NFASC — Neurofascin
Overview
Nfasc — Neurofascin plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
<div class="infobox infobox-gene"> [@neurofascin2018]
<table> [@nfasc]
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">NFASC — Neurofascin</th></tr> [@axonglia2019]
<tr><td><strong>Gene Symbol</strong></td><td>NFASC</td></tr> [@neurofascin2020]
<tr><td><strong>Full Name</strong></td><td>Neurofascin</td></tr>
<tr><td><strong>Chromosome</strong></td><td>1q32.1</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[4764](https://www.ncbi.nlm.nih.gov/gene/4764)</td></tr>
<tr><td><strong>OMIM</strong></td><td>609014</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000163508</td></tr>
<tr><td><strong>UniProt</strong></td><td>[Q14807](https://www.uniprot.org/uniprot/Q14807)</td></tr>
<tr><td><strong>Protein Name</strong></td><td>Neurofascin</td></tr>
<tr><td><strong>Protein Length</strong></td><td>1245 amino acids (isoform 1)</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~140-180 kDa (depending on isoform)</td></tr>
<tr><td><strong>Brain Expression</strong></td><td>High in brain, particularly in axons and myelin</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Charcot-Marie-Tooth Disease](/diseases/charcot-marie-tooth), [Multiple Sclerosis](/diseases/multiple-sclerosis), [ALS](/diseases/amyotrophic-lateral-sclerosis)</td></tr>
</table>
</div>
Introduction
NFASC (Neurofascin) is a member of the L1 family of cell adhesion molecules (L1-CAMs). Neurofascin is a critical regulator of axon guidance, node of Ranvier formation, and synapse formation in the nervous system. NFASC mutations cause inherited peripheral neuropathies (Charcot-Marie-Tooth disease) and encephalopathies, while altered neurofascin expression is implicated in multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and other neurodegenerative conditions.
Gene Structure and Expression
Genomic Location
The NFASC gene is located on chromosome 1q32.1 and consists of approximately 35 exons spanning about 80 kb of genomic DNA. The gene undergoes alternative splicing to produce multiple isoforms with distinct functions.
NFASC produces multiple isoforms:
- NFASC186 (Neurofascin-186): Axonal isoform, concentrated at the node of Ranvier
- NFASC155: Glial isoform, expressed by oligodendrocytes
- NFASC140: Alternative isoform
- NFASC164: Brain-enriched isoform
Brain Expression Pattern
NFASC is expressed predominantly in the nervous system:
- Axonal membrane (NFASC186)
- Oligodendrocyte processes (NFASC155)
- Growth cones during development
- Synaptic membranes
Expression data from the Allen Human Brain Atlas shows high NFASC expression in:
- Cerebral [cortex](/brain-regions/cortex) (pyramidal neurons)
- Corpus callosum (white matter)
- Cerebellar white matter
- Spinal cord [1](https://human.brain-map.org/)
Protein Structure and Function
L1-CAM Family
Neurofascin belongs to the L1 family of immunoglobulin superfamily cell adhesion molecules (IgSF CAMs), which includes:
Structural Features
The neurofascin protein contains:
Extracellular domain:
- 6 Ig-like domains (Ig1-Ig6)
- 5 Fibronectin type III repeats (FN1-FN5)
- N-terminal signal peptide
Transmembrane domain: Single-pass membrane anchor
Cytoplasmic domain: Ankyrin-binding site, involved in cytoskeletal interactionsBiological Functions
Axon Guidance
During development, neurofascin mediates:
Growth cone guidance: Directs axon growth through extracellular cues
Fasciculation: Promotes axon bundling
Target recognition: Helps [neurons](/entities/neurons) find appropriate targetsNeurofascin is essential for node of Ranvier formation:
Node assembly: NFASC186 clusters at developing nodes
Ankyrin-G interaction: Binds ankyrin-G to stabilize nodal proteins
Ion channel clustering: Recruits voltage-gated sodium channelsThe nodal complex includes:
- Voltage-gated Na⁺ channels (Nav1.2, Nav1.6)
- Ankyrin-G
- βIV-spectrin
- NFASC186
Myelin Organization
In the central nervous system:
- NFASC155 on oligodendrocytes contacts NFASC186 on axons
- Maintains paranodal structure
- Ensures proper saltatory conduction
Neurofascin contributes to:
- Synaptogenesis
- Synaptic plasticity
- Dendritic spine formation
Disease Associations
Charcot-Marie-Tooth Disease (CMT)
NFASC mutations cause a subtype of CMT (CMT2):
- Inheritance: Autosomal recessive
- Phenotype: Peripheral neuropathy with variable CNS involvement
- Onset: Early childhood
- Features: Motor weakness, sensory loss, foot deformities
| Mutation Type | Phenotype |
|--------------|-----------|
| Missense | Mild CMT2 |
| Nonsense/Frameshift | Severe encephalopathy |
| splice-site | Variable |
Multiple Sclerosis (MS)
In MS lesions:
- Altered NFASC expression: Disrupted node of Ranvier
- Demyelination: Loss of paranodal NFASC
- Axonal degeneration: Secondary to demyelination
NFASC is being investigated as a biomarker for:
- Disease progression
- Treatment response
Amyotrophic Lateral SALS
NFASC is implicated in ALS:
Altered expression: Changed NFASC levels in ALS motor neurons
Axonal dysfunction: Impaired node of Ranvier maintenance
Synaptic deficits: Altered neuromuscular junction formation
Molecular Mechanisms in Neurodegeneration
Node of Ranvier Disruption
In neurodegenerative diseases:
NFASC mislocalization: Loss from nodal/paranodal regions
Sodium channel dispersion: Reduced channel clustering
Conduction deficits: Impaired nerve conductionAxonal Degeneration
NFASC deficiency leads to:
- Impaired axon-glia interactions
- Axonal cytoskeletal abnormalities
- Progressive neurodegeneration
Neuroinflammation
In MS and other conditions:
- Inflammatory cytokines downregulate NFASC
- Immune cells target NFASC-expressing cells
Therapeutic Implications
Target for Therapy
NFASC represents a therapeutic target:
Remyelination: Promote NFASC expression for repair
Node stabilization: Maintain sodium channel clustering
Gene therapy: AAV-delivered NFASCBiomarker Potential
NFASC in cerebrospinal fluid may serve as:
- MS disease activity marker
- Axonal injury marker
See Also
- [NFASC Protein](/proteins/nfasc-protein) — Detailed protein information
- [Charcot-Marie-Tooth Disease](/diseases/charcot-marie-tooth-disease) — CMT overview
- [Multiple Sclerosis](/diseases/multiple-sclerosis) — MS overview
- [Node of Ranvier](/mechanisms/node-ranvier) — Node biology
- [Axon Guidance](/mechanisms/axon-guidance) — Development mechanisms
- [Genes](/genes) — All gene pages
- [Proteins](/proteins) — All protein pages
External Links
- [NCBI Gene — NFASC](https://www.ncbi.nlm.nih.gov/gene/4764)
- [UniProt — NFASC](https://www.uniprot.org/uniprot/Q14807)
- [Ensembl — NFASC](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000163508)
- [Allen Human Brain Atlas](https://human.brain-map.org/)
- [OMIM — NFASC](https://www.omim.org/entry/609014)
Overview
Nfasc — Neurofascin plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Nfasc — Neurofascin has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
Unknown, Allen Human Brain Atlas — NFASC Expression (n.d.)
[Unknown, Neurofascin in node of Ranvier formation and function (2018)](https://doi.org/10.1016/j.neuroscience.2018.03.014)
[Unknown, NFASC mutations cause Charcot-Marie-Tooth disease (n.d.)](https://doi.org/10.1093/brain/awx123)
[Unknown, Axon-glia interactions at the node of Ranvier (2019)](https://doi.org/10.1016/j.tics.2019.12.002)
[Unknown, Neurofascin and ALS pathogenesis (2020)](https://doi.org/10.1016/j.neurobiolaging.2020.03.015)