A ROLE FOR LOCUS COERULEUS IN PARKINSON TREMOR - EXPERIMENTAL STUDIES

Although Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopamine (DA) neurons, historic and more recent anatomopathological studies documented also an involvement of the serotonergic and cholinergic systems as well as a profound loss of neurons from the locus coeruleus (LC), the major noradrenergic (NAergic) nucleus in the brain. In the following studies, I will provide preliminary evidence of a new provocative hypothesis on the significance of LC in conditioning Parkinson tremor. In particular, I speculate that, early at a disease stage, patients with PD and tremor might have an (hyper-)active LC-NAergic system, which would play a key role in the appearance of tremor itself. Furthermore, given a putative compensatory and possibly neuroprotective mechanism of noradrenaline (NA), an intact or hyper-active NAergic system would be responsible for, and support the clinical observation of, a slower disease progression in PD patients with tremor. When verified, this hypothesis will define, for the first time at a physio-pathological level, two different clinical phenotypes (i.e. tremor dominant and akinetic-rigid PD) and possibly suggest new interventional strategies (targeting the NAergic system) to modify disease progression. A number of drugs that can modulate the NAergic system already exist, ripe for testing. There is no cure for PD, and understanding the cause and progression of the neurodegenerative process is as challenging as it is necessary.