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Neurotoxin Modeling of Brain Disorders—Life-long Outcomes in Behavioral Teratology pp 125–152Cite as

NGF in Early Embryogenesis, Differentiation, and Pathology in the Nervous and Immune Systems

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Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 29))

Abstract

The physiology of NGF is extremely complex, and although the study of this neurotrophin began more than 60 years ago, it is far from being concluded. NGF, its precursor molecule pro-NGF, and their different receptor systems (i.e., TrkA, p75NTR, and sortilin) have key roles in the development and adult physiology of both the nervous and immune systems. Although the NGF receptor system and the pathways activated are similar for all types of cells sensitive to NGF, the effects exerted during embryonic differentiation and in committed mature cells are strikingly different and sometimes opposite. Bearing in mind the pleiotropic effects of NGF, alterations in its expression and synthesis, as well as variations in the types of receptor available and in their respective levels of expression, may have profound effects and play multiple roles in the development and progression of several diseases. In recent years, the use of NGF or of inhibitors of its receptors has been prospected as a therapeutic tool in a variety of neurological diseases and injuries. In this review, we outline the different roles played by the NGF system in various moments of nervous and immune system differentiation and physiology, from embryonic development to aging. The data collected over the past decades indicate that NGF activities are highly integrated among systems and are necessary for the maintenance of homeostasis. Further, more integrated and multidisciplinary studies should take into consideration these multiple and interactive aspects of NGF physiology in order to design new therapeutic strategies based on the manipulation of NGF and its intracellular pathways.

We wish to dedicate this review to the late Prof. Rita Levi-Montalcini, a splendid mentor and physiologist.

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Abbreviations

CGRP:

Calcitonin gene-related peptide

CIPA:

Congenital insensitivity to pain with anhidrosis

CNS:

Central nervous system

CREB:

CRE-binding protein

DRG:

Dorsal root ganglion

EAE:

Experimental autoimmune encephalomyelitis

ERK:

Extracellular signal-regulated kinase

IL:

Interleukin

MAPK:

Mitogen-activated protein kinase

NGF:

Nerve growth factor

NPY:

Neuropeptide Y

NT:

Neurotrophin

p75NTR:

p75neurotrophin receptor

PI3K:

Phosphatidylinositol 3-kinase

PKC:

Protein kinase C

PLC:

Phospholipase C

PNS:

Peripheral nervous system

SOS:

Son of sevenless

SP:

Substance P

TH:

Tyrosine hydroxylase

TrkA:

Tropomyosin-related kinase A

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Authors and Affiliations

  1. Institute of Translational Pharmacology, Consiglio Nazionale Delle Ricerche (CNR), Via Fosso Del Cavaliere 100, 00133, Rome, Italy

    Luisa Bracci-Laudiero

  2. Bambino Gesù Children Hospital, IRCCS, Rome, Italy

    Luisa Bracci-Laudiero

  3. Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Biology and Biotechnology “Charles Darwin”, University of Rome La Sapienza, Piazzale a. Moro 5, 00185, Rome, Italy

    Maria Egle De Stefano

  4. Center for Research in Neurobiology “Daniel Bovet”, Università Di Roma La Sapienza, Rome, Italy

    Maria Egle De Stefano

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  1. Luisa Bracci-Laudiero
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Correspondence to Luisa Bracci-Laudiero .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

  2. Department of Psychology, University of Gothenburg, Gothenburg, Sweden

    Trevor Archer

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Bracci-Laudiero, L., De Stefano, M.E. (2015). NGF in Early Embryogenesis, Differentiation, and Pathology in the Nervous and Immune Systems. In: Kostrzewa, R.M., Archer, T. (eds) Neurotoxin Modeling of Brain Disorders—Life-long Outcomes in Behavioral Teratology. Current Topics in Behavioral Neurosciences, vol 29. Springer, Cham. https://doi.org/10.1007/7854_2015_420

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