Opioid Modulation of Neuronal Iron and Potential Contributions to NeuroHIV.
Opioid Modulation of Neuronal Iron and Potential Contributions to NeuroHIV.
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DOI：
10.1007/978-1-0716-0884-5_13
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Meucci O
中科院分区：
文献类型：
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作者：
Nash B;Irollo E;Brandimarti R;Meucci O
近年来，阿片类药物的使用大幅增加，仍然是全球新的艾滋病毒感染的主要驱动因素。临床研究表明，阿片类药物可能会加剧HIV相关神经认知障碍(HAND)的症状，但阿片类药物导致认知功能下降的机制仍不清楚。我们最近报道，μ阿片激动剂吗啡增加了神经元铁水平和储存铁的铁蛋白水平，表明阿片类药物调节神经元铁稳态。此外，增加铁和铁蛋白重链蛋白是吗啡降低皮层神经元中细树突棘和蘑菇状树突棘密度所必需的，这两种树突棘分别被认为是学习和记忆的关键媒介。随着手部铁稳态改变以及阿尔茨海默氏症、帕金森氏症和亨廷顿病等相关神经认知障碍的报道，了解阿片类药物如何调节神经元铁代谢可能有助于确定与这些其他神经认知障碍潜在相关的新药物靶点。在这里，我们回顾了已知的阿片类药物调节神经元铁的机制和相应的细胞反应，并讨论了这些发现对手部患者的意义。此外，我们将讨论一种新的分子方法，该方法可以用来理解铁的阿片样调节是否影响淀粉样前体蛋白的表达和加工，以及这一途径对手部的贡献。
Opioid use has substantially increased over recent years and remains a major driver of new HIV infections worldwide. Clinical studies indicate that opioids may exacerbate the symptoms of HIV-associated neurocognitive disorders (HAND), but the mechanisms underlying opioid-induced cognitive decline remain obscure. We recently reported that the μ-opioid agonist morphine increased neuronal iron levels and the levels of ferritin proteins that store iron, suggesting that opioids modulate neuronal iron homeostasis. Additionally, increased iron and ferritin heavy chain protein were necessary for morphine’s ability to reduce the density of thin and mushroom dendritic spines in cortical neurons, which are considered critical mediators of learning and memory respectively. As altered iron homeostasis has been reported in HAND and related neurocognitive disorders like Alzheimer’s, Parkinson’s, and Huntington’s disease, understanding how opioids regulate neuronal iron metabolism may help identify novel drug targets in HAND with potential relevance to these other neurocognitive disorders. Here, we review the known mechanisms of opioid mediated regulation of neuronal iron and the corresponding cellular response and discuss the implications of these findings for patients with HAND. Furthermore, we will discuss a new molecular approach that can be used to understand if opioid modulation of iron affects the expression and processing of amyloid precursor protein and the contributions of this pathway to HAND.