The Alpha-Synuclein RT-QuIC Products Generated by the Olfactory Mucosa of Patients with Parkinson’s Disease and Multiple System Atrophy Induce Inflammatory Responses in SH-SY5Y Cells
Chiara Maria Giulia De Luca,
Alessandra Consonni,
Federico Angelo Cazzaniga,
Edoardo Bistaffa,
Giuseppe Bufano,
Giorgia Quitarrini,
Luigi Celauro,
Giuseppe Legname,
Roberto Eleopra,
Fulvio Baggi,
Giorgio Giaccone,
Fabio Moda
Affiliations
Chiara Maria Giulia De Luca
Division of Neurology 5, Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Alessandra Consonni
Division of Neurology 4, Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Federico Angelo Cazzaniga
Division of Neurology 5, Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Edoardo Bistaffa
Division of Neurology 5, Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Giuseppe Bufano
Division of Neurology 5, Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Giorgia Quitarrini
Division of Neurology 5, Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Luigi Celauro
Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore Di Studi Avanzati (SISSA), 34136 Trieste, Italy
Giuseppe Legname
Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore Di Studi Avanzati (SISSA), 34136 Trieste, Italy
Roberto Eleopra
Division of Neurology 1, Parkinson and Movement Disorders, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Fulvio Baggi
Division of Neurology 4, Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Giorgio Giaccone
Division of Neurology 5, Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Fabio Moda
Division of Neurology 5, Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
Parkinson’s disease (PD) and multiple system atrophy (MSA) are caused by two distinct strains of disease-associated α-synuclein (αSynD). Recently, we have shown that olfactory mucosa (OM) samples of patients with PD and MSA can seed the aggregation of recombinant α-synuclein by means of Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC). Remarkably, the biochemical and morphological properties of the final α-synuclein aggregates significantly differed between PD and MSA seeded samples. Here, these aggregates were given to neuron-like differentiated SH-SY5Y cells and distinct inflammatory responses were observed. To deepen whether the morphological features of α-synuclein aggregates were responsible for this variable SH-SY5Y inflammatory response, we generated three biochemically and morphologically distinct α-synuclein aggregates starting from recombinant α-synuclein that were used to seed αSyn_RT-QuIC reaction; the final reaction products were used to stimulate SH-SY5Y cells. Our study showed that, in contrast to OM samples of PD and MSA patients, the artificial aggregates did not transfer their distinctive features to the αSyn_RT-QuIC products and the latter induced analogous inflammatory responses in cells. Thus, the natural composition of the αSynD strains but also other specific factors in OM tissue can substantially modulate the biochemical, morphological and inflammatory features of the αSyn_RT-QuIC products.