Locus Coeruleus and Norepinephrine

Abstract

Within the next 2–3 decades, the western world will see an increase in the number of senior citizens. This increase will be accompanied by an increase incident of individuals with Parkinson's disease (PD) and Alzheimer's disease (AD), which are commonly associated with a loss of substantia nigra dopaminergic neurons and basal forebrain cholinergic neurons, respectively. Recent studies have demonstrated that noradrenergic neurons of the pontine nucleus locus coeruleus also deteriorate in PD and AD patients and that the loss of noradrenergic neurons may precede the loss of dopaminergic neurons in PD patients and cholinergic neurons in AD patients. In addition, studies on animal models have demonstrated increased sensitivity of noradrenergic neurons to neurotoxic insults. Noradrenergic neurons are thought to help regulate expression of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF), both of which are down regulated in neurodegenerative disorders. These neurons also play a potential role in regulating neuroinflammation, by reducing the production of pro-inflammatory cytokines. This article focuses on the role of noradrenergic neurons in AD and PD pathology, as well as on potential therapeutics targeting norepinephrine pathways.