الفهرس 
NeurotrophinsOnly 14 pages are availabe for public view
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Abstract
The neurotrophins family consists of four structurally and functionally related proteins: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). They exert their biological effects by binding to two transmembrane receptors: TrkR and P75NTR. TrkA is the high-affinity receptor for NGF, TrkB is the high-affinity receptor for BDNF and NT-4, and TrkC is the high-affinity receptor for NT-3.
It has been recognized that the effect of the NTs extends far beyond the horizon of classical neurobiology. In fact, NTs are now appreciated to exert bewildering array of modulatory functions outside the peripheral and central nervous systems. These include potent immunomodulatory and neuroendocrine activities. Increasing evidences suggest that NTs also regulate tissue morphogenesis, remodeling, proliferation, and apoptosis. They also control the development of kidney, tooth, muscle and heart.
The common neuroectodermal origin of the cutaneous epithelium and the nervous system makes it reasonable to hypothesize that the same growth factors that govern the development, maintenance, and axonal sprouting of neurons are also involved in skin morphogenesis and development of skin appendages. It was found that NTs are established locally in the skin by glial cells, keratinocytes, fibroblasts and merkel cells, and that NGF is critical for proper innervation of this peripheral sensory organ.
Interest in the role of NGF in human skin biology and pathology has steadily grown over the past years. Nerve growth factor is mitogenic to keratinocytes. It stimulates keratinocytes proliferation and protects them from apoptosis through binding to (Trk-A) resulting in an autocrine loop for NGF in keratinocytes. Nerve growth factor is chemotactic for melanocytes and stimulates their dendricity. In addition, NGF rescues melanocytes from UV-induced apoptosis. Nerve growth factor also regulates hair follicle development and cycling. Moreover, it is involved in the activation, migration, and proliferation of endothelial cells, lymphocytes and macrophages in the skin, as well as in the expression of adhesion molecules on endothelial cells. All these findings implicating its role in controlling the traffic of blood cells into the skin and in the promotion of a specific immune response and cytokine production with implications for chronic inflammatory, allergic and autoimmune diseases.
Increasing evidences suggest that NTs are involved in the pathogenesis of inflammatory skin diseases characterized either by cell loss (stress-induced alopecia) or hyperproliferation (inflammation, wound healing, psoriasis, atopic dermatitis) via neurogenic inflammatory processes or by inducing a misbalance in cytokine production and autoimmune responses.
Despite substantial progress in understanding the molecular mechanisms of NTs signalling during the last decade, additional efforts are required to fully understand mechanisms controlling the expression patterns of NTs, their receptors and co-receptors, as well as intracellular adaptor molecules in normal and pathologically altered skin cells. Progress in these neglected areas of skin and NTs research certainly is a prerequisite for the development of satisfactory new treatment modalities for several major pathological skin conditions, such as alopecia, psoriasis, atopic dermatitis and tumor growth, based on the well-targeted modulation of selected aspects of NTs signaling.