Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system
Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system
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DOI：
10.1111/jnc.13447
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发表时间：
2016-10-01
影响因子：
4.7
通讯作者：
Braun, David
中科院分区：
文献类型：
--
作者：
Feinstein, Douglas L.;Kalinin, Sergey;Braun, David
除作为一种经典的神经递质参与行为调节外，去甲肾上腺素（NA）在中枢神经系统中还有其他功能。这包括限制神经炎症激活的发展，为神经元提供神经营养支持，并提供抗氧化应激的神经保护。近年来，越来越明显的是，生理NA水平或信号的破坏是多种神经系统疾病和病症的一个促成因素，包括阿尔茨海默病（AD）和多发性硬化症。在许多情况下，这些疾病失调的基础是由于蓝斑（LC）中存在的去肾上腺素能神经元的损伤，蓝斑是中枢神经系统中NA的主要来源。LC损伤存在于AD、多发性硬化症和许多其他疾病和病症中。动物模型研究表明，实验诱导的LC神经元损伤加重了神经病理学，而补偿NA耗竭或减少LC神经元损伤的治疗则有益。在这篇综述中，我们将总结NA的抗炎和神经保护作用，总结LC损伤如何加重疾病的例子，并讨论几种治疗或预防NA水平降低和LC神经元损伤的方法。进一步了解这些事件将对阿尔茨海默病、多发性硬化症和其他具有神经炎症成分的疾病和病症的治疗发展有价值。
Aside from its roles in as a classical neurotransmitter involved in regulation of behavior, noradrenaline (NA) has other functions in the CNS. This includes restricting the development of neuroinflammatory activation, providing neurotrophic support to neurons, and providing neuroprotection against oxidative stress. In recent years, it has become evident that disruption of physiological NA levels or signaling is a contributing factor to a variety of neurological diseases and conditions including Alzheimer's disease (AD) and Multiple Sclerosis. The basis for dysregulation in these diseases is, in many cases, due to damage occurring to noradrenergic neurons present in the locus coeruleus (LC), the major source of NA in the CNS. LC damage is present in AD, multiple sclerosis, and a large number of other diseases and conditions. Studies using animal models have shown that experimentally induced lesion of LC neurons exacerbates neuropathology while treatments to compensate for NA depletion, or to reduce LC neuronal damage, provide benefit. In this review, we will summarize the anti-inflammatory and neuroprotective actions of NA, summarize examples of how LC damage worsens disease, and discuss several approaches taken to treat or prevent reductions in NA levels and LC neuronal damage. Further understanding of these events will be of value for the development of treatments for AD, multiple sclerosis, and other diseases and conditions having a neuroinflammatory component.