaa098. [Epub ahead of print] PubMed PMID: 32408345.
3)
Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, Petzold A, Blennow K, Zetterberg H, Kuhle J. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018 Oct;14(10):577-589. doi: 10.1038/s41582-018-0058-z. Review. PubMed PMID: 30171200.
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