Abstract
Emerging evidence suggests that apoptosis regulators and executioners may control cell fate, without involving cell death per se. Indeed, several conserved elements of apoptosis are integral components of terminal differentiation, which must be restrictively activated to assure differentiation efficiency, and carefully regulated to avoid cell loss. A better understanding of the molecular mechanisms underlying key checkpoints responsible for neural differentiation, as an alternative to cell death will surely make stem cells more suitable for neuro-replacement therapies. In this review, we summarize recent studies on the mechanisms underlying the non-apoptotic function of p53, caspases, and Bcl-2 family members during neural differentiation. In addition, we discuss how apoptosis-regulatory proteins control the decision between differentiation, self-renewal, and cell death in neural stem cells, and how activity is restrained to prevent cell loss.
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Abbreviations
- AMPA:
-
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
- Bcl-2:
-
B cell lymphoma-2
- CAD:
-
Caspase-activated DNase
- CNS:
-
Central nervous system
- ESC:
-
Embryonic stem cells
- IAP:
-
Inhibitor of apoptosis protein
- iPSC:
-
Induced pluripotent stem cells
- LTP:
-
Long-term potentiation
- MMP:
-
Mitochondrial membrane permeabilization
- MSC:
-
Mesenchymal stem cells
- NGF:
-
Nerve growth factor
- NMDA:
-
N-methyl-D-aspartate
- NSC:
-
Neural stem cells
- PTM:
-
Postranslational modifications
- SVZ:
-
Subventricular zone
- TA:
-
Transactivation domain
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Acknowledgments
The authors thank all the members of the laboratory for critical reading of the manuscript. This study is supported by grant PTDC/SAU-NMC/117877/2010 from Fundação para a Ciência e a Tecnologia, Lisbon, Portugal.
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Solá, S., Aranha, M.M. & Rodrigues, C.M.P. Driving Apoptosis-relevant Proteins Toward Neural Differentiation. Mol Neurobiol 46, 316–331 (2012). https://doi.org/10.1007/s12035-012-8289-2
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DOI: https://doi.org/10.1007/s12035-012-8289-2