The Noradrenergic System in Parkinson’s Disease
Front. Pharmacol.. 2020-04-08; 11:
DOI: 10.3389/fphar.2020.00435
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Nowadays it is well accepted that in Parkinson’s disease (PD), the
neurodegenerative process occurs in stages and that damage to other areas
precedes the neuronal loss in the substantia nigra pars compacta, which is
considered a pathophysiological hallmark of PD. This heterogeneous and
progressive neurodegeneration may explain the diverse symptomatology of the
disease, including motor and non-motor alterations. In PD, one of the first areas
undergoing degeneration is the locus coeruleus (LC). This noradrenergic nucleus
provides extensive innervation throughout the brain and plays a fundamental
neuromodulator role, participating in stress responses, emotional memory, and
control of motor, sensory, and autonomic functions. Early in the disease, LC
neurons suffer modifications that can condition the effectiveness of
pharmacological treatments, and importantly, can lead to the appearance of common
non-motor symptomatology. The noradrenergic system also exerts anti-inflammatory
and neuroprotective effect on the dopaminergic degeneration and noradrenergic
damage can consequently condition the progress of the disease. From the
pharmacological point of view, it is also important to understand how the
noradrenergic system performs in PD, since noradrenergic medication is often used
in these patients, and drug interactions can take place when combining them with
the gold standard drug therapy in PD, L-3,4-dihydroxyphenylalanine (L-DOPA). This
review provides an overview about the functional status of the noradrenergic
system in PD and its contribution to the efficacy of pharmacological-based
treatments. Based on preclinical and clinical publications, a special attention
will be dedicated to the most prevalent non-motor symptoms of the disease.