Noradrenergic regulation of glial activation: Molecular mechanisms and therapeutic implications

David Braun, Jose L.M. Madrigal, Douglas L. Feinstein

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

It has been known for many years that the endogenous neurotransmitter noradrenaline (NA) exerts antiinflammatory and neuroprotective effects both in vitro and in vivo. In many cases the site of action of NA are betaadrenergic receptors (βARs), causing an increase in intracellular levels of cAMP which initiates a broad cascade of events including suppression of inflammatory transcription factor activities, alterations in nuclear localization of proteins, and induction of patterns of gene expression mediated through activity of the CREB transcription factor. These changes lead not only to reduced inflammatory events, but also contribute to neuroprotective actions of NA by increasing expression of neurotrophic substances including BDNF, GDNF, and NGF. These properties have prompted studies to determine if treatments with drugs to raise CNS NA levels could provide benefit in various neurological conditions and diseases having an inflammatory component. Moreover, increasing evidence shows that disruptions in endogenous NA levels occurs in several diseases and conditions including Alzheimer’s disease (AD), Parkinson’s disease (PD), Down’s syndrome, posttraumatic stress disorder (PTSD), and multiple sclerosis (MS), suggesting that damage to NA producing neurons is a common factor that contributes to the initiation or progression of neuropathology. Methods to increase NA levels, or to reduce damage to noradrenergic neurons, therefore represent potential preventative as well as therapeutic approaches to disease.

Original languageEnglish
Pages (from-to)342-352
Number of pages11
JournalCurrent Neuropharmacology
Volume12
Issue number4
DOIs
StatePublished - Mar 1 2014

Bibliographical note

Publisher Copyright:
© 2014 Bentham Science Publishers.

Keywords

  • Alzheimer’s disease
  • Amyloid
  • EAE
  • GFAP
  • Locus coeruleus
  • Multiple sclerosis
  • Noradrenaline
  • Review
  • Transgenic mice
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Noradrenergic regulation of glial activation: Molecular mechanisms and therapeutic implications'. Together they form a unique fingerprint.

Cite this