Title:Multifaceted Effects of Delta Opioid Receptors and DADLE in Diseases of the Nervous System
VOLUME: 15 ISSUE: 2
Author(s):Jea-Young Lee, M. Grant Liska, Marci Crowley, Kaya Xu, Sandra A. Acosta, Cesar V. Borlongan* and Vivian A. Guedes
Affiliation:Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612
Keywords:Cerebral ischemia, opioids, neuroprotection, neurodegeneration, oxidative stress, hypoxia.
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.
