Grant Liska M, Crowley Marci G, Lippert Trenton, Corey Sydney, Borlongan Cesar V
Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, FL, 33612, USA.
Handb Exp Pharmacol. 2018;247:277-299. doi: 10.1007/164_2017_7.
Research of the opioid system and its composite receptors and ligands has revealed its promise as a potential therapy for neurodegenerative diseases such as stroke and Parkinson's Disease. In particular, delta opioid receptors (DORs) have been elucidated as a therapeutically distinguished subset of opioid receptors and a compelling target for novel intervention techniques. Research is progressively shedding light on the underlying mechanism of DORs and has revealed two mechanisms of DOR neuroprotection; DORs function to maintain ionic homeostasis and also to trigger endogenous neuroprotective pathways. Delta opioid agonists such as (D-Ala2, D-Leu5) enkephalin (DADLE) have been shown to promote neuronal survival and decrease apoptosis, resulting in a substantial amount of research for its application as a neurological therapeutic. Most notably, DADLE has demonstrated significant potential to reduce cell death following ischemic events. Current research is working to reveal the complex mechanisms of DADLE's neuroprotective properties. Ultimately, our knowledge of the DOR receptors and agonists has made the opioid system a promising target for therapeutic intervention in many neurological disorders.
对阿片类系统及其复合受体和配体的研究表明，它有望成为治疗中风和帕金森病等神经退行性疾病的潜在疗法。特别是，δ阿片受体（DORs）已被阐明是阿片受体中具有治疗意义的一个子集，也是新型干预技术引人注目的靶点。研究正在逐步揭示DORs的潜在机制，并发现了DORs神经保护的两种机制；DORs的作用是维持离子稳态，并触发内源性神经保护途径。δ阿片激动剂，如（D-丙氨酸2，D-亮氨酸5）脑啡肽（DADLE），已被证明可促进神经元存活并减少细胞凋亡，因此引发了大量关于其作为神经治疗药物应用的研究。最值得注意的是，DADLE已显示出在减少缺血事件后细胞死亡方面的巨大潜力。目前的研究正在努力揭示DADLE神经保护特性的复杂机制。最终，我们对DOR受体和激动剂的了解使阿片类系统成为许多神经疾病治疗干预的一个有前景的靶点。
