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.