Delta Opioid Receptor and Peptide: A Dynamic Therapy for Stroke and Other Neurological Disorders

Handb Exp Pharmacol. 2018:247:277-299. doi: 10.1007/164_2017_7.

Abstract

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.

Keywords: Cerebral ischemia; DADLE; Neuroprotection; Opioid receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enkephalin, Leucine-2-Alanine / pharmacology*
  • Enkephalin, Leucine-2-Alanine / therapeutic use
  • Humans
  • Nervous System Diseases / drug therapy*
  • Nervous System Diseases / physiopathology
  • Opioid Peptides / pharmacology*
  • Opioid Peptides / therapeutic use
  • Receptors, Opioid, delta / drug effects*
  • Stroke / drug therapy*
  • Stroke / physiopathology

Substances

  • Opioid Peptides
  • Receptors, Opioid, delta
  • Enkephalin, Leucine-2-Alanine