Ricerc@Sapienza

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons of the substantia nigra pars compacta and the brain accumulation of alpha-synuclein-positive Lewy bodies. The olfactory neuroepithelium, situated in the upper crypt of the nasal cavity, could be considered a "window to the brain". By a non-invasive nasal-brushing procedure, it is possible to collect it gently and painlessly from a broad surface area of olfactory mucosa. Therefore, the olfactory bulb represents one of the first alpha-synuclein-positive structures in the brain affected in the pre-symptomatic phase of PD, indicating this structure as one possible entry point of alpha-synuclein pathology originating in the periphery. In this area, the most vulnerable neurons seem to be the Substance P (SP) -containing neurons, which could represent an important factor involved in smell deficits observed in PD. It emerges that the SP/NK1 system could represent a target in the physiopathology and diagnosis of PD. This project aims to study olfactory sensory neurons (ONs) as potential biomarkers in PD, helping in predicting the patients with higher risk monitor the development of the disease and the effect of the antiparkinsonian therapies. We will study the expression of SP and its preferred NK1 receptor in the olfactory neuroepithelium collected by nasal brushing in control subjects, correlating their expressions to them observed in ONs acquired by PD patients of the regional Centre of PD. Since ONs contain SP, and neurotrophic factors are demonstrated to up-regulate the mRNA and secretion levels of SP in sensory neurons, a specific aim will be to characterize the expression level of SP and eventually NK1, comparing them to the levels obtained from PD corresponding control. Furthermore, to confirm the clinical data on ONs, we will perform pre-clinical experiments on an animal model of PD, obtained by intranigral injection of 6-hydroxydopamine.