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Driving Apoptosis-relevant Proteins Toward Neural Differentiation

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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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  1. Márcia M. Aranha

    Present address: Champalimaud Centre for the Unknown, Lisbon, Portugal

Authors and Affiliations

  1. Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

    Susana Solá, Márcia M. Aranha & Cecília M. P. Rodrigues

  2. Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

    Susana Solá & Cecília M. P. Rodrigues

  3. Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal

    Susana Solá

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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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