Fibroblast Growth Factor Modulation in Parkinson's Disease

Fibroblast growth factors (FGFs) comprise a family of signalling proteins that regulate development, metabolism and tissue repair. In Parkinson's disease, the progressive loss of dopaminergic neurons in the substantia nigra gives rise to motor and non-motor symptoms. Modulation of FGFs and their receptors (FGFRs) has emerged as a strategy to promote neuronal survival, attenuate neuroinflammation and restore metabolic homeostasis. Both paracrine factors such as FGF20 and endocrine members such as FGF21 have demonstrated neuroprotective effects in preclinical models, engaging pathways that include mitogen-activated protein kinase, sirtuin-mediated anti-inflammatory signalling and the microbiota–gut–brain axis. Advances in drug repositioning and targeted delivery across the blood–brain barrier (BBB) further underscore the translational potential of FGF modulation for disease-modifying therapies.

Research from Nature Portfolio

Recent studies have used a targeted drug-repositioning approach to identify FDA-approved compounds that upregulate endogenous FGF20 production in the brain. Following in silico screening, several candidates were shown to increase FGF20 synthesis in cellular assays. Oral dosing in rodent models elevated FGF20 levels within the nigrostriatal pathway and conferred modest but significant protection of dopaminergic neurons against neurotoxin-induced lesioning, reducing motor asymmetry. This work highlights the feasibility of boosting an intrinsic neurotrophic factor as a less invasive route to slow nigral degeneration.

Fibroblast Growth Factor Modulation in Parkinson's Disease publication trend

The graph below shows the total number of articles in fibroblast growth factor modulation in parkinson's disease across all publications each year (not limited to Nature Index journals).

Technical terms

Fibroblast growth factor (FGF): A family of 22 proteins involved in cell proliferation, differentiation and survival.

FGF receptor (FGFR): A tyrosine kinase receptor that binds FGFs to initiate intracellular signalling cascades.

Dopaminergic neurons: Neurons that produce dopamine, particularly those in the substantia nigra, whose degeneration underlies Parkinson's disease.

Microglial polarization: The functional shift of microglia between pro-inflammatory (M1) and anti-inflammatory (M2) states.

Blood–brain barrier (BBB): A selective endothelial interface that regulates molecular transport between the bloodstream and the central nervous system.

Microbiota–gut–brain axis: A bidirectional communication network linking the gastrointestinal microbiota, metabolic signals and central nervous system function.

References

1. Fibroblast growth factor 21 ameliorates behavior deficits in Parkinson's disease mouse model via modulating gut microbiota and metabolic homeostasis. CNS Neuroscience & Therapeutics (2023).
2. Efficient treatment of Parkinson’s disease using ultrasonography-guided rhFGF20 proteoliposomes. Drug Delivery (2018).
3. Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease. Frontiers in Aging Neuroscience (2021).
4. Targeted repositioning identifies drugs that increase fibroblast growth factor 20 production and protect against 6-hydroxydopamine-induced nigral cell loss in rats. Scientific Reports (2019).
5. Fibroblast growth factor 20 is protective towards dopaminergic neurons in vivo in a paracrine manner. Neuropharmacology (2018).
6. FGF, Mechanism of Action, Role in Parkinson’s Disease, and Therapeutics. Frontiers in Pharmacology (2021).