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      Nerve Growth Factor and Pathogenesis of Leprosy: Review and Update

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          Abstract

          Neurotrophins are a family of proteins that regulate different aspects of biological development and neural function and are of great importance in neuroplasticity. This group of proteins has multiple functions in neuronal cells, as well as in other cellular populations. Nerve growth factor (NGF) is a neurotrophin that is endogenously produced during development and maturation by multiple cell types, including neurons, Schwann cells, oligodendrocytes, lymphocytes, mast cells, macrophages, keratinocytes, and fibroblasts. These cells produce proNGF, which is transformed by proteolytic cleavage into the biologically active NGF in the endoplasmic reticulum. The present review describes the role of NGF in the pathogenesis of leprosy and its correlations with different clinical forms of the disease and with the phenomena of regeneration and neural injury observed during infection. We discuss the involvement of NGF in the induction of neural damage and the pathophysiology of pain associated with peripheral neuropathy in leprosy. We also discuss the roles of immune factors in the evolution of this pathological process. Finally, we highlight avenues of investigation for future research to broaden our understanding of the role of NGF in the pathogenesis of leprosy. Our analysis of the literature indicates that NGF plays an important role in the evolution and outcome of Mycobacterium leprae infection. The findings described here highlight an important area of investigation, as leprosy is one of the main causes of infection in the peripheral nervous system.

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          Classification of leprosy according to immunity. A five-group system.

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            Nerve growth factor signaling, neuroprotection, and neural repair.

            Nerve growth factor (NGF) was discovered 50 years ago as a molecule that promoted the survival and differentiation of sensory and sympathetic neurons. Its roles in neural development have been characterized extensively, but recent findings point to an unexpected diversity of NGF actions and indicate that developmental effects are only one aspect of the biology of NGF. This article considers expanded roles for NGF that are associated with the dynamically regulated production of NGF and its receptors that begins in development, extends throughout adult life and aging, and involves a surprising variety of neurons, glia, and nonneural cells. Particular attention is given to a growing body of evidence that suggests that among other roles, endogenous NGF signaling subserves neuroprotective and repair functions. The analysis points to many interesting unanswered questions and to the potential for continuing research on NGF to substantially enhance our understanding of the mechanisms and treatment of neurological disorders.
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              Nerve growth factor: from the early discoveries to the potential clinical use

              The physiological role of the neurotrophin nerve growth factor (NGF) has been characterized, since its discovery in the 1950s, first in the sensory and autonomic nervous system, then in central nervous, endocrine and immune systems. NGF plays its trophic role both during development and in adulthood, ensuring the maintenance of phenotypic and functional characteristic of several populations of neurons as well as immune cells. From a translational standpoint, the action of NGF on cholinergic neurons of the basal forebrain and on sensory neurons in dorsal root ganglia first gained researcher’s attention, in view of possible clinical use in Alzheimer’s disease patients and in peripheral neuropathies respectively. The translational and clinical research on NGF have, since then, enlarged the spectrum of diseases that could benefit from NGF treatment, at the same time highlighting possible limitations in the use of the neurotrophin as a drug. In this review we give a comprehensive account for almost all of the clinical trials attempted until now by using NGF. A perspective on future development for translational research on NGF is also discussed, in view of recent proposals for innovative delivery strategies and/or for additional pathologies to be treated, such as ocular and skin diseases, gliomas, traumatic brain injuries, vascular and immune diseases.
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                Author and article information

                Contributors
                URI : https://frontiersin.org/people/u/554054
                URI : https://frontiersin.org/people/u/474779
                URI : https://frontiersin.org/people/u/482971
                URI : https://frontiersin.org/people/u/481812
                URI : https://frontiersin.org/people/u/383537
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                07 May 2018
                2018
                : 9
                : 939
                Affiliations
                [1] 1Center of Health and Biological Sciences, State University of Para , Belem, Brazil
                [2] 2Tropical Medicine Center, Federal University of Para , Belem, Brazil
                [3] 3Evandro Chagas Institute, Ministry of Health , Ananindeua, Brazil
                Author notes

                Edited by: Vânia Nieto Brito De Souza, Instituto Lauro de Souza Lima, Brazil

                Reviewed by: Roberta Olmo Pinheiro, Fundação Oswaldo Cruz (Fiocruz), Brazil; Esmaeil Mortaz, National Research Institute of Tuberculosis and Lung Diseases, Iran

                *Correspondence: Juarez Antônio Simões Quaresma, juarez.quaresma@ 123456gmail.com

                Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.00939
                5949531
                29867937
                24188497-9e05-4e2d-9bf1-0cce7b2ae357
                Copyright © 2018 Aarão, de Sousa, Falcão, Falcão and Quaresma.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 October 2017
                : 16 April 2018
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 76, Pages: 8, Words: 5901
                Funding
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 10.13039/501100003593
                Award ID: 302553/2015-0 and 116427/2016-7
                Categories
                Immunology
                Mini Review

                Immunology
                nerve growth factor,leprosy,mycobacterium leprae,pathogenesis,immunology
                Immunology
                nerve growth factor, leprosy, mycobacterium leprae, pathogenesis, immunology

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