Editing Neurofilament

{{Short description|Type IV intermediate filaments found in the cytoplasm of neurons}}
{{infobox protein
| Name = [[NEFL|NF-L]] low molecular weight neurofilament protein
| caption = 
| image = 
| width = 
| HGNCid = 7739
| Symbol = [[NEFL]]
| AltSymbols = 
| EntrezGene = 4747
| OMIM = 162280
| RefSeq = NM_006158
| UniProt = P07196
| PDB = 
| ECnumber = 
| Chromosome = 8
| Arm = p
| Band = 21
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[NEFM|NF-M]] medium molecular weight neurofilament protein
| caption = 
| image = 
| width = 
| HGNCid = 7734
| Symbol = NEFM
| AltSymbols = NEF3
| EntrezGene = 4741
| OMIM = 162250
| RefSeq = NM_005382
| UniProt = P07197
| PDB = 
| ECnumber = 
| Chromosome = 8
| Arm = p
| Band = 21
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[NEFH|NF-H]] high molecular weight neurofilament protein
| caption = 
| image = 
| width = 
| HGNCid = 7737
| Symbol = NEFH
| AltSymbols = 
| EntrezGene = 4744
| OMIM = 162230
| RefSeq = NM_021076
| UniProt = P12036
| PDB = 
| ECnumber = 
| Chromosome = 22
| Arm = q
| Band = 12.1
| LocusSupplementaryData = -13.1
}}
{{infobox protein
| Name = [[Internexin|Alpha-internexin]] neuronal intermediate filament protein
| caption = 
| image = 
| width = 
| HGNCid = 6057
| Symbol = INA
| AltSymbols = NEF5
| EntrezGene = 9118
| OMIM = 605338
| RefSeq = NM_032727
| UniProt = Q5SYD2
| PDB = 
| ECnumber = 
| Chromosome = 10
| Arm = q
| Band = 24
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = Peripherin neuronal intermediate filament protein
| caption = 
| image = 
| width = 
| HGNCid = 9461
| Symbol = PRPH
| AltSymbols =NEF4 
| EntrezGene = 5630
| OMIM = 170710
| RefSeq = NM_006262.3
| UniProt = P41219
| PDB = 
| ECnumber = 
| Chromosome = 12
| Arm = q
| Band = 13.12
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = Nestin neuronal stem cell intermediate filament protein
| caption = 
| image = 
| width = 
| HGNCid = 7756
| Symbol = NES
| AltSymbols =
| EntrezGene = 10763
| OMIM = 600915
| RefSeq = NP_006608
| UniProt = P48681
| PDB = 
| ECnumber =
| Chromosome = 1
| Arm = q
| Band = 23.1
| LocusSupplementaryData = 
}}

'''Neurofilaments''' ('''NF''') are classed as [[Intermediate filament#Type IV|type IV intermediate filaments]] found in the [[cytoplasm]] of [[neurons]]. They are protein polymers measuring 10&nbsp;nm in diameter and many micrometers in length.<ref name="Yuan">{{cite journal |last1=Yuan |first1=A |last2=Rao |first2=MV |last3=Veeranna |last4=Nixon |first4=RA |title=Neurofilaments at a glance. |journal=Journal of Cell Science |date=15 July 2012 |volume=125 |issue=Pt 14 |pages=3257–63 |doi=10.1242/jcs.104729 |pmid=22956720|pmc=3516374 }}</ref>  Together with [[microtubule]]s (~25&nbsp;nm) and [[microfilament]]s (7&nbsp;nm), they form the neuronal [[cytoskeleton]]. They are believed to function primarily to provide structural support for [[axon]]s and to regulate axon diameter, which influences [[nerve conduction velocity]].  The proteins that form neurofilaments are members of the intermediate filament protein family, which is divided into six types based on their gene organization and protein structure.  Types I and II are the [[keratin]]s which are expressed in epithelia. Type III contains the proteins [[vimentin]], [[desmin]], [[peripherin]] and [[glial fibrillary acidic protein]] (GFAP). Type IV consists of the neurofilament proteins NF-L, NF-M, NF-H and [[internexin | α-internexin]]. Type V consists of the [[Lamin|nuclear lamins]], and type VI consists of the protein [[Nestin (protein)|nestin]]. The type 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 type IV gene.

Any proteinaceous filament that extends in the cytoplasm of a nerve cell is also termed a ''neurofibril''.<ref name="MW">{{cite web |title=Definition of Neurofibril |url=https://www.merriam-webster.com/dictionary/neurofibril |website=www.merriam-webster.com |access-date=6 December 2019 |language=en}}</ref> This name is used in the [[neurofibrillary tangle]]s of some [[neurodegenerative disease]]s.

==Neurofilament proteins==
The protein composition of neurofilaments varies widely across different animal phyla. Most is known about mammalian neurofilaments.  Historically, mammalian neurofilaments were originally thought to be composed of just three proteins called neurofilament protein NF-L (low molecular weight; [[NEFL|NF-L]]), NF-M (medium molecular weight; [[NEFM|NF-M]]) and NF-H (high molecular weight; [[NEFH|NF-H]]).  These proteins were discovered from studies of [[axonal transport]] and are often referred to as the "neurofilament triplet".<ref name=":0">{{cite journal | vauthors = Hoffman PN, Lasek RJ | title = The slow component of axonal transport. Identification of major structural polypeptides of the axon and their generality among mammalian neurons | journal = The Journal of Cell Biology | volume = 66 | issue = 2 | pages = 351–66 | date = August 1975 | pmid = 49355 | pmc = 2109569 | doi = 10.1083/jcb.66.2.351 }}</ref>  However, it is now clear that neurofilaments also contain the protein α-internexin<ref>{{cite journal | vauthors = Yuan A, Rao MV, Sasaki T, Chen Y, Kumar A, Liem RK, Eyer J, Peterson AC, Julien JP, Nixon RA | display-authors = 6 | title = α-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS | journal = The Journal of Neuroscience | volume = 26 | issue = 39 | pages = 10006–19 | date = September 2006 | pmid = 17005864 | pmc = 6674481 | doi = 10.1523/jneurosci.2580-06.2006 }}</ref> and that neurofilaments in the peripheral nervous system can also contain the protein peripherin.<ref>{{cite journal | vauthors = Yuan A, Sasaki T, Kumar A, Peterhoff CM, Rao MV, Liem RK, Julien JP, Nixon RA | display-authors = 6 | title = Peripherin is a subunit of peripheral nerve neurofilaments: implications for differential vulnerability of CNS and peripheral nervous system axons | journal = The Journal of Neuroscience | volume = 32 | issue = 25 | pages = 8501–8 | date = June 2012 | pmid = 22723690 | pmc = 3405552 | doi = 10.1523/jneurosci.1081-12.2012 }}</ref> (this is different from [[peripherin 2]] that is expressed in the [[retina]]). Thus mammalian neurofilaments are heteropolymers of up to five different proteins: NF-L, NF-M, NF-H, α-internexin and peripherin. The five neurofilament proteins can co-assemble in different combinations in different nerve cell types and at different stages of development. The precise composition of neurofilaments in any given nerve cell depends on the relative expression levels of the neurofilament proteins in the cell at that time.  For example, NF-H expression is low in developing neurons and increases postnatally in neurons with myelinated axons.<ref>{{cite journal | vauthors = Nixon RA, Shea TB | title = Dynamics of neuronal intermediate filaments: a developmental perspective | journal = Cell Motility and the Cytoskeleton | volume = 22 | issue = 2 | pages = 81–91 | year = 1992 | pmid = 1633625 | doi = 10.1002/cm.970220202 | doi-access = free }}</ref>  In the adult nervous system neurofilaments in small unmyelinated axons contain more peripherin and less NF-H whereas neurofilaments in large myelinated axons contain more NF-H and less peripherin. The type III intermediate filament subunit, [[vimentin]], is expressed in developing neurons and a few very unusual neurons in the adult in association with type IV proteins, such as the [[horizontal neurons]] of the [[retina]].
{| class="wikitable"
|+Human neurofilament subunit proteins
!Protein
!Amino acids
!NCBI Ref Seq
!Predicted molecular mass
!Apparent molecular mass (SDS-PAGE)
|-
|Peripherin
|470
|NP_006253.2
|53.7 kDa
|~56 kDa
|-
|α-Internexin
|499
|NP_116116.1
|55.4 kDa
|~66 kDa
|-
|Neurofilament protein L
|543
|NP_006149.2
|61.5 kDa
|~70 kDa
|-
|Neurofilament protein M
|916
|NP_005373.2
|102.5 kDa
|~160 kDa
|-
|Neurofilament protein H
|1020
|NP_066554.2
|111.9 kDA
|~200 kDa
|}
The triplet proteins are named based upon their relative size (low, medium, high).  The apparent [[molecular mass]] of each protein determined by [[SDS-PAGE]] is greater than the mass predicted from the amino sequence.  This is due to the anomalous electrophoretic migration of these proteins and is particularly extreme for neurofilament proteins NF-M and NF-H due to their high content of charged amino acids and extensive phosphorylation.  All three neurofilament triplet proteins contain long stretches of polypeptide sequence rich in [[glutamic acid]] and [[lysine]] residues, and NF-M and especially NF-H also contain multiple tandemly repeated [[serine]] phosphorylation sites. These sites almost all contain the peptide lysine-serine-proline (KSP), and phosphorylation is normally found on axonal and not dendritic neurofilaments. Human NF-M has 13 of these KSP sites, while human NF-H is expressed from two [[allele]]s one of which produces 44 and the other 45 KSP repeats.

== Neurofilament assembly and structure ==
[[File:Neuron in tissue culture.jpg|thumb|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.]]

[[File:MCA-6H112 NFL 4K citra HuCbl 20X 02-wiki.jpg|thumb|A formalin fixed and paraffin embedded section of human [[cerebellum]] stained with an antibody to neurofilament light, 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 cell|Purkinje]] cells and various other axons.]]

Like other intermediate filament proteins, the neurofilament proteins all share a common central [[Alpha helix|alpha helical]] region, known as the rod domain because of its rod-like tertiary structure, flanked by [[N-terminus|amino terminal]] and [[C-terminus|carboxy terminal]] domains that are largely unstructured.  The rod domains of two neurofilament proteins dimerize to form an alpha-helical [[coiled coil]].  Two dimers associate in a staggered antiparallel manner to form a tetramer.  This tetramer is believed to be the basic subunit (i.e. building block) of the neurofilament.  Tetramer subunits associate side-to-side to form unit-length filaments, which then anneal end-to-end to form the mature neurofilament polymer, but the precise organization of these subunits within the polymer is not known, largely because of the heterogeneous protein composition and the inability to crystallize neurofilaments or neurofilament proteins.  Structural models generally assume eight tetramers (32 neurofilament polypeptides) in a filament cross-section, but measurements of linear mass density suggest that this can vary.

The amino terminal domains of the neurofilament proteins contain numerous phosphorylation sites and appear to be important for subunit interactions during filament assembly.  The carboxy terminal domains appear to be intrinsically disordered domains that lack alpha helix or beta sheet.  The different sizes of the neurofilament proteins are largely due to differences in the length of the carboxy terminal domains.  These domains are rich in acidic and basic amino acid residues.  The carboxy terminal domains of NF-M and NF-H are the longest and are modified extensively by post-translational modifications such as [[phosphorylation]] and [[glycosylation]] in vivo.  They project radially from the filament backbone to form a dense brush border of highly charged and unstructured domains analogous to the bristles on a bottle brush.  These entropically flailing domains have been proposed to define a zone of exclusion around each filament, effectively spacing the filaments apart from their neighbors.  In this way, the carboxy terminal projections maximize the space-filling properties of the neurofilament polymers.  By electron microscopy, these domains appear as projections called sidearms that appear to contact neighboring filaments.[[File:Mouse NT antibody NF Ki67.jpg|thumb|[[Antibody]] [[staining|stain]] against neurofilament (green) and [[Ki-67 (protein)|Ki 67]] (red) in a mouse [[embryo]] 12.5 days after [[fertilization]]. The cells expressing neurofilaments are in the [[dorsal root ganglia]] shown in green while [[cell growth|proliferating cells]] are in the [[ventricular system|ventricular zone]] in the [[neural tube]] and colored red.]]

== Neurofilament function ==
[[File:Central chromatolysis - nf - high mag.jpg|thumb|right|[[Micrograph]] of [[white matter]] (bottom of image) and the [[anterior horn of spinal cord|anterior horn of the spinal cord]] showing [[motor neuron]]s with [[central chromatolysis]]. Neurofilament [[Immunostaining|immunostain]].]]
Neurofilaments are found in [[vertebrate]] neurons in especially high concentrations in axons, where they are all aligned in parallel along the long axis of the axon forming a continuously overlapping array.  They have been proposed to function as space-filling structures that increase axonal diameter.  Their contribution to axon diameter is determined by the number of neurofilaments in the axon and their packing density. The number of neurofilaments in the axon is thought to be determined by neurofilament gene expression<ref>{{cite book |title=Molecular biology of the cell |year=2002 |url=https://archive.org/details/molecularbiolog000wils |url-access=registration |publisher=Garland Science |isbn=978-0-8153-3218-3 |edition=4th}}</ref> and axonal transport.  The packing density of the filaments is determined by their side-arms which define the spacing between neighboring filaments.  Phosphorylation of the sidearms is thought to increase their extensibility, increasing the spacing between neighboring filaments<ref>{{cite journal | vauthors = Eyer J, Leterrier JF | title = Influence of the phosphorylation state of neurofilament proteins on the interactions between purified filaments in vitro | journal = The Biochemical Journal | volume = 252 | issue = 3 | pages = 655–60 | date = June 1988 | pmid = 2844152 | pmc = 1149198 | doi = 10.1042/bj2520655 }}</ref> by the binding of divalent cations between the sidearms of adjacent filaments<ref>{{cite journal | vauthors = Kushkuley J, Chan WK, Lee S, Eyer J, Leterrier JF, Letournel F, Shea TB | title = Neurofilament cross-bridging competes with kinesin-dependent association of neurofilaments with microtubules | journal = Journal of Cell Science | volume = 122 | issue = Pt 19 | pages = 3579–86 | date = October 2009 | pmid = 19737816 | doi = 10.1242/jcs.051318 | s2cid = 5883157 | doi-access =  }}</ref><ref>{{cite journal | vauthors = Kushkuley J, Metkar S, Chan WK, Lee S, Shea TB | title = Aluminum induces neurofilament aggregation by stabilizing cross-bridging of phosphorylated c-terminal sidearms | journal = Brain Research | volume = 1322 | pages = 118–23 | date = March 2010 | pmid = 20132798 | doi = 10.1016/j.brainres.2010.01.075 | s2cid = 9615612 }}</ref>

Early in development, axons are narrow processes that contain relatively few neurofilaments.  Those axons that become myelinated accumulate more neurofilaments, which drives the expansion of their caliber.  After an axon has grown and connected with its [[target cell]], the diameter of the axon may increase as much as fivefold.<ref name="MBC">{{cite book |last1=Alberts |first1=D |title=Molecular biology of the cell |date=2015 |isbn=9780815344643 |page=947 |edition=Sixth}}</ref>  This is caused by an increase in the number of neurofilaments exported from the nerve cell body as well as a slowing of their rate of transport.  In mature myelinated axons, neurofilaments can be the single most abundant cytoplasmic structure and can occupy most of the axonal cross-sectional area.  For example, a large myelinated axon may contain thousands of neurofilaments in one cross-section

== Neurofilament transport ==
In addition to their structural role in axons, neurofilaments are also cargoes of [[axonal transport]].<ref name=":0" />  Most of the neurofilament proteins in axons are synthesized in the nerve cell body, where they rapidly assemble into neurofilament polymers within about 30 minutes.<ref>{{cite journal | vauthors = Black MM, Keyser P, Sobel E | title = Interval between the synthesis and assembly of cytoskeletal proteins in cultured neurons | journal = The Journal of Neuroscience | volume = 6 | issue = 4 | pages = 1004–12 | date = April 1986 | pmid = 3084715 | pmc = 6568432 | doi = 10.1523/JNEUROSCI.06-04-01004.1986 }}</ref>  These assembled neurofilament polymers are transported along the axon on [[microtubule]] tracks powered by microtubule [[motor protein]]s.<ref>{{cite journal | vauthors = Wang L, Ho CL, Sun D, Liem RK, Brown A | title = Rapid movement of axonal neurofilaments interrupted by prolonged pauses | journal = Nature Cell Biology | volume = 2 | issue = 3 | pages = 137–41 | date = March 2000 | pmid = 10707083 | doi = 10.1038/35004008 | s2cid = 41152820 }}</ref>   The filaments move bidirectionally, i.e. both towards the axon tip (anterograde) and towards the cell body (retrograde), but the net direction is anterograde.  The filaments move at velocities of up to 8&nbsp;μm/s on short time scales (seconds or minutes), with average velocities of approximately 1&nbsp;μm/s.<ref>{{cite journal | vauthors = Fenn JD, Johnson CM, Peng J, Jung P, Brown A | title = Kymograph analysis with high temporal resolution reveals new features of neurofilament transport kinetics | journal = Cytoskeleton | volume = 75 | issue = 1 | pages = 22–41 | date = January 2018 | pmid = 28926211 | pmc = 6005378 | doi = 10.1002/cm.21411 }}</ref> However, the average velocity on longer time scales (hours or days) is slow because the movements are very infrequent, consisting of brief sprints interrupted by long pauses.<ref>{{cite journal | vauthors = Brown A | title = Slow axonal transport: stop and go traffic in the axon | journal = Nature Reviews. Molecular Cell Biology | volume = 1 | issue = 2 | pages = 153–6 | date = November 2000 | pmid = 11253369 | doi = 10.1038/35040102 | s2cid = 205010517 }}</ref><ref>{{cite journal | vauthors = Brown A, Wang L, Jung P | title = Stochastic simulation of neurofilament transport in axons: the "stop-and-go" hypothesis | journal = Molecular Biology of the Cell | volume = 16 | issue = 9 | pages = 4243–55 | date = September 2005 | pmid = 16000374 | pmc = 1196334 | doi = 10.1091/mbc.E05-02-0141 }}</ref>  Thus on long time scales neurofilaments move in the slow component of axonal transport.

== Clinical and research applications ==
{{Further|Neurofibrillary tangle}}
Numerous specific [[antibodies]] to neurofilament proteins have been developed and are commercially available.  These antibodies can be used to detect neurofilament proteins in cells and tissues using [[immunofluorescence]] microscopy or [[immunohistochemistry]].  Such antibodies are widely used to identify neurons and their processes in [[histological section]]s and in [[tissue culture]]. The type VI intermediate filament protein Nestin is expressed in developing neurons and glia.  Nestin is considered a marker of neuronal stem cells, and the presence of this protein is widely used to define [[neurogenesis]]. This protein is lost as development proceeds.

Neurofilament antibodies are also commonly used in diagnostic [[neuropathology]].  Staining with these antibodies can distinguish neurons (positive for neurofilament proteins) from [[glia]] (negative for neurofilament proteins).

There is also considerable clinical interest in the use of neurofilament proteins as [[biomarker]]s of axonal damage in diseases affecting the central nervous system.<ref>{{cite journal | vauthors = Petzold A | title = Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss | journal = Journal of the Neurological Sciences | volume = 233 | issue = 1–2 | pages = 183–98 | date = June 2005 | pmid = 15896809 | doi = 10.1016/j.jns.2005.03.015 | s2cid = 18311152 | url = http://discovery.ucl.ac.uk/18928/1/18928.pdf }}</ref><ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Neurofilaments as biomarkers in neurological disorders | journal = Nature Reviews. Neurology | volume = 14 | issue = 10 | pages = 577–589 | date = October 2018 | pmid = 30171200 | doi = 10.1038/s41582-018-0058-z | s2cid = 52140127 | url = https://discovery.ucl.ac.uk/id/eprint/10057189/1/Petzold_Horne_Fig1%20DLD-18-450.pdf }}</ref>  When neurons or axons degenerate, neurofilament proteins are released into the blood or cerebrospinal fluid.  Immunoassays of neurofilament proteins in cerebrospinal fluid and plasma can thus serve as indicators of axonal damage in neurological disorders.<ref>{{cite journal | vauthors = Jonsson M, Zetterberg H, van Straaten E, Lind K, Syversen S, Edman A, Blennow K, Rosengren L, Pantoni L, Inzitari D, Wallin A | display-authors = 6 | title = Cerebrospinal fluid biomarkers of white matter lesions - cross-sectional results from the LADIS study | journal = European Journal of Neurology | volume = 17 | issue = 3 | pages = 377–82 | date = March 2010 | pmid = 19845747 | doi = 10.1111/j.1468-1331.2009.02808.x | s2cid = 31052853 }}</ref>  NF-L levels in blood and CSF are therefore useful markers for disease monitoring in [[amyotrophic lateral sclerosis]],<ref>{{cite journal | vauthors = Rosengren LE, Karlsson JE, Karlsson JO, Persson LI, Wikkelsø C | title = Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF | journal = Journal of Neurochemistry | volume = 67 | issue = 5 | pages = 2013–8 | date = November 1996 | pmid = 8863508 | doi = 10.1046/j.1471-4159.1996.67052013.x | s2cid = 36897027 }}</ref> [[multiple sclerosis]],<ref>{{cite journal | vauthors = Teunissen CE, Iacobaeus E, Khademi M, Brundin L, Norgren N, Koel-Simmelink MJ, Schepens M, Bouwman F, Twaalfhoven HA, Blom HJ, Jakobs C, Dijkstra CD | display-authors = 6 | title = Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis | journal = Neurology | volume = 72 | issue = 15 | pages = 1322–9 | date = April 2009 | pmid = 19365053 | doi = 10.1212/wnl.0b013e3181a0fe3f | s2cid = 22681349 }},</ref> spinal muscular atrophy, and more recently [[Huntington's disease]].<ref>{{cite journal | vauthors = Niemelä V, Landtblom AM, Blennow K, Sundblom J | title = Tau or neurofilament light-Which is the more suitable biomarker for Huntington's disease? | journal = PLOS ONE | volume = 12 | issue = 2 | pages = e0172762 | date = 27 February 2017 | pmid = 28241046 | pmc = 5328385 | doi = 10.1371/journal.pone.0172762 | bibcode = 2017PLoSO..1272762N | doi-access = free }},</ref> It has also been evaluated as a prognostic marker for functional outcome following acute ischemic stroke.<ref>{{Cite journal|last1=Liu|first1=Daoshen|last2=Chen|first2=Jing|last3=Wang|first3=Xuanying|last4=Xin|first4=Jialun|last5=Cao|first5=Ruili|last6=Liu|first6=Zhirong|date=June 2020|title=Serum Neurofilament Light Chain as a Predictive Biomarker for Ischemic Stroke Outcome: A Systematic Review and Meta-analysis|url=https://linkinghub.elsevier.com/retrieve/pii/S105230572030197X|journal=Journal of Stroke and Cerebrovascular Diseases|language=en|volume=29|issue=6|pages=104813|doi=10.1016/j.jstrokecerebrovasdis.2020.104813|pmid=32305278|s2cid=216029229 |url-access=subscription}}</ref> [[mutation|Mutant]] mice with neurofilament abnormalities have [[phenotypes]] resembling [[amyotrophic lateral sclerosis]].<ref name="pmid14640321">{{cite journal | vauthors = Lalonde R, Strazielle C | title = Neurobehavioral characteristics of mice with modified intermediate filament genes | journal = Reviews in the Neurosciences | volume = 14 | issue = 4 | pages = 369–85 | year = 2003 | pmid = 14640321 | doi = 10.1515/REVNEURO.2003.14.4.369 | s2cid = 23675224 }}</ref> 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. . <ref name=”shaw2023”>{{cite journal | last=Shaw | first=Gerry | last2=Madorsky | first2=Irina | last3=Li | first3=Ying | last4=Wang | first4=YongSheng | last5=Jorgensen | first5=Marda | last6=Rana | first6=Sabhya | last7=Fuller | first7=David D | title=Uman-type neurofilament light antibodies are effective reagents for the imaging of neurodegeneration | journal=Brain Communications | volume=5 | issue=2 | date=2023-03-02 | issn=2632-1297 | pmid=37091583 | pmc=10120172 | doi=10.1093/braincomms/fcad067}}</ref>



== See also ==
* [[Bielschowsky stain]]

== References ==
{{Reflist}}

{{Nervous tissue}}
{{Cytoskeletal Proteins}}

[[Category:Cytoskeleton]]