Disease targets and strategies for the therapeutic modulation of endogenous neural stem and progenitor cells

Neural stem cells, able to self-renew and give rise to both neurons and glia, line the cerebral ventricles of the adult human brain. Humans also harbor lineage-restricted neuronal progenitors in the hippocampus and glial progenitor cells in both the gray and white matter of the forebrain. These various stem and progenitor cell types may provide targets for pharmacotherapy for a variety of disorders of the central nervous system. Each resident progenitor phenotype may be mobilized and induced to differentiate in vivo by the actions of both exogenous growth factors and small molecule modulators of progenitor-selective signaling pathways. This strategy may be particularly efficacious in neurodegenerations such as Huntington's disease, in which lost neurons may be replenished through the directed induction of progenitor cells lining the ventricular wall of the affected striatum. Similarly, the mobilization of glial progenitor cells may permit the introduction of new oligodendrocytes to demyelinated regions of adult white matter. Our rapidly increasing understanding of the molecular control of progenitor cell mobilization and differentiation should provide a wealth of new opportunities for recruiting endogenous progenitors as a means of treating neurological disease.