Neural Stem Cell Death Regulation in Nervous System Development and Disease

Abstract

Neural stem cell death is critical for the functional organization of the developing nervous system and altered rates of neural stem cell death lead to a variety of neurodevelopmental pathologies. Neural stem cell death can be categorized as type I (apoptotic), type II (autophagic), or type III (necrotic or cytoplasmic). Studies of mice with targeted gene disruptions in key cell death regulators demonstrate that neural stem cell death pathways are tightly regulated by Bcl-2 family of proteins, caspases, and autophagy-associated proteins. Neural stem cells are also affected by a variety of cytotoxic stimuli that trigger stimulus-specific death pathways. Dysregulated neural stem cell death has been implicated in psychiatric and neurologic disease and the therapeutic potential of neural stem cells in various neurodegenerative conditions makes further investigation of the molecules that regulate neural stem cell death essential. In this chapter, we review the pathways regulating neural stem cell death in response to various pathological stimuli including hypoxia-ischemia, DNA damage, glucorticoid exposure, and lysosomal dysfunction.