Noradrenaline in Parkinsons Disease: From Disease Progression to Current Therapeutics

Francesco      Fornai; Adolfo   Bandettini   di Poggio; Antonio      Pellegrini; Stefano      Ruggieri; Antonio      Paparelli

doi:10.2174/092986707781745550

Abstract

The loss of the neurotransmitter noradrenaline occurs constantly in Parkinsons disease. This is supposed to worsen disease progression, either by increasing the vulnerability of dopamine-containing neurons or by reducing the recovery once they are damaged. Novel data also show that the loss of noradrenergic innervation facilitates the onset of dyskinesia occurring in Parkinsonian patients during dopamine replacement therapy. In the first part of the manuscript we review the evidence showing the loss of the noradrenergic system as an early event in the natural history of Parkinsonism. This evidence is discussed in light of novel reports showing the deleterious effects produced by the noradrenergic deficit on the survival of nigral dopamine neurons. In particular, we analyze the biochemical and morphological changes produced in the nigrostriatal system by the loss of endogenous noradrenaline. In a dedicated paragraph we specifically evaluate the cross affinity between dopamine and noradrenaline systems. In fact, this is critical during dopamine/noradrenaline replacement therapy in Parkinsons disease. In the last part, we overview novel therapeutic approaches aimed at restoring the activation of noradrenaline receptors to reduce the dyskinesia occurring in the treatment of Parkinsons disease.

Keywords: Neurodegeneration, dyskinesia, locus coeruleus, L-DOPA, DA agonists, D1 receptors, alpha receptors

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