Multifaceted Effects of Delta Opioid Receptors and DADLE in Diseases of the Nervous System

Author(s): Jea-Young Lee, M. Grant Liska, Marci Crowley, Kaya Xu, Sandra A. Acosta, Cesar V. Borlongan*, Vivian A. Guedes

Journal Name: Current Drug Discovery Technologies

Volume 15 , Issue 2 , 2018

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Graphical Abstract:


Background: The opioid system is considered a potential therapeutic target in a variety of neurological disorders. Delta opioid receptors (DORs) are broadly expressed in the brain, and their activation protects cells from hypoxic/ischemic insults by counteracting disruptions of ionic homeostasis and initiating neuroprotective pathways. The DOR agonist D-Ala2-D-Leu2-Enkephalin (DADLE) promotes neuronal survival, mitigates apoptotic pathways, and protects neurons and glial cells from ischemia-induced cell death, thus making DADLE a promising therapeutic option for stroke. The significant amount of research regarding DORs and DADLE in the last decades also suggests their potential in treating other neurological disorders.

Methods: This review compiled relevant literature detailing the role of DORs and agonists in central nervous system function and neuropathologies.

Results: Several studies demonstrate potential mechanisms implicating a key interaction between DORs and DADLE in conferring neuroprotective benefits. A better understanding of DOR function in disease-specific contexts is critical to transitioning DOR agonists into the clinic as a therapy for stroke and other neurological diseases.

Conclusion: Evidence-based studies support the potential of the delta-opioid family of receptors and its ligands in developing novel therapeutic strategies for stroke and other brain disorders.

Keywords: Cerebral ischemia, opioids, neuroprotection, neurodegeneration, oxidative stress, hypoxia.

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Article Details

Year: 2018
Page: [94 - 108]
Pages: 15
DOI: 10.2174/1570163814666171010114403
Price: $65

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