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Issue 5-6, 2009
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Targeting novel integrative nuclear FGFR1 signaling by nanoparticle-mediated gene transfer stimulates neurogenesis in the adult brain

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Abstract

Neurogenesis, the process of differentiation of neuronal stem/progenitor cells (NS/PC) into mature neurons, holds the key to the treatment of various neurodegenerative disorders, which are a major health issue for the world’s aging population. We report that targeting the novel integrative nuclear FGF Receptor 1 signaling (INFS) pathway enhances the latent potential of NS/PCs to undergo neuronal differentiation, thus promoting neurogenesis in the adult brain. Employing organically modified silica (ORMOSIL)–DNA nanoplexes to efficiently transfect recombinant nuclear forms of FGFR1 and its FGF-2 ligand into the brain subventricular zone, we find that INFS stimulates the NS/PC to withdraw from the cell cycle, differentiate into doublecortin expressing migratory neuroblasts and neurons that migrate to the olfactory bulb, subcortical brain regions and in the brain cortex. Thus, nanoparticle-mediated non-viral gene transfer may be used to induce selective differentiation of NS/PCs, providing a potentially significant impact on the treatment of a broad range of neurological disorders.

Graphical abstract: Targeting novel integrative nuclear FGFR1 signaling by nanoparticle-mediated gene transfer stimulates neurogenesis in the adult brain

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Publication details

The article was received on 10 Feb 2009, accepted on 31 Mar 2009 and first published on 08 May 2009


Article type: Paper
DOI: 10.1039/B902617G
Integr. Biol., 2009,1, 394-403

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