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.
Graphical Abstract
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