Introduction
The predominant disease that mutant FGFR3 (fibroblast growth factor receptor 3) gene causes is Achondroplasia. Furthermore, Achondroplasia means the absence of chondrocyte formation in bones. Additionally, the transformation of chondrocytes into bone cells is prevalent in the limbs as well as the facial bones of humans (1). Therefore, the predominant symptom of Achondroplasia is bone growth retardation and is found in the limbs as well as facial bones. The majority of people diagnosed with Achondroplasia have parents that are genotypically and phenotypically normal for the FGFR3 gene; moreover, this means that the FGFR3 mutation was not inherited from the parents but arose as a de novo mutation. However, once diagnosed with Achondroplasia …show more content…
The functions of FGFR3 are dependent on ligands, specifically fibroblast growth factor (FGF) and heparin sulfate proteoglycans (6). These ligands bind to the D2, and D3 immunoglobulin subdomains of FGFR3 to stabilize the dimer complex as well as augment the functions of FGFR3. Conversely, D1 functions to inhibit FGFR3. Although the D2 and D3 immunoglobulins trigger the functions of FGFR3. FGFR3 can phosphorylate marginally without the ligation of fibroblast growth factors. This phosphorylation of FGFR3 in the absence of a bound ligand is termed “basal” phosphorylation. Once a ligand binds, a dimeric adapter protein Grb2 inhibits the basal phosphorylation of FGFR3 by catching the mobile kinase domain C-termini. Complete active phosphorylation and basal phosphorylation of the mutant FGFR3 gene are the fundamental components of what causes Achondroplasia. The normal function of the FGFR3 gene is to regulate the proliferation and differentiation of chondrocytes in bones; moreover, the negative feedback of chondrocyte production provided by FGFR3 regulates bone growth (7). Once the fibroblast growth factor is bound, an MAPK signal pathway is initiated by FGFR3. Furthermore, the MAPK pathway can now relay the extracellular signal to trigger an intracellular response. The intracellular response provided by MAPK, …show more content…
These therapeutic experiments have led to the use of sFGFR3, statin, meclizine, and NVP-BGJ398, and BMN 111 as possible solutions (16-20). All of the possible cures to Achondroplasia take into account the different functions of FGFR3 and produce an anti function such as blocking receptor activation and inhibiting downstream signals (19). Moreover, the most promising method is the use of BMN 111, a CNP (C-type natriuretic peptide) analog. BMN 111 is a positive regulator of bone growth; moreover, BMN 111 promotes bone growth by inhibiting the MAPK (mitogen-activated protein kinase) pathway that is transmitted by FGFR3. Another feature of BMN 111 that allows it to promote positive regulation of bone growth for an extended period of time is due to its resistance from neutral-endopeptidase (NEP) (18,
The predominant disease that mutant FGFR3 (fibroblast growth factor receptor 3) gene causes is Achondroplasia. Furthermore, Achondroplasia means the absence of chondrocyte formation in bones. Additionally, the transformation of chondrocytes into bone cells is prevalent in the limbs as well as the facial bones of humans (1). Therefore, the predominant symptom of Achondroplasia is bone growth retardation and is found in the limbs as well as facial bones. The majority of people diagnosed with Achondroplasia have parents that are genotypically and phenotypically normal for the FGFR3 gene; moreover, this means that the FGFR3 mutation was not inherited from the parents but arose as a de novo mutation. However, once diagnosed with Achondroplasia …show more content…
The functions of FGFR3 are dependent on ligands, specifically fibroblast growth factor (FGF) and heparin sulfate proteoglycans (6). These ligands bind to the D2, and D3 immunoglobulin subdomains of FGFR3 to stabilize the dimer complex as well as augment the functions of FGFR3. Conversely, D1 functions to inhibit FGFR3. Although the D2 and D3 immunoglobulins trigger the functions of FGFR3. FGFR3 can phosphorylate marginally without the ligation of fibroblast growth factors. This phosphorylation of FGFR3 in the absence of a bound ligand is termed “basal” phosphorylation. Once a ligand binds, a dimeric adapter protein Grb2 inhibits the basal phosphorylation of FGFR3 by catching the mobile kinase domain C-termini. Complete active phosphorylation and basal phosphorylation of the mutant FGFR3 gene are the fundamental components of what causes Achondroplasia. The normal function of the FGFR3 gene is to regulate the proliferation and differentiation of chondrocytes in bones; moreover, the negative feedback of chondrocyte production provided by FGFR3 regulates bone growth (7). Once the fibroblast growth factor is bound, an MAPK signal pathway is initiated by FGFR3. Furthermore, the MAPK pathway can now relay the extracellular signal to trigger an intracellular response. The intracellular response provided by MAPK, …show more content…
These therapeutic experiments have led to the use of sFGFR3, statin, meclizine, and NVP-BGJ398, and BMN 111 as possible solutions (16-20). All of the possible cures to Achondroplasia take into account the different functions of FGFR3 and produce an anti function such as blocking receptor activation and inhibiting downstream signals (19). Moreover, the most promising method is the use of BMN 111, a CNP (C-type natriuretic peptide) analog. BMN 111 is a positive regulator of bone growth; moreover, BMN 111 promotes bone growth by inhibiting the MAPK (mitogen-activated protein kinase) pathway that is transmitted by FGFR3. Another feature of BMN 111 that allows it to promote positive regulation of bone growth for an extended period of time is due to its resistance from neutral-endopeptidase (NEP) (18,