IMR Press / FBL / Volume 10 / Issue 1 / DOI: 10.2741/1522

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Pathobiology of dynorphins in trauma and disease
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1 Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298, USA
2 Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS 66045, USA
3 Department of Physiological Sciences, University of Florida, Gainesville, Florida USA, 32610
4 Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, S-171 76 Stockholm, Sweden
5 Pain Management Research Institute, Northern Clincal School, Department of Pharmacology, The University of Sydney E25, Sydney, NSW 2006, Australia
6 Spinal Cord and Head Injury Research Center (SCoBIRC), University of Kentucky College of Medicine, Lexington, KY 40536, USA
7 Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY 40536, USA
8 Neurobiology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
9 Integrative Neuroscience Section, NIDA IRP, National Institutes of Health, Baltimore, MD 21224, USA

Academic Editor: Rhoda Maneckjee

Front. Biosci. (Landmark Ed) 2005, 10(1), 216–235; https://doi.org/10.2741/1522
Published: 1 January 2005
(This article belongs to the Special Issue New perspectives in the therapeutic use of opioids)
Abstract

Dynorphins, endogenous opioid neuropeptides derived from the prodynorphin gene, are involved in a variety of normative physiologic functions including antinociception and neuroendocrine signaling, and may be protective to neurons and oligodendroglia via their opioid receptor-mediated effects. However, under experimental or pathophysiological conditions in which dynorphin levels are substantially elevated, these peptides are excitotoxic largely through actions at glutamate receptors. Because the excitotoxic actions of dynorphins require supraphysiological concentrations or prolonged tissue exposure, there has likely been little evolutionary pressure to ameliorate the maladaptive, non-opioid receptor mediated consequences of dynorphins. Thus, dynorphins can have protective and/or proapoptotic actions in neurons and glia, and the net effect may depend upon the distribution of receptors in a particular region and the amount of dynorphin released. Increased prodynorphin gene expression is observed in several disease states and disruptions in dynorphin processing can accompany pathophysiological situations. Aberrant processing may contribute to the net negative effects of dysregulated dynorphin production by tilting the balance towards dynorphin derivatives that are toxic to neurons and/or oligodendroglia. Evidence outlined in this review suggests that a variety of CNS pathologies alter dynorphin biogenesis. Such alterations are likely maladaptive and contribute to secondary injury and the pathogenesis of disease.

Keywords
Opioids
Neuropeptides
Neuropeptides processing
Drug abuse
Spinal cord injury
Neurotrauma
Pain
Glutamate
N-methyl-D-aspartate
AMPA
Apoptosis
Neurotoxicity
Excitotoxicity
Striatum
κ-opioid receptors
Review
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