Nerve growth factor: a neuroimmune crosstalk mediator for all seasons

Abstract

Summary Neurotrophic factors comprise a broad family of biomolecules – most of which are peptides or small proteins – that support the growth, survival and differentiation of both developing and mature neurons. The prototypical example and best‐characterized neurotrophic factor is nerve growth factor (NGF), which is widely recognized as a target‐derived factor responsible for the survival and maintenance of the phenotype of specific subsets of peripheral neurons and basal forebrain cholinergic nuclei during development and maturation. In addition to being active in a wide array of non‐nervous system cells, NGF is also synthesized by a range of cell types not considered as classical targets for innervation by NGF‐dependent neurons; these include cells of the immune‐haematopoietic lineage and populations in the brain involved in neuroendocrine functions. NGF concentrations are elevated in numerous inflammatory and autoimmune states such as multiple sclerosis, chronic arthritis, systemic lupus erythematosus and mastocytosis, in conjunction with increased accumulation of mast cells. Intriguingly, NGF seems to be linked also with diabetic pathology and insulin homeostasis. Mast cells and NGF appear involved in neuroimmune interactions and tissue inflammation. As mast cells are capable of producing and responding to NGF, this suggests that alterations in mast cell behaviour could provoke maladaptive neuroimmune tissue responses, including those of an autoimmune nature. Moreover, NGF exerts a modulatory role on sensory nociceptive nerve physiology in the adult, which appears to correlate with hyperalgesic phenomena occurring in tissue inflammation. NGF can therefore be viewed as a multifactorial modulator of neuro–immune–endocrine functions.

The neuroprotective effects of micronized PEA (PEA‐m) formulation on diabetic peripheral neuropathy in mice

“…It is known that mast cells release NGF (12), leading to the generation of neuropathic pain following peripheral nerve injury (25). Emerging research has emphasized the key roles of NGF in neuropathic pain conditions, although it was initially classified as a trophic factor for both sympathetic and sensory neurons during its development (52).…”

“…NGF is important in the existence and growth of specific peripheral and brain neurons. However, its elevated levels could be related to hyperalgesic events happening in tissue inflammation (12). In addition, several results indicate that DPN is not simply a disease of the peripheral nerve but is also substantially involved in the spinal cord (13).…”

Mast cell‐neural interactions contribute to pain and itch

“…Once activated, mast cells and NGF may therefore amplify each other's effects, resulting in a highly noxious microenvironment leading to uncontrolled pain. In clinical trials, NGF‐targeted therapies using NGF‐sequestering antibodies were highly successful in controlling pain, but were put on hold by the FDA because of adverse events involving the sympathetic nervous system and bones …”

“…Mast cell NGF has autocrine functions that include differentiation, proliferation, and survival. 94 Mast cells synthesize NGF by the cleavage of pro-NGF by tryptase, and upon stimulation, stored NGF is released. 95,96 In an autocrine manner, NGF stimulates mast cells to release pro-nociceptive mediators including histamine and NGF, supporting a positive feedback loop.…”

Caracterização estrutural e funcional de um fator de crescimento endotelial vascular, VEGF, da peçonha da serpente Crotalus durissus collilineatus

“…Ambos os receptores atuam em sinergismo para aumentar a afinidade dos sítios de ligação do NGF (OSIPOV et al, 2014;SKAPER, 2017 (FERRARA et al, 2003;ANCELIN et al, 2004;TAKAHASHI e SHIBUYA, 2005;OTROCK et al, 2007).…”