Fibroblast growth factor 17 (FGF17), a member of the FGF8 subfamily, plays an important role in the regulation of embryonic development and, as a signaling molecule, plays an important role in the induction and patterning of the embryonic brain.

(Data source: AlphaFold)

FGF17 is composed of 216 amino acids and is a secreted extracellular protein. The main functional domain is the 23-216 segment, which includes an N-type glycosylation modification and a disordered structure at the C-terminus.

(Data source: Uniprot)

Unlike the other two members of the subfamily, FGF17 knockout mice exhibit impaired hindbrain development but are viable. In contrast, knockout of the FGF8 and FGF18 genes leads to embryonic or perinatal lethality and loss of all embryonic mesoderm- and endoderm-derived structures, suggesting that FGF17 may play a lesser role than either FGF8 or FGF18. For a long time, research on FGF17 has been relatively rare. However, a recent report in Nature, highlighting the identification of FGF17 as a key target for restoring oligodendrocyte function in the aging brain, has brought FGF17 back into the spotlight.

The results of the conditioned fear experiment found that the cerebrospinal fluid ( CSF ) of young mice improved the memory function of old mice. Hippocampal transcriptome analysis showed that oligodendrocytes were most sensitive to the CSF environment of young mice, and young CSF could promote the proliferation and differentiation of the hippocampus ( OPC ) of old mice.

To further clarify the mechanism, the researchers explored the signal transduction pathways activated by CSF in young mice. Through RNA metabolic sequencing, they found that serum response factor (SRF) can mediate the pro-proliferative effect of CSF in young mice on oligodendrocyte precursor cells.

The researchers screened CSF for potential SRF activators and identified FGF17 as a candidate molecule that induces SRF signaling. FGF17 expression levels are reduced in aged mice. Infusion of FGF17 induced oligodendrocyte progenitor cell proliferation and improved memory in aged mice, while blocking FGF17 impaired cognitive abilities in young mice.

The study found that CSF from young mice could improve the memory function of old mice, which was related to increased OPC proliferation and hippocampal myelination. FGF17 is critical for improving the cognitive ability of old mice and promoting the proliferation of OPCs in vivo and in vitro, but the level of FGF17 in mouse neurons and human cerebrospinal fluid decreases with age.

This interesting work has made a great contribution to the field of myelin regeneration and provided FGF17 as a potential therapeutic target for improving dementia and neurodegenerative diseases, giving FGF17 new vitality.