Biology:Neurofilament light polypeptide

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Neurofilament light polypeptide, also known as neurofilament light chain, abbreviated to NF-L or Nfl and with the HGNC name NEFL is a member of the intermediate filament protein family. This protein family consists of over 50 human proteins divided into 5 major classes, the Class I and II keratins, Class III vimentin, GFAP, desmin and the others, the Class IV neurofilaments and the Class V nuclear lamins. There are four major neurofilament subunits, NF-L, NF-M, NF-H and α-internexin. These form heteropolymers which assemble to produce 10nm neurofilaments which are only expressed in neurons where they are major structural proteins, particularly concentrated in large projection axons. Axons are particularly sensitive to mechanical and metabolic compromise and as a result axonal degeneration is a significant problem in many neurological disorders. The detection of neurofilament subunits in CSF and blood has therefore become widely used as a biomarker of ongoing axonal compromise. The NF-L protein is encoded by the NEFL gene.[1][2] Neurofilament light chain is a biomarker that can be measured with immunoassays in cerebrospinal fluid and plasma and reflects axonal damage in a wide variety of neurological disorders.[3][4] It is a useful marker for disease monitoring in amyotrophic lateral sclerosis,[5] multiple sclerosis,[6] Alzheimer's disease,[7][8] and more recently Huntington's disease.[9] It is also promising marker for follow-up of patients with brain tumors.[10] Higher levels of blood or CSF NF-L have been associated with increased mortality, as would be expected as release of this protein reflects ongoing axonal loss.[11] Recent work performed as a collaboration between EnCor Biotechnology Inc. and the University of Florida showed that the NF-L antibodies employed in the most widely used NF-L assays are specific for cleaved forms of NF-L generated by proteolysis induced by cell death.[12] Methods used in different studies for NfL measurement are sandwich enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence, and high-sensitive single molecule array (SIMOA).[13]

Neurofilament assembly and structure

Rat brain cells grown in tissue culture and stained, in green, with an antibody to neurofilament subunit NF-L, which reveals a large neuron. The culture was stained in red for α-internexin, which in this culture is found in neuronal stem cells surrounding the large neuron. Image courtesy of EnCor Biotechnology Inc.
A formalin fixed and paraffin embedded section of human cerebellum stained with an antibody to NF-L revealed with a brown dye, cell nuclei are revealed with a blue dye. Nuclear rich region at left is granular layer, region at right is molecular layer. The antibody binds processes of basket cells, parallel fiber axons, the perikarya of Purkinje cells and various othe axons. Image courtesy of EnCor Biotechnology Inc.

It is associated with Charcot–Marie–Tooth disease 1F and 2E.[1]

Interactions

Neurofilament light polypeptide has been shown to interact with:

References

  1. ↑ 1.0 1.1 "Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene". Archives of Neurology 64 (7): 966–970. July 2007. doi:10.1001/archneur.64.7.966. PMID 17620486. 
  2. ↑ "Entrez Gene: NEFL neurofilament, light polypeptide 68kDa". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4747. 
  3. ↑ "Neurofilaments as biomarkers in neurological disorders". Nature Reviews. Neurology 14 (10): 577–589. October 2018. doi:10.1038/s41582-018-0058-z. PMID 30171200. https://discovery.ucl.ac.uk/id/eprint/10057189/. "neuroaxonal damage is the pathological substrate of permanent disability in various neurological disorders. ... Here, we review 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 disease.". 
  4. ↑ "Review: Fluid biomarkers in the human prion diseases". Molecular and Cellular Neurosciences 97: 81–92. June 2019. doi:10.1016/j.mcn.2018.12.003. PMID 30529227. https://discovery.ucl.ac.uk/id/eprint/10064537/. "The very rapid neurodegeneration of prion disease results in strong signals from surrogate protein markers in the blood that reflect neuronal, axonal, synaptic or glial pathology in the brain: notably the tau and neurofilament light chain proteins.". 
  5. ↑ "Neurofilaments as Biomarkers for Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis". PLOS ONE 11 (10): e0164625. 2016. doi:10.1371/journal.pone.0164625. PMID 27732645. Bibcode: 2016PLoSO..1164625X. "NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression.". 
  6. ↑ "Neurofilament light chain as a biological marker for multiple sclerosis: a meta-analysis study". Neuropsychiatric Disease and Treatment 14: 2241–2254. 2018. doi:10.2147/NDT.S173280. PMID 30214214. "NFL chain has significantly increased in MS patients, which substantially strengthens the clinical evidence of the NFL in MS. The NFL may be used as a prognostic biomarker to monitor disease progression, disease activity, and treatment efficacy in the future.". 
  7. ↑ "Biomarkers for Alzheimer's disease beyond amyloid and tau". Nature Medicine 25 (2): 201–203. February 2019. doi:10.1038/s41591-019-0348-z. PMID 30728536. https://discovery.ucl.ac.uk/id/eprint/10069672/. 
  8. ↑ "Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease". Nature Medicine 25 (2): 277–283. February 2019. doi:10.1038/s41591-018-0304-3. PMID 30664784. 
  9. ↑ "Tau or neurofilament light-Which is the more suitable biomarker for Huntington's disease?". PLOS ONE 12 (2): e0172762. 27 February 2017. doi:10.1371/journal.pone.0172762. PMID 28241046. Bibcode: 2017PLoSO..1272762N. 
  10. ↑ "Evaluation of cerebrospinal fluid neurofilament light chain levels in multiple sclerosis and non-demyelinating diseases of the central nervous system: clinical and biochemical perspective". Bosnian Journal of Basic Medical Sciences 22 (5): 699–706. April 2022. doi:10.17305/bjbms.2021.7326. PMID 35490364. 
  11. ↑ Kaeser, Stephan A.; Lehallier, Benoit; Thinggaard, Mikael; Häsler, Lisa M.; Apel, Anja; Bergmann, Carina; Berdnik, Daniela; Jeune, Bernard et al. (2021). "A neuronal blood marker is associated with mortality in old age". Nature Aging 1 (2): 218–225. doi:10.1038/s43587-021-00028-4. PMID 37118632. https://www.nature.com/articles/s43587-021-00028-4. Retrieved February 11, 2021. 
  12. ↑ Template:Cite braincomms
  13. ↑ Arslan, Burak; Arslan, Gökçe Ayhan; Tuncer, Aslı; Karabudak, Rana; Dinçel, Aylin Sepici (2022-09-16). "Evaluation of cerebrospinal fluid neurofilament light chain levels in multiple sclerosis and non-demyelinating diseases of the central nervous system: clinical and biochemical perspective" (in en). Bosnian Journal of Basic Medical Sciences 22 (5): 699–706. doi:10.17305/bjbms.2021.7326. ISSN 2831-090X. PMID 35490364. PMC 9519158. https://www.bjbms.org/ojs/index.php/bjbms/article/view/7326. 
  14. ↑ "Interaction domains of neurofilament light chain and brain spectrin". The Biochemical Journal 275 (2): 521–527. April 1991. doi:10.1042/bj2750521. PMID 1902666. 
  15. ↑ "PKN associates and phosphorylates the head-rod domain of neurofilament protein". The Journal of Biological Chemistry 271 (16): 9816–9822. April 1996. doi:10.1074/jbc.271.16.9816. PMID 8621664. 
  16. ↑ "The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton". The Journal of Biological Chemistry 277 (46): 44180–44186. November 2002. doi:10.1074/jbc.M207211200. PMID 12226091. 

Further reading

External links



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