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How Does p73 Cause Neuronal Defects?

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Abstract

The p53-family member, p73, plays a key role in the development of the central nervous system (CNS), in senescence, and in tumor formation. The role of p73 in neuronal differentiation is complex and involves several downstream pathways. Indeed, in the last few years, we have learnt that TAp73 directly or indirectly regulates several genes involved in neural biology. In particular, TAp73 is involved in the maintenance of neural stem/progenitor cell self-renewal and differentiation throughout the regulation of SOX-2, Hey-2, TRIM32 and Notch. In addition, TAp73 is also implicated in the regulation of the differentiation and function of postmitotic neurons by regulating the expression of p75NTR and GLS2 (glutamine metabolism). Further still, the regulation of miR-34a by TAp73 indicates that microRNAs can also participate in this multifunctional role of p73 in adult brain physiology. However, contradictory results still exist in the relationship between p73 and brain disorders, and this remains an important area for further investigation.

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Abbreviations

CNS:

Central nervous system

NSC:

Neural stem cell

(MBP):

Myelin basic protein

NGF:

Nerve growth factor

PNS:

Peripheral nervous system

p75NTR :

p75 neurotrophin receptor

WT:

Wild type

TAp73−/−:

TAp73 knockout

p73−/−:

p73 knockout mice

DG:

Dentate gyrus

AD:

Alzheimer’s disease

Aβ:

β-amyloid

NFTs:

Neurofibrillary tangles

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Acknowledgments

We thank Prof Eleonora Candi and Dr Ivano Amelio for scientific discussion. This work has been supported by the Medical Research Council, UK.

Conflict of Interest

The authors declare that they have no competing interests.

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Author notes

  1. Maria Victoria Niklison-Chirou

    Present address: Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK

Authors and Affiliations

  1. Toxicology Unit, Medical Research Council, Leicester, LE1 9HN, UK

    Maria Victoria Niklison-Chirou, Richard A. Knight, Gerry Melino & Massimiliano Agostini

  2. The Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Denmark Hill, London, SE5 8AF, UK

    Richard Killick

  3. DZNE, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany

    Pierluigi Nicotera

  4. Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, 00133, Rome, Italy

    Gerry Melino & Massimiliano Agostini

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  1. Maria Victoria Niklison-Chirou
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Correspondence to Gerry Melino or Massimiliano Agostini.

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Niklison-Chirou, M.V., Killick, R., Knight, R.A. et al. How Does p73 Cause Neuronal Defects?. Mol Neurobiol 53, 4509–4520 (2016). https://doi.org/10.1007/s12035-015-9381-1

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