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.
Giorgia Melli MD, PhD
- Alpha-synuclein oligomers and small nerve fiber pathology in skin are potential biomarkers of Parkinson’s disease
Vacchi E, Senese C, Chiaro G, Disanto G, Pinton S, Morandi S, Bertaina I, Bianco G, Stadler C, Galati S, Gobbi C, Kaelin-Lang A, Melli G.
npj Parkinsons Dis. 7, 119 (2021). doi: 10.1038/s41531-021-00262-y
- Profiling Inflammatory Extracellular Vesicles in Plasma and Cerebrospinal Fluid: An Optimized Diagnostic Model for Parkinson’s Disease
Vacchi E, Burrello J, Burrello A, Bolis S, Monticone S, Barile L, Kaelin-Lang A, Melli G.
Biomedicines. 2021 Feb 25;9(3):230. doi: 10.3390/biomedicines9030230
- Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease
Vacchi E, Burrello J, Di Silvestre D, Burrello A, Bolis S, Mauri PL, Vassalli G, Cereda CW, Farina C, Barile L, Kaelin-Lang A, Melli G.
Neurol Neuroimmunol Neuroinflamm 2020 Aug 12;7(6):e866. doi: 10.1212/NXI.0000000000000866
- Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery Is the Core
Vacchi E. Kaelin-Lang A and Melli G.
Int J Mol Sci . 2020 Jul 16;21(14):5030. doi: 10.3390/ijms21145030
- Targeting Alpha Synuclein Aggregates in Cutaneous Peripheral Nerve Fibers by Free-floating Immunofluorescence Assay
Vacchi E, Pinton S, Kaelin-Lang A, Melli G.
J Vis Exp. 2019 Jun 25;(148). doi: 10.3791/59558.
- Cervical skin denervation associates with alpha-synuclein aggregates in Parkinson disease
Melli G, Vacchi E, Biemmi V, Galati S, Staedler C, Ambrosini R, Kaelin-Lang A.
Ann Clin Transl Neurol. 2018 Oct 14;5(11):1394-1407. doi: 10.1002/acn3.669
PUBLICATIONS IN COLLABORATIONS WITH OTHER GROUPS
- Extracellular Vesicle Surface Markers as a Diagnostic Tool in Transient Ischemic Attacks
Burrello J, Bianco G, Burrello A, Manno C, Maulucci F, Padlina G, Nannoni S, Michel P, Bolis S, Melli G, Vassalli G, Albers GW, Cianfoni A, Barile L, Cereda CW. Stroke. 2021 Oct;52(10):3335-3347. doi: 10.1161/STROKEAHA.120.033170
- Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection
Balbi C, Burrello J, Bolis S, Lazzarini E, Biemmi V, Pianezzi E, Burrello A, Caporali E, Grazioli LG, Martinetti G, Fusi-Schmidhauser T, Vassalli G, Melli G, Barile L. EBioMedicine. 2021 May;67:103369. doi: 10.1016/j.ebiom.2021.103369
Complete list of publications: https://orcid.org/0000-0003-2069-4620