Title:Noradrenergic Regulation of Glial Activation: Molecular Mechanisms and Therapeutic Implications
VOLUME: 12 ISSUE: 4
Author(s):David Braun, Jose L.M. Madrigal and Douglas L. Feinstein
Affiliation:835 South Wolcott St, MC 513, Room E720, Chicago, IL, 60612.
Keywords:Alzheimer’s disease, amyloid, review, EAE, GFAP, locus coeruleus, multiple sclerosis, noradrenaline, transgenic
mice, tyrosine hydroxylase.
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.
