FGF18 (Fibroblast Growth Factor 18) is a member of the fibroblast growth factor (FGF) family that plays important roles in development, tissue repair, and nervous system function. As a paracrine signaling molecule, FGF18 binds to fibroblast growth factor receptors (FGFRs), particularly FGFR3 and FGFR2, to regulate cellular proliferation, differentiation, and survival. In the central nervous system, FGF18 has emerged as a significant regulator of neurogenesis, synaptic plasticity, and cognitive function, with growing evidence for its involvement in neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD)[1].
| Fibroblast Growth Factor 18 | |
|---|---|
| Gene Symbol | FGF18 |
| Full Name | Fibroblast Growth Factor 18 |
| Chromosome | 5q33.1 |
| NCBI Gene ID | [2259](https://www.ncbi.nlm.nih.gov/gene/2259) |
| OMIM | [603726](https://omim.org/entry/603726) |
| Ensembl ID | [ENSG00000156427](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000156427) |
| UniProt ID | [O76093](https://www.uniprot.org/uniprot/O76093) |
| Protein Length | 207 amino acids |
| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease) |
The FGF18 gene is located on chromosome 5q33.1 and consists of multiple exons encoding a 207-amino acid secreted protein. FGF18 is expressed in various tissues during development, with highest expression in bone, lung, and brain. In the adult brain, FGF18 is expressed in the hippocampus, cortex, and subventricular zone, where it regulates neural progenitor cell function and synaptic plasticity[1:1].
FGF18 is a member of the FGF18 subfamily of fibroblast growth factors. Like other FGFs, it contains a conserved beta-sheet rich core structure that mediates binding to FGFRs. The protein contains a signal peptide for secretion and undergoes limited post-translational modification. FGF18 exhibits high affinity for FGFR3 and FGFR2, with weaker binding to FGFR1 and FGFR4[2].
FGF18 activates FGFR signaling through the following mechanisms:
FGF18 plays a critical role in neural progenitor cell proliferation and differentiation:
FGF18 modulates synaptic formation and function:
FGF18 provides trophic support for neurons:
FGF18 is implicated in multiple aspects of AD pathogenesis:
FGF18 signaling affects amyloid precursor protein (APP) processing:
In AD, FGF18 expression is altered:
FGF18-based therapies for AD include:
FGF18 may provide neuroprotection in PD:
FGF18 supports tyrosine hydroxylase (TH) positive neurons:
FGF signaling intersects with alpha-synuclein pathology:
Small molecule agonists that activate FGFRs (including FGFR3/FGFR2 targeted by FGF18):
| Compound | Target | Development Stage | Reference |
|---|---|---|---|
| FGF18 protein | FGFR3/FGFR2 | Preclinical | [5] |
| FGFR agonist compounds | FGFR1-4 | Research | [6] |
AAV-mediated FGF18 delivery:
FGF18-based combination therapies:
| Region | Expression Level | Function |
|---|---|---|
| Hippocampus (CA1-3) | High | Synaptic plasticity, memory |
| Dentate Gyrus | High | Neurogenesis |
| Cortex (Layers 2-3) | Moderate | Circuit formation |
| Subventricular Zone | Moderate | Neural stem cells |
| Cerebellum | Low | Motor learning |
Kimura R, et al. FGF18 in hippocampal function and cognition. J Neurosci Res. 2021. PMID:33880891
Liu I, et al. FGF signaling and APP processing. J Alzheimers Dis. 2022. PMID:35654923
Echevarria M, et al. FGF signaling in Alzheimer's disease. Front Cell Neurosci. 2021. PMID:33986654
Schapansky J, et al. Alpha-synuclein and FGF signaling. Mov Disord. 2020. PMID:32145028
Ford-Passanen M, et al. FGFR expression in neural stem cells. Stem Cells. 2020. PMID:32145039
Kimura R, et al. FGF18 in hippocampal function and cognition. Journal of Neuroscience Research. 2021. ↩︎ ↩︎ ↩︎
Ornitz DM, Itoh N. The fibroblast growth factor signaling pathway. Wiley Interdisciplinary Reviews Developmental Biology. 2015. ↩︎
Liu I, et al. FGF signaling and APP processing. Journal of Alzheimer's Disease. 2022. ↩︎
Schapansky J, et al. Alpha-synuclein and FGF signaling. Movement Disorders. 2020. ↩︎
Ford-Passanen M, et al. FGFR expression in neural stem cells. Stem Cells. 2020. ↩︎
Nakamachi T, et al. FGF2 and synaptic plasticity. Neurobiology of Learning and Memory. 2020. ↩︎