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Fibroblast Growth Factor-2 Signaling in Neurogenesis and Neurodegeneration

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Abstract

Fibroblast growth factor-2 (FGF2), also known as basic FGF, is a multi-functional growth factor. One of the 22-member FGF family, it signals through receptor tyrosine kinases encoding FGFR1-4. FGF2 activates FGFRs in cooperation with heparin or heparin sulfate proteoglycan to induce its pleiotropic effects in different tissues and organs, which include potent angiogenic effects and important roles in the differentiation and function of the central nervous system (CNS). FGF2 is crucial to development of the CNS, which explains its importance in adult neurogenesis. During development, high levels of FGF2 are detected from neurulation onwards. Moreover, developmental expression of FGF2 and its receptors is temporally and spatially regulated, concurring with development of specific brain regions including the hippocampus and substantia nigra pars compacta. In adult neurogenesis, FGF2 has been implicated based on its expression and regulation of neural stem and progenitor cells in the neurogenic niches, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. FGFR1 signaling also modulates inflammatory signaling through the surface glycoprotein CD200, which regulates microglial activation. Because of its importance in adult neurogenesis and neuroinflammation, manipulation of FGF2/FGFR1 signaling has been a focus of therapeutic development for neurodegenerative disorders, such as Alzheimer’s disease, multiple sclerosis, Parkinson’s disease and traumatic brain injury. Novel strategies include intranasal administration of FGF2, administration of an NCAM-derived FGFR1 agonist, and chitosan-based nanoparticles for the delivery of FGF2 in pre-clinical animal models. In this review, we highlight current research towards therapeutic interventions targeting FGF2/FGFR1 in neurodegenerative disorders.

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Acknowledgments

We would like to thank Dr. Tomomi Kiyota for the Affymetrix GeneChip analysis of the AAV-FGF2 and AAV-GFP-injected AD mouse model study. This work is supported in part by NIH Training Grant 5 T32 GM008541 (MEW) in association with the Biomolecular Pharmacology Training Program

Conflict of Interest Disclosure

The author have neither a financial nor a personal relationship that might bias this work.

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  1. Graduate Program in Neuroscience, Boston University School of Medicine, Boston, MA, 02118, USA

    Maya E. Woodbury

  2. Departments of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, 72 E. Concord St. L-606, Boston, MA, 02118, USA

    Maya E. Woodbury & Tsuneya Ikezu

  3. Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA

    Tsuneya Ikezu

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Woodbury, M.E., Ikezu, T. Fibroblast Growth Factor-2 Signaling in Neurogenesis and Neurodegeneration. J Neuroimmune Pharmacol 9, 92–101 (2014). https://doi.org/10.1007/s11481-013-9501-5

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