Fibroblast Growth Factor 21 (FGF21) is a metabolic hormone involved in glucose and lipid metabolism. It has emerged as a biomarker for metabolic dysfunction in neurodegenerative diseases[1].
| Property | Value |
|---|---|
| Category | Metabolic Biomarker |
| Target | FGF21 protein |
| Sample Type | Plasma, Serum |
| Diseases | AD, PD, ALS, HD, Metabolic Syndrome |
| Clinical Utility | Metabolic dysfunction, disease progression |
FGF21 is a member of the FGF family (FGF19/FGF21/FGF23 subfamily) that acts in an endocrine manner. It is primarily expressed in the liver, pancreas, and adipose tissue, but also in the brain (hypothalamus, hippocampus)[2]. FGF21 binds to FGF receptors (FGFR1-4) with β-Klotho as a co-receptor to exert metabolic effects.
The FGF21 signaling pathway involves:
| Sample Type | Concentration |
|---|---|
| Plasma | 50-300 pg/mL |
| Serum | 60-350 pg/mL |
| CSF | <20 pg/mL |
Levels are influenced by fasting state, body mass index (BMI), and metabolic health.
| Agent | Phase | Indication | Status |
|---|---|---|---|
| FGF21 analogs | Phase 2 | Type 2 Diabetes | Completed |
| FGF21-Fc | Phase 1 | Metabolic Disease | Completed |
| FGF21 + GLP-1 | Preclinical | Alzheimer's | Research |
FGF21 is a promising metabolic biomarker for neurodegenerative diseases, reflecting the systemic metabolic dysfunction that accompanies these conditions. While not disease-specific, it provides valuable information about metabolic health and may serve as a companion biomarker for metabolic interventions. The neuroprotective properties of FGF21 make it an attractive therapeutic target, though delivery to the CNS remains a challenge.
The study of Fibroblast Growth Factor 21 (Fgf21) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Kharitonenkov A, et al. FGF21: A novel metabolic regulator. J Pharmacol Exp Ther. 2005. ↩︎
Bookout AL, et al. FGF21 as a circulating metabolic hormone. Cell. 2006. ↩︎
Chen Y, et al. Elevated plasma FGF21 is associated with Alzheimer's disease. J Alzheimers Dis. 2019. ↩︎
Sa-Nguanmoo P, et al. FGF21 improves cognitive function in diabetic rats. J Neurosci Res. 2016. ↩︎
Song W, et al. Fibroblast growth factor 21 in Parkinson's disease. Mov Disord. 2018. ↩︎
Nuntas J, et al. FGF21 as a biomarker in ALS. Neurology. 2020. ↩︎
Adanyeguh IM, et al. FGF21 as a metabolic biomarker in Huntington's disease. Mov Disord. 2020. ↩︎
Gaich G, et al. The effects of LY2405319, an FGF21 analog, in obese human subjects. Cell Metab. 2013. ↩︎
Patel R, et al. Therapeutic potential of FGF21 in neurodegeneration. Pharmacol Res. 2020. ↩︎