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Revisiting the Role of Neurotrophic Factors in Inflammation

机译:再次探讨神经营养因子在炎症中的作用

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摘要

The neurotrophic factors are well known for their implication in the growth and the survival of the central, sensory, enteric and parasympathetic nervous systems. Due to these properties, neurturin (NRTN) and Glial cell-derived neurotrophic factor (GDNF), which belong to the GDNF family ligands (GFLs), have been assessed in clinical trials as a treatment for neurodegenerative diseases like Parkinson’s disease. In addition, studies in favor of a functional role for GFLs outside the nervous system are accumulating. Thus, GFLs are present in several peripheral tissues, including digestive, respiratory, hematopoietic and urogenital systems, heart, blood, muscles and skin. More precisely, recent data have highlighted that different types of immune and epithelial cells (macrophages, T cells, such as, for example, mucosal-associated invariant T (MAIT) cells, innate lymphoid cells (ILC) 3, dendritic cells, mast cells, monocytes, bronchial epithelial cells, keratinocytes) have the capacity to release GFLs and express their receptors, leading to the participation in the repair of epithelial barrier damage after inflammation. Some of these mechanisms pass on to ILCs to produce cytokines (such as IL-22) that can impact gut microbiota. In addition, there are indications that NRTN could be used in the treatment of inflammatory airway diseases and it prevents the development of hyperglycemia in the diabetic rat model. On the other hand, it is suspected that the dysregulation of GFLs produces oncogenic effects. This review proposes the discussion of the biological understanding and the potential new opportunities of the GFLs, in the perspective of developing new treatments within a broad range of human diseases.
机译:神经营养因子以其牵涉中枢,感觉,肠和副交感神经系统的生长和存活而众所周知。由于这些特性,神经营养素(NRTN)和神经胶质细胞衍生的神经营养因子(GDNF)属于GDNF家族配体(GFL),已在临床试验中评估为治疗帕金森氏病等神经退行性疾病。此外,有关神经系统外GFL功能作用的研究正在积累。因此,GFL存在于几种外周组织中,包括消化系统,呼吸系统,造血系统和泌尿生殖系统,心脏,血液,肌肉和皮肤。更准确地说,最近的数据强调了不同类型的免疫和上皮细胞(巨噬细胞,T细胞,例如粘膜相关不变T(MAIT)细胞,先天淋巴样细胞(ILC)3,树突状细胞,肥大细胞单核细胞,支气管上皮细胞,角质形成细胞)具有释放GFL并表达其受体的能力,从而导致炎症后参与上皮屏障损伤的修复。这些机制中的一些会传递给ILC,以产生可影响肠道菌群的细胞因子(例如IL-22)。此外,有迹象表明,NRTN可以用于治疗炎症性气道疾病,并且可以预防糖尿病大鼠模型中高血糖的发生。另一方面,怀疑GFL的失调会产生致癌作用。这篇综述提出了在广泛的人类疾病中开发新疗法的观点,讨论了GFL的生物学理解和潜在的新机会。

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