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NGF/P75 in Cell Cycle and Tetraploidy

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Handbook of Neurotoxicity

Abstract

Neurotoxicity, neurodegeneration, and other disorders affecting neuron survival are often related to cell cycle reentry in neurons. Traditionally, cell cycle reentry of these postmitotic cells has been thought to be associated with apoptosis. Nevertheless, cell cycle reentry and DNA synthesis in neurons could also lead to tetraploidy which may explain long-lasting neurodegenerative processes. During development, a subpopulation of newborn neurons reactivates the cell cycle and becomes tetraploid in response to p75NTR activation. These neurons enlarge their cell bodies and increase their dendritic trees, thus generating specific neuronal populations that innervate particular areas. Pathological states in the nervous system could also lead to p75NTR-dependent neuronal tetraploidy. De novo tetraploid neurons might become structurally and functionally altered, thus leading to neurodegeneration at late stages of the disease. This chapter describes what is currently known about the interplay between p75NTR and the cell cycle, stressing the role played by different p75NTR interactors, including the MAGE and Bex1/NADE adaptor proteins and the transcription factors SC1, NRIF, and Sall2, in cell cycle regulation. The chapter also discusses on the effects of p75NTR, as a cell cycle regulator, in neural stem cell proliferation, neurogenesis, and neuronal tetraploidization, as well as on the connection of p75NTR in pathology, including its putative effects in neurodegeneration.

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Abbreviations

Aβ:

Amyloid-β

BDNF:

Brain-derived neurotrophic factor

Bex-1:

Brain-expressed X-linked 1

BrdU:

Bromodeoxyuridine

cdk:

Cyclin-dependent kinase

CMAGE:

Chicken MAGE

CNS:

Central nervous system

Dlxin-1:

Dlx/Msx-interacting MAGE/Necdin family protein

E2F1:

E2 promoter-binding factor-1

EGFP:

Enhanced green fluorescent protein

ERK:

Extracellular signal-regulated kinase

JNK:

c-Jun N-terminal kinase

MAGE:

Melanoma antigen

MAPK:

Mitogen-activated protein kinase

NADE:

p75NTR-associated cell death executor

NGF:

Nerve growth factor

NRAGE:

Neurotrophin receptor-interacting MAGE homolog

NRIF:

Neurotrophin receptor-interacting factor

NT3:

Neurotrophin-3

p75ICD :

p75NTR intracellular domain

p75NTR :

p75 neurotrophin receptor

PCNA:

Proliferating cell nuclear marker

PNS:

Peripheral nervous system

PR/SET:

Positive regulatory/suppressor of variegation, enhancer of zeste, trithorax

Rb:

Retinoblastoma

RGCs:

Retinal ganglion cells

Sall2:

Sal-like protein 2

SC1:

Schwann cell factor 1

SGZ:

Subgranular zone

SVZ:

Subventricular zone

TNF:

Tumor necrosis factor

Trk:

Tropomyosin-related kinase

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  1. Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, Madrid, Spain

    Noelia López-Sánchez, María Carmen Ovejero-Benito, Claudia Rodríguez-Ruiz & José María Frade

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  1. Noelia López-Sánchez
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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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López-Sánchez, N., Ovejero-Benito, M.C., Rodríguez-Ruiz, C., Frade, J.M. (2014). NGF/P75 in Cell Cycle and Tetraploidy. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_27

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