title: Death receptors and mitochondria: two prime triggers of neural apoptosis and differentiation.
abstract: BACKGROUND
  Stem 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.
  
  
  METHODS
  This 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.
  
  
  CONCLUSIONS
  Emerging 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.
  
  
  CONCLUSIONS
  A 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.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences, Lisbon, Portugal. susana.sola@ff.ul.pt
authors.forename: Susana
authors.initials: S
authors.lastname: Solá
authors.forename: Ana L
authors.initials: AL
authors.lastname: Morgado
authors.forename: Cecília M P
authors.initials: CM
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D058953:Neural Stem Cells / Q000378:metabolism* / Q000637:transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism*; D033581:Stem Cell Transplantation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053218:Receptors, Death Domain; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D020169:Caspases