What substance P might tell us about the prognosis and mechanism of Parkinson's disease?

The neuropeptide substance P (SP) plays an important role in neurodegenerative disorders, among which Parkinson's disease (PD). In the present work we have reviewed the involvement of SP and its preferred receptor (NK1-R) in motor and non-motor PD symptoms, in both PD animal models and patients. Despite PD is primarily a motor disorder, non-motor abnormalities, including olfactory deficits and gastrointestinal dysfunctions, can represent diagnostic PD predictors, according to the hypothesis that the olfactory and the enteric nervous system represent starting points of neurodegeneration, ascending to the brain via the sympathetic fibers and the vagus nerve. In PD patients, the α-synuclein aggregates in the olfactory bulb and the gastrointestinal tract, as well as in the dorsal motor nucleus of the vagus nerve often co-localize with SP, indicating SP-positive neurons as highly vulnerable sites of degeneration. Considering the involvement of the SP/NK1-R in both the periphery and specific brain areas, this system might represent a neuronal substrate for the symptom and disease progression, as well as a therapeutic target for PD.