Nerve growth factor: a neuroimmune crosstalk mediator for all seasons

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.