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Interplay of autophagy and insulin signaling in neural stem cells
Programmed cell death plays a fundamental role in human health and disease. Apoptosis-based approaches for neurodegenerative diseases often fail to yield neuroprotection, due to non-apoptotic forms of cell death and plasticity in switching between distinct cell death pathways. A fundamental gap in our understanding of molecular mechanisms of non-apoptotic cell death hinders development of novel strategies for treatment of neurodegenerative diseases.
“Autophagic cell death” is associated with the formation of autophagic vacuoles without hallmarks of apoptosis. We have recently reported that hippocampal neural stem (HCN) cells derived from adult rat undergo a non-apoptotic, autophagic cell death following insulin withdrawal. Our study demonstrates that autophagy is the primary cell death mechanism in insulin-deficient HCN cells despite their intact apoptotic capability.
Based on morphological criteria, it is evident that autophagy occurs during neurodegeneration. However, questions about the actual role of autophagy and its molecular mechanisms in neurodegeneration remain to be elucidated.
Over recent years there has been a hot polemical debate about the definition of autophagic cell death, even including the very existence of autophagic cell death in the field of programmed cell death. Insulin-deprived HCN cells provide the bona fide case of autophagic cell death that fulfills the criteria of autophagic cell death at its strict sense. Our study will bring to light the role of autophagy in loss of endogenous neural stem cells in neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.