CFL1 Gene

CFL1 Gene

Introduction

Cfl1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@supsup2022]
<table> [@supsup2023]
<tr><th>Gene Symbol</th><td>CFL1</td></tr> [@supsup2021]
<tr><th>Full Name</th><td>Cofilin 1</td></tr> [@supsup2022a]
<tr><th>Chromosomal Location</th><td>14q24.1</td></tr>
<tr><th>NCBI Gene ID</th><td>1072</td></tr>
<tr><th>OMIM</th><td>601243</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000132716</td></tr>
<tr><th>UniProt ID</th><td>P23528</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Stroke</td></tr>
</table>
</div>

Overview

CFL1 Gene

Introduction

Cfl1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@supsup2022]
<table> [@supsup2023]
<tr><th>Gene Symbol</th><td>CFL1</td></tr> [@supsup2021]
<tr><th>Full Name</th><td>Cofilin 1</td></tr> [@supsup2022a]
<tr><th>Chromosomal Location</th><td>14q24.1</td></tr>
<tr><th>NCBI Gene ID</th><td>1072</td></tr>
<tr><th>OMIM</th><td>601243</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000132716</td></tr>
<tr><th>UniProt ID</th><td>P23528</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Stroke</td></tr>
</table>
</div>

Overview

CFL1 (Cofilin 1) encodes a member of the actin-depolymerizing factor/cofilin family, which plays a critical role in regulating actin cytoskeleton dynamics. This protein is essential for neuronal development, synaptic plasticity, and axonal transport. Dysregulation of CFL1 has been implicated in multiple neurodegenerative diseases.

Function

Cofilin 1 is a small actin-binding protein (19 kDa) that promotes the disassembly and reassembly of actin filaments. It plays key roles in:

• Actin Filament Turnover: Cofilin binds to aged or ADP-actin subunits within filaments, promoting their depolymerization and enabling rapid actin dynamics essential for cellular motility, endocytosis, and cytokinesis.
• Neuronal Morphogenesis: In [neurons](/entities/neurons), cofilin regulates actin dynamics in growth cones, [dendritic spines](/cell-types/dendritic-spines), and axonal branches, influencing neuronal migration, axon guidance, and synapse formation.
• Synaptic Plasticity: Activity-dependent actin remodeling at synaptic sites is critical for [long-term potentiation](/mechanisms/long-term-potentiation) (LTP) and long-term depression (LTD). Cofilin-mediated actin cycling regulates spine morphology and synaptic strength.
• Axonal Transport: The actin cytoskeleton provides tracks for myosin-based transport in regions where microtubules are sparse. Cofilin regulates this process in axons and dendrites.
• Nuclear Functions: Cofilin can translocate to the nucleus where it may regulate gene expression and chromatin remodeling.

Disease Associations

Alzheimer's Disease

• [Aβ](/proteins/amyloid-beta) oligomers induce cofilin activation and actin cytoskeleton disruption in neurons
• Cofilin rod formation (actin-cofilin rods) is observed in AD brain tissue
• Dysregulated cofilin signaling contributes to synaptic loss and dendritic spine degeneration
• Cofilin activation links to mitochondrial dysfunction and oxidative stress in AD

Parkinson's Disease

• [α-Synuclein](/proteins/alpha-synuclein) aggregates sequester cofilin, disrupting actin dynamics
• Cofilin dysregulation contributes to dopaminergic neuron vulnerability
• Impaired actin-based transport affects mitochondrial function and [autophagy](/entities/autophagy)
• [LRRK2](/entities/lrrk2) mutations may affect cofilin phosphorylation status

Amyotrophic Lateral Sclerosis

• [TDP-43](/proteins/tdp-43) proteinopathy disrupts cofilin signaling pathways
• Mutant SOD1 affects actin cytoskeleton in motor neurons
• Cofilin rod formation observed in ALS models and patient tissue
• Impaired axonal transport contributes to motor neuron degeneration

Stroke and Brain Injury

• Ischemic stroke rapidly activates cofilin signaling
• Cofilin-mediated actin disassembly contributes to excitotoxic cell death
• Cofilin rods form in response to oxygen-glucose deprivation
• Targeting cofilin may provide neuroprotective strategies

Expression Pattern

Cofilin 1 is ubiquitously expressed with highest levels in:

• Brain (cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum)
• Muscle tissue
• Hematopoietic cells

• Pyramidal neurons (cortical layer 2/3, CA1-CA3)
• Dentate gyrus granule cells
• Cerebellar Purkinje cells
• [Astrocytes](/entities/astrocytes) and [microglia](/entities/microglia)

Therapeutic Implications

• Actin-Stabilizing Drugs: Jasplakinolide and latrunculin derivatives are being explored to stabilize actin filaments
• Cofilin Modulators: Small molecules targeting cofilin phosphorylation (LIMK1/2 inhibitors)
• LIMK Inhibitors: BMS-5 and similar compounds prevent cofilin inactivation
• Gene Therapy: Viral vectors expressing wild-type cofilin to restore function

Research Directions

• Understanding cofilin rod formation in neurodegeneration
• Developing brain-penetrant LIMK inhibitors
• Cofilin as a biomarker for synaptic dysfunction
• Interaction between cofilin and [tau](/proteins/tau) pathology

Animal Models

• CFL1 knockout mice show embryonic lethality
• Conditional knockout mice reveal roles in neuronal development
• Transgenic mice expressing mutant cofilin show AD-like phenotypes
• Drosophila models (twinstar) demonstrate conserved functions

Background

The study of Cfl1 Gene 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.

External Links

• [NCBI Gene: CFL1](https://www.ncbi.nlm.nih.gov/gene/1072)
• [UniProt: P23528](https://www.uniprot.org/uniprot/P23528)
• [Ensembl: ENSG00000132716](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000132716)
• [GeneCards: CFL1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CFL1)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving CFL1 Gene discovered through SciDEX knowledge graph analysis: