Neurofilament light polypeptide

NEFL
Identifiers
Aliases	NEFL, CMT1F, CMT2E, NF-L, NF68, NFL, PPP1R110, neurofilament, light polypeptide, neurofilament light, CMTDIG, neurofilament light chain
External IDs	OMIM: 162280; MGI: 97313; HomoloGene: 4487; GeneCards: NEFL; OMA:NEFL - orthologs
Gene location (Human)
Chr.	Chromosome 8 (human)
End	24,956,721 bp
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)
End	68,326,544 bp
RNA expression pattern
	Top expressed in
	spinal ganglia; ; pons; ; lateral nuclear group of thalamus; ; endothelial cell; ; superior vestibular nucleus; ; Brodmann area 23; ; orbitofrontal cortex; ; pars compacta; ; middle temporal gyrus; ; frontal pole;
	Top expressed in
	motor neuron; ; facial motor nucleus; ; anterior horn of spinal cord; ; deep cerebellar nuclei; ; superior cervical ganglion; ; medial vestibular nucleus; ; pontine nuclei; ; trigeminal ganglion; ; dorsal tegmental nucleus; ; substantia nigra;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	protein-macromolecule adaptor activity; structural molecule activity; structural constituent of cytoskeleton; protein C-terminus binding; protein binding; identical protein binding; protein heterodimerization activity; protein domain specific binding; phospholipase binding; structural constituent of postsynaptic intermediate filament cytoskeleton;
Cellular component	cytoplasm; cytosol; neurofilament; growth cone; myelin sheath; TSC1-TSC2 complex; axon; neuron projection; intermediate filament; axon cytoplasm; neuromuscular junction; Schaffer collateral - CA1 synapse; cholinergic synapse; postsynaptic intermediate filament cytoskeleton; presynaptic intermediate filament cytoskeleton;
Biological process	negative regulation of neuron apoptotic process; retrograde axonal transport; intermediate filament organization; response to sodium arsenite; neuron projection morphogenesis; protein polymerization; intermediate filament bundle assembly; neuromuscular process controlling balance; neurofilament bundle assembly; response to corticosterone; response to peptide hormone; response to organic substance; positive regulation of axonogenesis; MAPK cascade; anterograde axonal transport; axonal transport of mitochondrion; regulation of axon diameter; peripheral nervous system axon regeneration; locomotion; response to acrylamide; spinal cord development; cerebral cortex development; intermediate filament polymerization or depolymerization; neurofilament cytoskeleton organization; hippocampus development; response to toxic substance; microtubule cytoskeleton organization; axon development; synapse maturation; postsynaptic intermediate filament cytoskeleton organization; regulation of NMDA receptor activity;
	Sources:Amigo / QuickGO
Orthologs
	4747
	18039
	ENSG00000277586
	ENSMUSG00000022055
	P07196
	P08551
	NM_006158
	NM_010910
	NP_006149
	NP_035040
	Wikidata
View/Edit Human	View/Edit Mouse

Neurofilament light polypeptide (NFL), also known as neurofilament light chain, is a neurofilament protein that in humans 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 associated with Charcot–Marie–Tooth disease 1F and 2E.^[5]

Interactions

NFL has been shown to interact with:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000277586 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022055 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Miltenberger-Miltenyi G, Janecke AR, Wanschitz JV, Timmerman V, Windpassinger C, Auer-Grumbach M, Löscher WN (July 2007). "Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene". Archives of Neurology. 64 (7): 966–70. doi:10.1001/archneur.64.7.966. PMID 17620486.
^ "Entrez Gene: NEFL neurofilament, light polypeptide 68kDa".
^ 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 (October 2018). "Neurofilaments as biomarkers in neurological disorders" (PDF). Nature Reviews. Neurology. 14 (10): 577–589. doi:10.1038/s41582-018-0058-z. PMID 30171200. 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.
^ Thompson AB, Mead SH (December 2018). "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. 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.
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Zetterberg, Henrik (6 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.
^ Preische O, Schultz SA, Apel A, et al. (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.
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Frappier T, Stetzkowski-Marden F, Pradel LA (April 1991). "Interaction domains of neurofilament light chain and brain spectrin". The Biochemical Journal. 275 ( Pt 2) (2): 521–7. doi:10.1042/bj2750521. PMC 1150082. PMID 1902666.
^ Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y (April 1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". The Journal of Biological Chemistry. 271 (16): 9816–22. doi:10.1074/jbc.271.16.9816. PMID 8621664.
^ Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V (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): 44180–6. doi:10.1074/jbc.M207211200. PMID 12226091.

External links

Bird TD (26 March 2015). "Charcot-Marie-Tooth Neuropathy Type 1". In Pagon RA, Bird TD, Dolan CR, et al. (eds.). GeneReviews™ [Internet]. Seattle WA: University of Washington, Seattle. NBK1205. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
Bird, Thomas D (30 January 2014). Charcot-Marie-Tooth Neuropathy Type 2. PMID 20301462. NBK1285. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help) In GeneReviews
De Jonghe, Peter; Jordanova, Albena K (2011-10-27). Charcot-Marie-Tooth Neuropathy Type 2E/1F. NBK1187. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help) In GeneReviews

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000277586 – Ensembl, May 2017

[refGRCm38Ensembl-2] 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.

[pmid17620486-5] Miltenberger-Miltenyi G, Janecke AR, Wanschitz JV, Timmerman V, Windpassinger C, Auer-Grumbach M, Löscher WN (July 2007). "Clinical and electrophysiological features in Charcot-Marie-Tooth disease with mutations in the NEFL gene". Archives of Neurology. 64 (7): 966–70. doi:10.1001/archneur.64.7.966. PMID 17620486.

[entrez-6] "Entrez Gene: NEFL neurofilament, light polypeptide 68kDa".

[Neurofilament_biomarkers-7] 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 (October 2018). "Neurofilaments as biomarkers in neurological disorders" (PDF). Nature Reviews. Neurology. 14 (10): 577–589. doi:10.1038/s41582-018-0058-z. PMID 30171200. 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.

[Prion_neurodegeneration_biomarkers-8] Thompson AB, Mead SH (December 2018). "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. 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.

[ALS_systematic_review_and_meta-analysis-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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[MS_Meta-analysis-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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[11] Zetterberg, Henrik (6 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.

[12] Preische O, Schultz SA, Apel A, et al. (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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[pmid1902666-14] Frappier T, Stetzkowski-Marden F, Pradel LA (April 1991). "Interaction domains of neurofilament light chain and brain spectrin". The Biochemical Journal. 275 ( Pt 2) (2): 521–7. doi:10.1042/bj2750521. PMC 1150082. PMID 1902666.

[pmid8621664-15] Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, Sunakawa H, Ono Y (April 1996). "PKN associates and phosphorylates the head-rod domain of neurofilament protein". The Journal of Biological Chemistry. 271 (16): 9816–22. doi:10.1074/jbc.271.16.9816. PMID 8621664.

[pmid12226091-16] Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V (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): 44180–6. doi:10.1074/jbc.M207211200. PMID 12226091.

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Interactions

References

Further reading

External links