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Paper
Integr. Biol., 2009, 1, 394 - 403, DOI: 10.1039/b902617g
Targeting novel integrative nuclear FGFR1 signaling by nanoparticle-mediated gene transfer stimulates neurogenesis in the adult brain
Ewa K. Stachowiak, Indrajit Roy, Yu-Wei Lee, Mariolina Capacchietti, John M. Aletta, Paras N. Prasad and Michal K. Stachowiak
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.
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