الفهرس 
NeuropeptidesOnly 14 pages are availabe for public view
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Abstract
Neuropeptides are defined as a heterogeneous group of several hundred biologically active peptides with 4 to more than 40 amino acids that are present in neurons of both the central and PNSs.
In the skin, NPs are released from sensory or autonomic nerve fibers. Under physiologic circumstances, cutaneous cells such as keratinocytes, microvascular endothelial cells, Merkel cells, fibroblasts and leukocytes are also capable of releasing NPs.
The major neuronal peptides of human skin include SP, CGRP, VIP, NPY, PHM, SOM and NT.
Many trophic and immunomodulatory properties of nerve fiber and skin cell-derived NPs have been reported in health and disease. These include Keratinocytes and fibroblasts control, NPs control of cutaneous specific immune responses, NP release of cytokines from mast cells, NPs control of antigen presentation and T-cell activation and modulation of immediate and delayed-type hyper-sensitivity reactions.
In addition, some authors have claimed that cutaneous nerves decrease their rate of proliferation during the telogen phase of hair cycle and proliferate during the anagen phase.
These include CGRP nerve fibers which is a potent vasodilator that enhances blood flow during hair cycle, and SP-immunoreactive nerve fibers which are significantly increased during the early active growth phase (anagen II–III) of the hair cycle.
Strikingly, mast cells appear to change their relative preference for certain nerve fiber subtypes in a hair cycle-dependent manner. The maximum frequency of close mast cell-sensory nerve associations can be observed in early anagen, and the minimum frequency in catagen. The number of skin mast cells as well as the structural organization and the neurotransmitter/NP content of skin nerve fibers significantly fluctuate during the hair cycle.
Alopecia areata is a common type of hair loss usually presents with an oval patch or multiple confluent patches of asymptomatic, well-circumscribed, non-scarring alopecia that regrow spontaneously, but may also persist or progress to all scalp hair (AT) or all body hair, including eyebrows and eyelashes (AU).
The etiology of AA is not known exactly and its pathogensnesis is not fully understood. However, factors such as genetic predisposition, autoimmunity and stress have been suggested.
Recent research revealed that the main theory for the pathogenesis is the autoimmune mechanisms and the other theories contribute to the pathogenesis via influencing immune mediated mechanisms.
The finding of both high alexithymic characteristics and avoidant attachment in patients with AA suggests the presence of deficits in emotion regulation. Such deficits might be linked to altered physiological self regulation and possibly to psychosomatic illness, even in the absence of stressful events. Besides, there might be a complex interplay between insecure attachment, alexithymia, and poor social support in increasing the risk of AA.
It is also tempting to speculate that secreted neurotransmitters, NPs, and neurotrophins can exert hair growth-modulatory effects, e.g. by targeting epithelial stem cells in the HF bulge region. Besides, it has been established that the PNS can modulate a range of inflammatory and proliferative processes; it may be that local changes in the PNS at the level of the DP or bulge region are involved in the evolution of AA.
Neuropeptides have strong role in AA pathogenesis. Researches suggested that SP and CGRP affect the course of the disease. SP-immunoreactive nerve fibers were found to be increasing during the early stages of AA development and decreasing during advanced chronic stages. SP plays an important role in the pathogenesis of AA by interacting with distinct cellular targets in AA-affected skin. Similar to other inflammatory conditions, SP modulates neurogenic inflammation and autoimmune response in AA.
In AA lesions, the expression of CGRP was significantly diminished. AA affected HFs strongly express NEP enzyme at the margins of areas of hair loss, in the ORS possibly contributing to CGRP deficiency. CGRP deficiency in AA leads to decreased follicular basal blood flow, impaired CGRP-tolerance with autoimmune destruction of hairs, and modulation of neurogenic inflammation by mast cells degranulation. CGRP could be used for the treatment of AA but, as a neurotransmitter, CGRP could be very rapidly metabolized. Agonists with a long half-life might be more interesting.
Another NP; NGF may lead to mast cell and macrophage activation with subsequent inflammatory events leading to hair growth arrest. These effects can be abrogated by systemic treatment with anti-NGF neutralizing antibodies.
However, additional efforts employing pharmacological and genetic approaches are required to fully understand the role of other NPs in the pathobiology of autoimmune responses to HF antigens, which, eventually, may result in the development of new approaches for the treatment of AA.