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Neurofilament light polypeptide

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(Redirected from NEFL (gene))

NEFL
Identifiers
AliasesNEFL, CMT1F, CMT2E, NF-L, NF68, NFL, PPP1R110, neurofilament, light polypeptide, neurofilament light, CMTDIG, neurofilament light chain
External IDsOMIM: 162280; MGI: 97313; HomoloGene: 4487; GeneCards: NEFL; OMA:NEFL - orthologs
Orthologs
SpeciesHumanMouse
Entrez

4747

18039

Ensembl

ENSG00000277586

ENSMUSG00000022055

UniProt

P07196

P08551

RefSeq (mRNA)

NM_006158

NM_010910

RefSeq (protein)

NP_006149

NP_035040

Location (UCSC)Chr 8: 24.95 – 24.96 MbChr 14: 68.32 – 68.33 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 10 nm 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.[5][6] 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.[7][8] It is a useful marker for disease monitoring in amyotrophic lateral sclerosis,[9] multiple sclerosis,[10] Alzheimer's disease,[11][12] and more recently Huntington's disease.[13] It is also promising marker for follow-up of patients with brain tumors.[14] 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.[15] 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.[16] Methods used in different studies for NfL measurement are sandwich enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence, and high-sensitive single molecule array (SIMOA).[17]

Neurofilament assembly and structure

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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.
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 other axons.

It is associated with Charcot–Marie–Tooth disease 1F and 2E.[5]

Interactions

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Neurofilament light polypeptide has been shown to interact with:

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000277586 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022055 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Miltenberger-Miltenyi G, Janecke AR, Wanschitz JV, Timmerman V, Windpassinger C, Auer-Grumbach M, et al. (July 2007). "Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene". Archives of Neurology. 64 (7): 966–970. doi:10.1001/archneur.64.7.966. PMID 17620486.
  6. ^ "Entrez Gene: NEFL neurofilament, light polypeptide 68kDa".
  7. ^ Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, et al. (October 2018). "Neurofilaments as biomarkers in neurological disorders". Nature Reviews. Neurology. 14 (10): 577–589. doi:10.1038/s41582-018-0058-z. PMID 30171200. S2CID 52140127. 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.
  8. ^ Thompson AG, Mead SH (June 2019). "Review: Fluid biomarkers in the human prion diseases". Molecular and Cellular Neurosciences. 97: 81–92. doi:10.1016/j.mcn.2018.12.003. PMID 30529227. S2CID 54437514. 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.
  9. ^ Xu Z, Henderson RD, David M, McCombe PA (2016). "Neurofilaments as Biomarkers for Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis". PLOS ONE. 11 (10): e0164625. Bibcode:2016PLoSO..1164625X. doi:10.1371/journal.pone.0164625. PMC 5061412. PMID 27732645. 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.
  10. ^ Cai L, Huang J (2018). "Neurofilament light chain as a biological marker for multiple sclerosis: a meta-analysis study". Neuropsychiatric Disease and Treatment. 14: 2241–2254. doi:10.2147/NDT.S173280. PMC 6126505. 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.
  11. ^ Zetterberg H, Schott JM (February 2019). "Biomarkers for Alzheimer's disease beyond amyloid and tau". Nature Medicine. 25 (2): 201–203. doi:10.1038/s41591-019-0348-z. PMID 30728536. S2CID 59607046.
  12. ^ Preische O, Schultz SA, Apel A, Kuhle J, Kaeser SA, Barro C, et al. (February 2019). "Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease". Nature Medicine. 25 (2): 277–283. doi:10.1038/s41591-018-0304-3. PMC 6367005. PMID 30664784.
  13. ^ Niemelä V, Landtblom AM, Blennow K, Sundblom J (27 February 2017). "Tau or neurofilament light-Which is the more suitable biomarker for Huntington's disease?". PLOS ONE. 12 (2): e0172762. Bibcode:2017PLoSO..1272762N. doi:10.1371/journal.pone.0172762. PMC 5328385. PMID 28241046.
  14. ^ Arslan B, Ayhan Arslan G, Tuncer A, Karabudak R, Sepici Dinçel A (April 2022). "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. doi:10.17305/bjbms.2021.7326. PMC 9519158. PMID 35490364. S2CID 248478048.
  15. ^ Kaeser SA, Lehallier B, Thinggaard M, Häsler LM, Apel A, Bergmann C, 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. S2CID 234008316. Retrieved February 11, 2021.
  16. ^ Shaw G, Madorsky I, Li Y, Wang Y, Jorgensen M, Rana S, et al. (2023-03-02). "Uman-type neurofilament light antibodies are effective reagents for the imaging of neurodegeneration". Brain Communications. 5 (2). doi:10.1093/braincomms/fcad067. ISSN 2632-1297. PMC 10120172. PMID 37091583.
  17. ^ Arslan B, Arslan GA, Tuncer A, Karabudak R, Dinçel AS (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". Bosnian Journal of Basic Medical Sciences. 22 (5): 699–706. doi:10.17305/bjbms.2021.7326. ISSN 2831-090X. PMC 9519158. PMID 35490364.
  18. ^ Frappier T, Stetzkowski-Marden F, Pradel LA (April 1991). "Interaction domains of neurofilament light chain and brain spectrin". The Biochemical Journal. 275 (2): 521–527. doi:10.1042/bj2750521. PMC 1150082. PMID 1902666.
  19. ^ Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, et al. (April 1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". The Journal of Biological Chemistry. 271 (16): 9816–9822. doi:10.1074/jbc.271.16.9816. PMID 8621664.
  20. ^ Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, et al. (November 2002). "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. doi:10.1074/jbc.M207211200. PMID 12226091.

Further reading

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