NFASC — Neurofascin

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.

...

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.

Isoforms

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:

• L1CAM
• CHL1
• NCAM2

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 interactions

Biological 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 targets

Node of Ranvier Formation

Neurofascin 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 channels

The 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

Synapse Formation

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 conduction

Axonal 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 NFASC

Biomarker 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)