Death receptors and mitochondria: Two prime triggers of neural apoptosis and differentiation |
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Authors: | Susana Solá ,Ana L. Morgado,Cecí lia M.P. Rodrigues |
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Affiliation: | 1. Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Lisbon, Portugal;2. Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal |
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Abstract: | BackgroundStem cell therapy is a strategy far from being satisfactory and applied in the clinic. Poor survival and differentiation levels of stem cells after transplantation or neural injury have been major problems. Recently, it has been recognized that cell death-relevant proteins, notably those that operate in the core of the executioner apoptosis machinery are functionally involved in differentiation of a wide range of cell types, including neural cells.Scope of reviewThis article will review recent studies on the mechanisms underlying the non-apoptotic function of mitochondrial and death receptor signaling pathways during neural differentiation. In addition, we will discuss how these major apoptosis-regulatory pathways control the decision between differentiation, self-renewal and cell death in neural stem cells and how levels of activity are restrained to prevent cell loss as final outcome.Major conclusionsEmerging evidence suggests that, much like p53, caspases and Bcl-2 family members, the two prime triggers of cell death pathways, death receptors and mitochondria, may influence proliferation and differentiation potential of stem cells, neuronal plasticity, and astrocytic versus neuronal stem cell fate decision.General significanceA better understanding of the molecular mechanisms underlying key checkpoints responsible for neural differentiation as an alternative to cell death will surely contribute to improve neuro-replacement strategies. |
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Keywords: | Apaf-1, apoptosis protease activating factor-1 Bcl-2, B-cell lymphoma-2 CNS, central nervous system ESCs, embryonic stem cells IAPs, inhibitor of apoptosis proteins IL-1α/β, interleukin-1 α/β iPSCs, induced pluripotent stem cells miRNAs, microRNAs MMP, mitochondrial membrane permeabilization MSCs, mesenchymal stem cells mtDNA, mitochondrial DNA NPCs, neural progenitor cells NSCs, neural stem cells NF-κB, nuclear factor-κB ROS, reactive oxygen species SVZ, subventricular zone TNF, tumor necrosis factor TNF-α, TNF ligand α TNFR1/2, TNF-receptor type 1/2 |
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