The role of the locus coeruleus in the development of Parkinson's disease

In Parkinson's disease, together with the classic loss of dopamine neurons of the substantia nigra pars compacta, neuropathological studies and bioche mical findings documented the occurrence of a concomitant significant cell death in the locus coeruleus. This review analyzes the latest data obtained from experimental parkinsonism indicating that, the loss of norepinephrine in Parkinson's disease might worsen the dopamine nigrostriatal damage. Wit hin this latter context, basic research provided a new provocative hypothes is on the significance of locus coeruleus in conditioning the natural histo ry of Parkinson's disease. In particular, the loss of a trophic influence o f these neurons might be crucial in increasing the sensitivity of nigrostri atal dopamine axons to various neurotoxic insults. In line with this, recen tly, it has been shown that locus coeruleus activity plays a pivotal role i n the expression of various immediate early genes and in inducing the phosp horilation of cyclic adenosine monophosphate response element-binding prote ins, suggesting a role of the nucleus in sustaining a protective effect. (C ) 2000 Elsevier Science Ltd. All rights reserved.