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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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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