Fibroblast Growth Factor 20 (FGF20) protein is an integral part of the fibroblast growth factor (FGF) family, best known for its diverse range of functions, including regulation of cellular proliferation, differentiation, and migration. It plays a significant role in developmental processes and tissue repair mechanisms.
Background of FGF20 Protein
The FGF20 gene was initially identified in 2000 by studying genomic sequences from mouse and human. The gene encoding for this protein is located on chromosome 8p22 in humans and chromosome 15 E2 in mice, specifically situated between the markers D8S277 and D8S273. The FGF20 gene, approximately 6722 base pairs in length, encompasses five exons separated by four introns.
For the FGF20 protein structure, it is composed of 211 amino acids with a molecular weight of roughly 23 kilodaltons. The protein structure has been categorized into a three-dimensional architecture consisting of 12 antiparallel beta strands, forming a beta-trefoil configuration. Like other FGFs, it contains a heparin-binding domain, helping it interact with heparan sulfate proteoglycans to elicit the cell-signaling process.
FGF20 Protein Function and Related Signaling Pathways
The primary function of the FGF20 protein relates to its involvement in neurogenesis, stimulating neuronal differentiation, and proliferation. Particularly, it's found to have a significant influence on the dopaminergic neurons within the substantia nigra of the brain.
FGF20 protein utilizes its signals through four types of FGF receptors (FGFRs). The signaling pathway associated with FGF20 protein primarily revolves around the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway. When FGF20 binds with FGFR, it dimerizes the receptors and stimulates the downstream MAPK-ERK pathway. Another vital pathway is the PI3K-Akt pathway, responsible for several critical cellular processes, including cell cycle progression and survival. Through these pathways, FGF20 manages and mediates cellular division, differentiation, and movement.
FGF20 Protein-Related Diseases and Role in Diseases
The FGF20 protein has been linked to several diseases, primarily neurological disorders. Overexpression of FGF20 has been implicated in Parkinson's disease (PD). The higher amounts of FGF20 may lead to an excess alpha-synuclein, a protein that builds up to toxic levels in the brain cells of people with PD. Furthermore, research indicates downregulation of FGF20 could be associated with Alzheimer's disease due to its potential protective role against β-amyloid toxicity. Additionally, it's linked with tumor progression and angiogenesis in certain types of cancer, like breast and prostate cancer.
Application of FGF20 Protein in Medicine
Given its significant role in various diseases, FGF20 protein possesses potential therapeutic value. For Parkinson's disease, controlling the expression of FGF20 may provide relief by decreasing the toxic aggregation of alpha-synuclein. Similarly, enhancing FGF20 expression in Alzheimer's could potentially improve neuronal survival. In the context of cancer, targeting FGF20 signaling pathway could potentially help in inhibiting tumor growth and progression.
Drug Candidates Related to FGF20 Protein
Currently, research is centered on profiling drug candidates that target FGF20 functions or its related signaling pathway. Some of these candidates include Ponatinib and Dovitinib that are multi-targeted kinase inhibitors and have the potential to block FGF signaling in cancer treatment.
