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首页> 外文期刊>Progress in brain research >Neurotrophic factors and their receptors in human sensory neuropathies.
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Neurotrophic factors and their receptors in human sensory neuropathies.

机译：人类感觉神经病中的神经营养因子及其受体。

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Neurotrophic factors may play key roles in pathophysiological mechanisms of human neuropathies. Nerve growth factor (NGF) is trophic to small-diameter sensory fibers and regulates nociception. This review focuses on sensory dysfunction and the potential of neurotrophic treatments. Genetic neuropathy. Mutations of the NGF high-affinity receptor tyrosine kinase A (Trk A) have been found in congenital insensitivity to pain and anhidrosis; these are likely to be partial loss-of-function mutations, as axon-reflex vasodilatation and sweating can be elicited albeit reduced, suggesting rhNGF could restore nociception in some patients. Leprous neuropathy. Decreased NGF in leprosy skin may explain cutaneous hypoalgesia even with inflammation and rhNGF may restore sensation, as spared nerve fibers show Trk A-staining. Diabetic neuropathy. NGF is depleted in early human diabetic neuropathy skin, in correlation with dysfunction of nociceptor fibers. We proposed rhNGF prophylaxis may prevent diabetic foot ulceration. Clinical trials have been disappointed, probably related to difficulty delivering adequate doses and need for multiple trophic factors. NGF and glial cell line-derived neurotrophic factor (GDNF) are both produced by basal keratinocytes and neurotrophin (NT-3) by suprabasal keratinocytes: relative mRNA expression was significantly lower in early diabetic neuropathy skin compared to controls, for NGF (P < 0.02), BDNF (P < 0.05), NT-3 (P < 0.05), GDNF (< 0.02), but not NT4/5, Trk A or p75 neurotrophin receptor (all P > 0.05). Posttranslational modifications of mature and pro-NGF may also affect bioactivity and immunoreactivity. A 53 kD band that could correspond to a prepro-NGF-like molecule was reduced in diabetic skin. Traumatic neuropathy and pain. While NGF levels are acutely reduced in injured nerve trunks, neuropathic patients with chronic skin hyperalgesia and allodynia show marked local increases of NGF levels; here anti-NGF agents may provide analgesia. Physiological combinations of NGF, NT-3 and GDNF, to mimic a 'surrogate target organ', may provide a novel 'homeostatic' approach to prevent the development and ameliorate intractable neuropathic pain (e.g., at painful amputation stumps).
机译：神经营养因子可能在人类神经病的病理生理机制中起关键作用。神经生长因子（NGF）对小直径的感觉纤维有营养，并调节伤害感受。这篇综述着重于感觉功能障碍和神经营养治疗的潜力。遗传性神经病。已发现NGF高亲和力受体酪氨酸激酶A（Trk A）突变对先天性疼痛和无汗症不敏感。这些可能是部分功能丧失的突变，因为尽管减少了轴突反射性血管舒张和出汗，但提示rhNGF可以恢复某些患者的伤害感受。麻风神经病。麻风病皮肤中NGF的减少甚至可以解释皮肤有痛觉过敏，即使发炎，rhNGF也可以恢复感觉，因为多余的神经纤维显示出Trk A染色。糖尿病性神经病。与伤害感受器纤维功能障碍相关的NGF在早期人类糖尿病性神经病皮肤中被耗尽。我们建议进行rhNGF预防可预防糖尿病足溃疡。临床试验令人失望，可能与提供足够剂量的困难以及需要多种营养因子有关。 NGF和神经胶质细胞源性神经营养因子（GDNF）均由基底角质形成细胞和神经营养蛋白（NT-3）由基底上角质形成细胞产生：与对照组相比，糖尿病早期神经病变皮肤的相对mRNA表达显着降低（P <0.02 ），BDNF（P <0.05），NT-3（P <0.05），GDNF（<0.02），但不是NT4 / 5，Trk A或p75神经营养蛋白受体（所有P> 0.05）。成熟和前NGF的翻译后修饰也可能影响生物活性和免疫反应性。在糖尿病皮肤中减少了可能对应于prepro-NGF样分子的53 kD条带。创伤性神经病变和疼痛。虽然神经损伤的神经干中NGF的含量急剧下降，但患有慢性皮肤痛觉过敏和异常性疼痛的神经病患者显示NGF的含量明显升高。这里的抗NGF药物可能会提供镇痛作用。 NGF，NT-3和GDNF的生理学组合可模仿“替代靶器官”，可提供一种新颖的“稳态”方法来预防发展并减轻顽固性神经性疼痛（例如，在截肢疼痛的残肢处）。

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