Xu Enquan, Liu Jianuo, Wang Xiaobei, Xiong Huangui
Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center Omaha, NE 68198-5880, USA.
College of Pharmacy, University of Nebraska Medical Center Omaha, NE 68198-6125, USA.
Int J Physiol Pathophysiol Pharmacol. 2017 Dec 25;9(6):165-177. eCollection 2017.
Drug abuse disorders refer to a set of related negative health implications associated with compulsive drug seeking and use. Because almost all addictive drugs act on the brain, many of them cause neurological impairments after long-term abuse. Neuropathological studies have revealed a widespread impairment of the cellular elements. As the key components to limit the damage of neural cells, CNS immune system is also found affected by these drugs, directly or indirectly. It has been shown that drugs of abuse alter neuroimmune gene expression and signaling. Growing studies on neuroimmune factors further demonstrate their indispensable role in drugs-induced neurotoxicity. As an important proinflammatory intracellular receptor, inflammasome is activated in many neurodegenerative diseases in response to a broad range of damage-associated molecular patterns (DAMPs) signals. In the cases of drug abuse, especially in those with comorbid of HIV infection and sustained pain, inflammasome activation significantly promotes the neuroinflammation-associated toxicities. To understand inflammasome in drug-associated neurotoxic activity, we reviewed the role played by inflammasome in drug abuse-induced microglial neurotoxicity and evaluated the potential of imflammasone as a therapeutic target for drug abuse disorders based on recent development of various selective small-molecular inflammasome inhibitors.
药物滥用障碍是指与强迫性觅药和用药相关的一系列负面健康影响。由于几乎所有成瘾性药物都作用于大脑,长期滥用其中许多药物会导致神经功能损害。神经病理学研究显示细胞成分存在广泛损伤。作为限制神经细胞损伤的关键组成部分,中枢神经系统免疫系统也被发现直接或间接受到这些药物的影响。研究表明,滥用药物会改变神经免疫基因表达和信号传导。对神经免疫因子的不断研究进一步证明了它们在药物诱导的神经毒性中不可或缺的作用。作为一种重要的促炎细胞内受体,炎性小体在许多神经退行性疾病中因广泛的损伤相关分子模式(DAMPs)信号而被激活。在药物滥用的情况下,尤其是在合并人类免疫缺陷病毒(HIV)感染和持续性疼痛的患者中,炎性小体激活会显著促进神经炎症相关的毒性。为了解炎性小体在药物相关神经毒性活动中的作用,我们回顾了炎性小体在药物滥用诱导的小胶质细胞神经毒性中所起的作用,并根据各种选择性小分子炎性小体抑制剂的最新进展,评估了炎性小体作为药物滥用障碍治疗靶点的潜力。