Laboratory for Neurodegenerative Diseases

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease associated with intra-neuronal accumulation of aggregated alpha-synuclein (α-Syn) protein, but unfortunately current knowledge still does not address the underlying pathogenic mechanisms. Consequently, PD lacks both an effective causal treatment and definitive early diagnostic criteria. In the recent years a large amount of evidence has shown that peripheral tissues like skin autonomic nerves, gastro-intestinal mucosa, salivary glands show immunoreactivity to pathogenic forms of α-Syn. Thus, peripheral tissues, that can be easily biopsied, contain nervous tissue prone to the pathology, and bear potentially important information on disease mechanisms. Our laboratory has a strong translational attitude and aims to set-up novel pathway biomarkers of disease by analyzing skin biopsy and peripheral fluids via advanced new biotechnology. Our group has published several papers on the detection/characterization of α-Syn and its pathogenic species in the skin of PD and other neurodegenerative diseases like atypical parkinsonisms plus we demonstrated that PD patients present a somatosensory small fiber neuropathy that correlates with disease duration and progression. More recently we published several papers on the specific profile of surface proteins of blood- and CSF-derived extracellular vesicles (EVs), which stratifies patients with PD and atypical parkinsonisms. These EV markers are related to circulating inflammatory and immune cells. We are now profiling prodromal and early phases of disease to identify specific signature and we are investigating how peripheral inflammation and immune dysregulation can contribute to brain neuronal cell death in PD. These projects take advantage of a biobank and clinical database for PD and atypical parkinsonisms that the PI Giorgia Melli established at NSI in Lugano since 2015.

Our laboratory is a multidisciplinary laboratory dedicated to the study of patients-derived peripheral samples (skin, blood, and CSF) by the means of advanced technology in the field of histology, biochemistry, and high throughput proteomics. We set up a proximity ligation assay, and confocal microscopy protocols for the analysis and quantification of several neuronal and aggregation prone proteins for skin biopsy specimens. We set up a standardized protocol for high resolution mass spectrometry (MS) based proteomics analysis of skin lysates. Moreover, we exploit standardized human peripheral blood mononuclear cell (PBMC) isolation and culture methods and neuronal cell lines culture protocols for the analysis of peripheral inflammation in patients with PD and atypical parkinsonisms at different stages of disease.