Manipulation of Endogenous Neural Stem Cells as a Therapeutic Strategy for Neurodegenerative Diseases: Insights from Animal Models

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The mammalian brain retains the capacity to generate new neurons throughout adulthood through a process referred to as adult neurogenesis. This capacity is restricted to well-defined brain regions, namely the sub-ventricular zone (SVZ) adjacent to the lateral ventricles, and the sub-granular zone (SGZ) of the hippocampal dentate gyrus (DG). Adult neurogenesis and each one of its phases are tightly regulated and can be influenced by multiple behavioral, physiological, and pathological factors. Indeed, mounting evidence from animal models has indicated that neurodegenerative conditions such as Alzheimer’s disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) may be associated with altered neurogenic function. Importantly, alterations in adult hippocampal neurogenesis may be responsible, at least in part, for some of the cognitive deficits observed in animal models of these neurodegenerative conditions as well as individuals afflicted with these disorders. On the other hand, since adult neural progenitors have been proposed as an endogenous source of healthy neurons, it has been suggested that harnessing the endogenous neurogenic capacity in the diseased brain might be of therapeutic value for these neurodegenerative conditions. In this chapter we review the results obtained in rodent models of AD, PD, and HD with regards to therapies aimed at restoring adult neurogenesis and discuss whether such therapies might have therapeutic relevance for the treatment of these devastating neurodegenerative disorders.