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.