| Gene |
[FN1](/genes/fn1) |
| UniProt |
P02751 |
| PDB |
1E8B, 2M6P |
| Mol. Weight |
272 kDa (monomer), 440 kDa (dimer) |
| Localization |
Extracellular matrix, cell surface, plasma |
| Family |
Fibronectin family (ECM glycoprotein) |
| Diseases |
[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), Brain Injury |
Fibronectin (FN1) is a high-molecular-weight extracellular matrix glycoprotein that plays crucial roles in cell adhesion, migration, and tissue morphogenesis. In the brain, fibronectin is expressed during development and reappears in various pathological conditions including Alzheimer's disease, where it accumulates in Aβ plaques and participates in glial scarring.
FN1 is a large modular glycoprotein:
- N-terminal domain: Involved in fibrin and collagen binding
- Type I repeats: Bind to gelatin/collagen
- Type II repeats: Bind to collagen
- Type III repeats: Cell-binding (RGD sequence), heparin binding
- C-terminal dimerization domain: Forms covalent dimers
The RGD sequence in the 10th type III repeat mediates integrin binding.
In the nervous system:
- Development: Transient expression during brain development
- Cell adhesion: Binds to integrins and other ECM components
- Wound healing: Promotes glial scar formation after injury
- Cell migration: Guides neuronal and glial migration
- Accumulates in and around Aβ plaques
- Fibronectin deposition precedes plaque formation in some models
- Binds to Aβ, potentially promoting aggregation
- Mediates inflammatory responses to Aβ
- Role in astrocyte reactivity around plaques
- Fibronectin expression increased in substantia nigra of PD brains
- Associated with glial scarring
- Mediates microglial activation
- Rapidly upregulated after injury
- Contributes to glial scar formation
- Implicated in post-injury neurodegeneration
Targeting fibronectin:
- FN1-blocking agents to reduce plaque pathology
- Peptide mimics of functional domains
- Gene therapy to modulate FN1 expression
- Fibronectin in Aβ plaque formation (Van Dorpe et al., 1999)
- FN1 in neuroinflammation (Schulze et al., 2021)
- Fibronectin and glial scar (Silver et al., 2019)