Fibroblast Growth Factor Signalling in the Diseased Nervous System

Molecular Neurobiology, 2021 · DOI: https://doi.org/10.1007/s12035-021-02367-0 · Published: April 15, 2021

Simple Explanation

Fibroblast growth factors (FGFs) are important signaling molecules in the brain for development, maintenance, and repair, influencing communication between myelinating cells and axons, as well as astrocytes, microglia, neurons, and synapses. Recent advancements in genetics and imaging have provided insights into FGF signaling, revealing the significance of FGF receptors in neurons and glial cells for tissue protection, axon regeneration, glial proliferation, and behavior. This review summarizes recent findings on the role of FGFs and their receptors in the nervous system and in the development of major neurological and psychiatric disorders.

Study Duration

Not specified

Participants

Mainly rats and mice, some human aspects validated

Evidence Level

Not specified

Key Findings

1
FGFs play a crucial role in the regeneration and repair of the nervous system, with FGFR1 and FGFR2 stimulation inducing neural tissue regeneration in planarians and vertebrate embryos.
2
FGF22 regulates the formation of new excitatory synaptic contacts and is expressed in spinal interneurons and long propriospinal neurons.
3
FGF2 and FGF20 synergize to increase dopaminergic neuron numbers, with FGF20 preferentially expressed in the substantia nigra.

Research Summary

Fibroblast growth factors (FGFs) act as key signalling molecules in brain development, maintenance, and repair. Conditional mouse mutants have revealed the functional significance of neuronal and glial FGF receptors, not only in tissue protection, axon regeneration, and glial proliferation but also in instant behavioural changes. This review provides a summary of recent findings regarding the role of FGFs and their receptors in the nervous system and in the pathogenesis of major neurological and psychiatric disorders.

Practical Implications

Therapeutic Potential for Neurological Disorders

Modulating FGF signaling may offer new therapeutic avenues for treating various neurological disorders, including spinal cord injury, Alzheimer's disease, and Parkinson's disease.

Psychiatric Disorder Treatments

Understanding the role of FGFs in psychiatric disorders, such as schizophrenia and depression, could lead to the development of novel treatments targeting FGF signaling pathways.

Enhancing Axon Regeneration

Strategies to stimulate FGF signaling and overcome inhibitory factors could promote axon regeneration and functional recovery after CNS injuries.

Study Limitations

1
Poor blood-brain barrier penetration of FGFs
2
Short half-life of FGFs and vulnerability to proteolytic cleavage
3
Uncertainty whether FGFR-induced alterations are causes or consequences of pathological processes

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