Neurotrophins in Skin Biology and Pathology

Abstract

Neurotrophins (NTs) belong to a family of growth factors, which control the development, maintenance, and apoptotic death of neurons and also fulfill multiple regulatory functions outside the nervous system. Biological effects induced by NTs strongly depend on the pattern of NT receptor/co-receptors expression in target cells, as well as on the set of intracellular adaptor molecules that link NT signalling to distinct biochemical pathways. In this review, we summarize data on the molecular mechanisms underlying the involvement of NTs in the control of non-neuronal functions in normal skin (e.g. keratinocyte proliferation, melanocyte development and apoptosis, hair growth). We also review the data on the role for NTs and their receptors in a number of pathological skin conditions (stress-induced hair loss, psoriasis, atopic dermatitis). Although additional efforts are required to fully understand mechanisms underlying the involvement of NTs and their receptors in controlling functions of normal and pathologically altered skin cells, substantial evidence suggests that modulation of NT signalling by NTs receptor agonists/antagonists may be developed as intervention modalities in distinct skin and hair growth pathologies.

p75 neurotrophin receptor mediates apoptosis in transit-amplifying cells and its overexpression restores cell death in psoriatic keratinocytes

“…12,27 In this context, we detected p75NTR in basal keratinocytes, in agreement with previous reports. Although those were mostly incidental observations in studies related to p75NTR expression in cutaneous nerve fibers or during skin pathologies, 28 our work precisely addresses p75NTR localization in human epidermis.…”

Nerve growth factor regulates the expression of vascular endothelial growth factor in human HaCaT keratinocytes via PI3K/mTOR pathway

“…High expression of NGF mediates T cell and keratinocyte proliferation, mast cell migration, degranulation, and memory T cell chemotaxis are all hallmarks of psoriasis (Nakamura et al, 2003). These findings suggest that enhanced keratinocyte NGF synthesis seems to stimulate abnormal innervation in the inflammatory skin disease (Taniguchi et al, 2007), although keratinocyte-derived NGF physiologically plays an important role in the maintenance and regeneration of cutaneous nerves in the normal skin (Nithya et al, 2003;Botchkarev et al, 2006).…”

TRP Channels and Pruritus

“…Neurotrophins significantly influence itch sensation in various pathophysiological conditions via modulating innervation density of the skin as well as expressions and/or sensitivity of receptors expressed by sensory neurons. For example, in inflammation and injuries of the skin, expression of NGF is highly increased which initiates acute sensitization and sprouting (leading to chronic sensitization) of C-type afferent fibers via activating specific TrkA receptors [87,[89][90][91]. Increased expression and plasma level of NGF were also reported in pruritic skin diseases such as in AD [92], prurigo nodularis [93] and psoriasis vulgaris [94].…”

“…Beyond sensory neuron-derived neuropeptides, neurotrophins (such as nerve growth factor [NGF], neurotrophin-3 and -4, and glial cell-line-derived neurotrophic factor [GDNF]), well-known regulators of cutaneous nerve development and regeneration [87], may also play an etiological role in the development of itch sensation and pruritic diseases. Several cell-types of the skin (e.g.…”