Autophagy for the quality control of adult hippocampal neural stem cells

• Programmed cell death is important in regulating the pool of neural stem cells.
• Insulin withdrawal induces cell death in adult hippocampal neural stem (HCN) cells.
• Autophagic cell death (ACD) is the primary cell death mode by insulin withdrawal.
• GSK-3β and calpain are the key regulators of ACD in HCN cells.

Autophagy plays an important role in neurodegeneration, as well as in normal brain development and function. Recent studies have also implicated autophagy in the regulation of stemness and neurogenesis in neural stem cells (NSCs). However, little is known regarding the roles of autophagy in NSC biology. It has been shown that in addition to cytoprotective roles of autophagy, pro-death autophagy, or ׳autophagic cell death (ACD),’ regulates the quantity of adult NSCs. A tight regulation of survival and death of NSCs residing in the neurogenic niches through programmed cell death (PCD) is critical for maintenance of adult neurogenesis. ACD plays a primary role in the death of adult hippocampal neural stem (HCN) cells following insulin withdrawal. Despite the normal apoptotic capability of HCN cells, they are committed to death by autophagy following insulin withdrawal, suggesting the existence of a unique regulatory program that controls the mode of cell death. We propose that dual roles of autophagy for maintenance of NSC pluripotency, as well as for elimination of defective NSCs, may serve as a combined NSC quality control mechanism.This article is part of a Special Issue entitled SI:Autophagy.